M - HERBALNET Digital Repository

ANTI-ARTHRITIC 

DRUGS

A PRELIMINARY CONTROLLED CLINICAL TRIAL OF INDIGENOUS 

COMPOUND DRUGS IN CASES OF RHEUMATOID ARTHRITIS* 

By : 

R, H. Singh 

S. S. ~ishra 

K. M. Tripathi 

& N. S. Bhat 

ReprW from : 

Rheumatism 

Vol, 19 No. 2 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS 99

tablet8 three times a day. The patients were followed up every fortnight and the 

results were recorded on the following parameters. 

(I) Qmptomatic relief and changes in feeling of well/ill being. 

(2) The rate of shift of the grade of severity of major signs and symptoms of 

the disease rated with the help of a symptom rating scale (Table-I). 

(3) Rate of functional recovery in terms of changes in the following indices : 

(4 Walking time. 

(b) Grip power in both hands and 

(c) The pressing power measured with the help of a sphygmomanometer. 

(4) Laboratory investigations in terms of changes in haemogram and E.S.R. 

(5) Psychological assessment in terms of changes in tbe level of anxiety 

measured kith the help of Swamoolyankan prashnawali (anxiety scale, 

constructed by Dr. R. R. Tripathi of the Department of Psychology of 

'B. H. U.) 

RESULTS AND DISCUSSIONS 

The results, in cases which could be followed up for a period of three months 

are summarised in tables 2-6. The patients treated under this trial showed a 

moderate degree of improve&ent both at the level of symptoms and joint functions. 

The clinical manifestations like fatigue, malaise, fever, loss of appetite, 

canstipation, joint pain, stiffness, tenderness, swelling, soft tissue changes and 

deformities if any were found influenced by the treatment. The grades of these 

manifestations showed a minor reduction in 11 patients treated in group A. The 

e' 

I$ cases receiving trial treagment in group B showed notably better result-s 

compared to other group (Table - 2). Similarly the assessment of the functional 

status showed only a slight functional improvement in case of group A while the 

functional recovery was found more in case of group B (Table-3). The haematological 

studies revealed significant reduction In E.S.R. while the haemoglobin 

percentage and other aspects of haemogram did not show any change.(Table-4). 

In psychological assessment only 10 cases (4 in group A, 5 in group B) could 

be followed up for a conclusive duration of time. here is evidence of reduction 

in state and free floating anxiety after treatment. (Table-5). 

Thus if can be conclued that the drug Rh-1B (Rhumayoga)may have a 

moderate degree of anti-arthritic effect insubacute cases of Rheumatoid arthritis. 


Rh. 1A (AU) was tried in the dose of two tablets three times in a day in three 

patients of Rheumatoid arthritis with acute presentation for one montheach. 

These patients showed significant improvement (Table- 6) and tbe drug appears 

to be superior than the two other coded trial drugs, which did not show very good 

response in acute cases. Rh. 1A (AU) also.took a minimum of one weak to show 

respoose in acute cases. However, it appears useful and is worth trial in acute 

Rheumatism. Further extended trials are suggested. 

- - 

Sbowing Rating Scale for Symptoms of Rbeumtfslll 

1. Joint pain Absent 0 

Minor 1 

Moderate 2 

Severe 3 

2. Stiffness Absent 0 

Minor 1 

Moderate 2 

Disabling 3 

3. Swelling Absent 0 

Minor 1 

Moderate 2 

Severe 3 

4. Tenderness Absent . 0, 

Minor 2 

Moderate 2 

Marked 3 

5. Functional Disability Absent 0 

Minor 1 

Moderate 2 

Crippling 3 

6. Deformity Absent 0 

Minor & Localized 1 

Moderate 2 

Severe and Multiple 3 

- - 

SELECT RESEARCH PAYkHS ON EVIDENCE BASED AYURVEDIC DRUGS 102 

-

Observations 

Sbowing the rate of symptomrtic recovery in terms of grades of some 

systemic and local manifestation in the twe comparative groups 

Group Rh IA Group Rh IB 

Initial 15 I 2 Initial 15 I 2 

days month monfhs days month nronths 

Fatigue 1.90 1.90 1.33 1.6 2.52 1.91 2.0 1.5 

Malaise 1.90 1.80 1.33 1.6 2.23 1.72 1.9 1.5 

Fever 1.63 1.40 1.10 1.25 1.64 1.36 0.6 0.4 

Loss of appetite 1.72 1.50 1.00 0.75 1.66 1.27 0.4 0.00 

Constipation 1.63 1.21 1.W 0.50 1.70 1.18 0.6 0.5 

Joint pain ,2.45 2.10 1.66 1.75 2.82 2.36 1.6 1.0 

Stiffness 2.36 2.00 1.66 - 1.60 2.58 2.18 1.4 1.0 

Tenderness 2.10 1.70 1.44 1.60 2.47 2.18 1.2 1.0 

Swelling 1.63 1.40 1.11 1.20 2.29 1.81 1.4 1.0 

Local temperature 1.55 1.40 1.1 1 1.00 2.11 1.66 1.0 0.75 

Soit tissue 1.63 1.40 1.20 1.25 2.27 2.00 1.2 0.75 

Loss of function 1.63 1.40 1.20 1.00 2.17 1.63 1.0 0.75 

Deformities 1.00 1.00 1.10 1.00 1.00 0.91 1.0 1.0 

Muscular wasting 0.63 0.70 0.77 0.75 0.83 0.77 0.8 1.0 

Values are mean grade Scores. 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS 

103

Showing the pattern of functional recovery in the two compuati~e pomp& 

-- 

Group Rh I A Group Rh 1 B 

Functional tests Initial Follow up Initial Follow up 

Walking time in second 28.5 25.0 45.42 31.50 

Grip power in mm Hg. 

Rt. hand 

Et. hand 

Pressing ponrer in ma Hg. 

- - 

Rt. hand 58.0 63.5 49.14 72.19 

Et. hand 55.1 - 66.6 51.19 62.14 

Showing the haematological changes following treatment in two groups 

Group Rh I A Group Rh 1B 

Investigations Initial Follow up Initial Follow up 

E. S. R. in am. 4 1 .OO 32.00 35.23 21.50 


104

. 

Showipg the pattern of ebisgee is anxiety level io selected cases in the two group 

Group Rh IA. 

Anxiety 

S. No. Patient# Initial Follow up 

State Trait Free State Trait Free 

flooring floating 

1. Asha Rani Dasa 58 73 64 42 59 . 6 1 

+++ 4++ +++ -t+ ++ ++ 

2. Raj Nath 70 56 66 - - - 

+++ ++ a+++ 

3. Abrar Ahmtd 35 60 39 31 58 34 

+ +f + + ++ + 

+ +++ + 

Average 51.25 63 54.5 36.5 58.5 47.3 

+++ -t++ ++ + ++ ++ 

4. Ram khaw 42 63 49 - - - 

Group Rh 2B 

Anxiety 

S. No. Patients Initial Follow up 

State Trait Free Slate Trait Free 

floating floating 

1. Awadhesb Yadav 46 49 40 

+++ +++ + 

42 

++ 

67 46 

+++ + 

2. Banarasi Pd. 

Singh 

54 84 53 

+++ +++ + 

49 82 45 

+C+ +++ + 

3. Subhash Chandra 80 103 80 

+++ +++ +++ 

76 91 64 

+++ +++ +++ 

4. Sahodara Singh 76 63 80 74 67 82 

+++ +++ +++ +++ +++ +++ 

5. Amar Deo Cbaubey 37 5 1 57 32 47 44 

+ + ++ + + - 

Average 58.6 74 62 54.6 70.8 54.2 


Showing the pattern of shift of grades of symptom towards the betterment 

in some systemic, and locrl manifestations, and some fanction81 changes 

-by the Rh 1A (AU) h Acute Rheumatoid Arthritis cases. 

Observations Initial Follow up 

Systemic Features 

Fatigue 

Malaise 

Fever 

Appetite 

Constipation 

Others 

Local Manifestations 

Joint pai~ 

Stiffness 

Tenderness 

Swelling 

Local temperature 

Soft tissue 

Loss of functions 

Deformities 

Musclar wasting 

Functional Tests 

Walking time 

Grip power R 

5 

Pressing Power R 

L 

40 sec. 

60 mm Hg. 

70 mm Hg. 

30 mm Hg. 

40 mm Hg. 

30 sec. 

65 mm Hg. 

75 mm Hg. 

35 mm Hg. 

45 mm Hg. 


SUMMARY 

The modern treatment of Rhotubatoid Arthritb is lpostly pplliative, Certain 

indigenous drugs are suggested to W useful. Indigenous compound drugs, Rh-1 A, 

Rh-IB and Rh-1 (Au) ,were tried clinically. In tlks controlled clinical trial Rh-1B 

is found to have moderate degree of anti-arthritic effect in subacute cases of 

Rheumatoid Arthritis. Rh-l' (Au) is found to be d i in Acmte Rheumatism, 

Furqer extended trials are suggested. 


Reprint fim : 

The 

Indian 

Practitioner 

Vol. XLVl No. 12 DECEMBER 1993 Pages: 931 -941 

Cllnlcal Trlal 

Efficacy of Rhumayog and Rhumayog 

with Gold in Rheumatoid Arthritis 

- A Double.Blind Study 

U.R.K. Rao 

Addttional Professor, Dept. of Medicine, NIMS, Hyderabad 

N.S. Bhatt 

Medical Director (Ayu), Zandu Pharmaceutical Works Ltd., Bombay 

M.U.R Naidu 

Additional Professor 

T.R. Kumar 

Assstant Professor 

U.Shobha 

Senior Resident 

CPMR, NIMS. Hyderabad 

K Venubabu 

Resident, General Medicine, NlMS.Hyderabad 

Paper presented at "XVlllth (ILAR) International League Against Rheumat~sm, 

Congress of Rheumatology held at Barcelona, Span, July 1993. 

101, Lawrence Apartments 11, Vidyanagan Marg, Kal~na, 

Santa Cruz (E), Bombay-400 098 

(a 61 1 61 70 or 61 3 0329 

Ref. .. ........ GY..1.PPc2..4.C! .... 


- - 

me Indian Practitioner December 1 993 Vol. XLVl No. 1 2 

Clinical Trial 

Efficacy of Rhumayog and Rhumayog with 

Gold in Rheumatoid Arthritis - A Double 

Blind Study 

U.R.K. Rao*, N.S. I3hattQ, M.U.R. Naidu*, T.R. Kumarw*, 

U.Shobha+, K. Venubabu" 

SUMMARY 

Thirty patients (women-22, Seropositive-21) with active rheumatoid arthritis were 

studied to evaluate the efficacy of Ayurvedic products Rhumayog (Rh)) (n=:5) and 

Rhumayog with Gold (Rh Au) (n= 15) for a period of 6 months. Both drugs showed an- 

tiinflammatory and disease modifying activity. Patients on Rh showed improvement in 

articular index (A/) (p=0.001). pain index (PI) (p=0.01), walking time (WT) (p-0.05), 

ESR (p=0.01), CRP (p=0.01) and in lmrnunoglobulins (IG) (p=0.001), WT (p=0.05), E S 

R (p=0.001), Rheumatoid Factor (p=0.001) and lg levels - IgG (p=0.001), lgA (p=0.05) 

and IgM (p=0.01). However, Rh Au was better in improving the grip strength (p=0.05) 

and morning stiffness (P=0.01). No side effects were encountered with the drugs 

during the study .period. Ayurvedic preparations Rhumayog and Rhumayog with Gold 

have positive role in the management pf Rheumatoid Arthritis due to their antiinflam- 

matory and disease modfiing acivities. 

KEY WORDS 

Rheumatoid Arthritis, Rhumayog, 

DMARDS, Ayurvedic Drugs. 

INTRODUCTION 

Rheumatoid Arthritis (RA) is a chronic 

disease with uncertain aetiology affect- 

ing about 1 per cent of the population. 

Untreated deformities and/or ankylosis 

of joints will ensue with marked suffer- 

ing. Drug therapy forms the mainstay of 

the treatment which has two fundamen- 

tal objectives: 

1. Short term suppression of inflammation 

in joints which lead to lesser pain 

and greater mobility, generally 

achieved by nonsteroidal antiinflam- 

matory drugs (NSAIDs) and 

2. Long term suppression of inflammation 

which may lead to presewation of 

joint structure and function to lessen 

the likelihood of deformities which is 

achieved by disease modifying anti 

rheumatoid drugs (DMARDS)'. The 

currently used drugs in relieving the 

symptoms are not free from untoward 

side effects, the major being 

gastrointestinal. Gold salts which 

belong to the group of DMARDs are 

not without side effects but are used 

in therapy of established disease2. 

Additional Professor, Dept. of Medicine, NIMS, Hyderabad, @ ~edical Director (Ayec), Zandu Phamaceutical 

Works LM., Bombay, *Additimal Professor, *Assistant Profesx)r,'Senior Resident, CPMR, NIMS, 

Hyderabad, *+Resident, General Medicine, NIMS, Hyderabad. Paperpresentedat ';YVlllth (ILAR) 

International League Against Rheumatism, Congress of Rheumatology held at Barcelona, Spain, July 1903". 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS

December 1 993 Vol. XLVl No. 12 The lndlan Prectltloner 

Ayurvedic medicine widely practised 

in India has description of disease 

similar to RA and is claimed to offer 

treatment of the same through drug and 

non drug therapies31415 Gold prepara- 

tion in a different form as Gold Bhasma - 

a colloidal form of metalic gold- is used 

in Ayurvedic treatment for variety of dis- 

ease including RA~. 

Two Ayurvedic pharmaceutical 

preparations Rhumayog (Rh) and 

Rhumayog with Gold (Rh Au) in two ear- 

lier preliminary studies were found to ex- 

hibit a moderate degree of antiarthriiic 

In an experimental study 

Rhumayog also was observed to poten- 

tiate the antiinflammatory activity of 

other NSAlDs when used concomitant- 

ly9. 

A double blind study involving 

Rhumayog (Rh) and Rhumayog with 

Gold (Rh Au) was undertaken to 

evaluate 'the antiinflammatory and the 

disease modifying effect in patients with 

active RA. 

MATERIAL AND METHODS 

Thirty three consecutive cases with 

R A attending rheumatology services of 

Nizam's lnstiitutp of Medical Sciences 

were enrolled into the study. The diag- 

nosis of R A was based on the American 

Rheumatology Association (ARA) 

criteria1'. Each patient had thorough 

clinical, haematological, serological, 

biochemical, immunologjcal and 

radiological evaluation. The disease was 

graded according to the Steinbrocker's 

classification1'. 

Inclusion and Exclusion Criteria 

Male or female cases with R A - 

seropositive or seronegative - with morn- 

ing stiffness of more than 30 minutes 

and E S R levels more than or equal to 

30 mmllst hr. belong to the age group 

from 18-60 years were included for the 

study. 

Patients having active peptic ulcer 

disease or major systemic illness with 

renal or hepatic impairment and female 

patients planning for progeny or lactating 

mothers were excluded. Patients using 

steroids or disease modifying drugs 

such as chloroquine, auranofin, injec- 

table gold, sulfasalazine and 

methotrexate were also excluded. 

Evaluatlon Criteria 

The parameters for evaluation were 

as follows 

Clinical- Articular lndex (Al) , Pain 

lndex (PI), Loop Size (LSr) 

right, Loop Size (LSI) left, 

Grip Strength (GS) mm Hg., 

Walking Time (WT) 15 mt in 

seconds and Morning Stiff- 

ness (MS) in minutes. 

Laboratory- Haemoglobin (Hb) , 

Erythrocyte Sedimentation 

Rate (ESR), Rheumatoid 

Factor (RF) , C-Reactive 

Protein (CRP) and Im- 

munoglobulins (IgG, IgA, 

bM). 

After basal evaluation the clinical 

evaluation was done every month, the 

haematological biochemical and 

urinalysis every two months whereas the 

immunological and radiological studies 

were done at the end of 6 month 

therapy. Routine parameters including 

liver and renal function tests were also 

done at regular interyals so as to notice 

any untoward effects. 

A case record form specially designed 

for the study was followed. 

-- - 


The Indian Practitioner December 1 993 Vol. XLVl No. 12 

The medicines coded as Rh-1 and in group Rh-2 belonged to functional 

Rh-2 were supplied in the identical cap- class II or Ill and anatomical stage II or 

sules to the randomised patients in a Ill. 

daily dose of 4 capsules (500 mg each) 

three times a day in a weekly packing 

which was specially prepared for the 

study. No concomitant therapy such as 

aspirin, naproxen, diclofenac or 

ibuprofen were allowed. A provision for 

record of any other illness during the 

period study and that Of any 

effect were in the case record form. 

In the Rh-1 group statistically significant 

improvement was observed in Al 

(P

December 1 993 Vol. XLVl No. 12 The Indian Practitioner 

DISCUSSION A steroidal moiety isolated from gug- 

Ayurvedic durgs are claimed to have 

beneficial effects in the treatment of 

Rheumatic disorders. Many of these 

drugs have Guggulu- gum exudate of a 

plant Commiphora Mukul, is the main irt- 

gredient. Purified, steroidal fractions of 

Guggulu show a marked inhibition of 

platelet aggregation by ADP, Adrenalin 

and Serotonin, the effect being com- 

parable to that of clofibrate14. 

gulu the main component of Rhumayog 

was found to be more potent than 

hydrocortisone in inhibiting the severity 

of the secondary lesions in the animal 

model of adjuvant atthritis12*". Guggulu 

is always prescribed together with 

Maharasnadi quath in the Ayurvedic 

practice. The quath possess a mild an- 

tiinflammatory activity (Sharangdhar 

Samhita Part 2, Chapter 2). The exact 

mechanism of their beneficial action is 

not yet fully known in terms of bihemi- 

wl prameters16 

The steroidal component of fraction A 

of the petroleum ether extract has Rasnadi Quath, another component 

marked antiarthritic effect, comparable to of Rhurnayog, has Rasna (Pluchea lan- 

that of hydrocortisone, anq more potent ceolate) as main ingredient. The an- 

than ~henylbutazone'~. " tiinflammatory potential of some 


13. 

14. 

The Indian RaotWoner December 1993 Vd. XLVl No. 12 

IgA (mg/l) 

IgM (mg/l) 

Ayu~edic formulations containing b j Rhumayog is considered to be anal- 

the Pluchea lanceolate extract was gesic and antiinflammatory 

tested on experimental Arthritis and where as Rhumayog with gold has both 

granuloma pouch. This showed marked antiinflammatory activity and disease. 

antiinflammatory activii in both modifying property. Antiinflammatory ac- 

rn~dels'~. tivity is measured by the reduction of 

Although remission induced by gold 

therapy may be associated with better 

immuno regulation and suppression. of 

inflammatory activity, it is unclear 

whether this reflects direct ahion of gold 

on the disease itself or epiphenomena. 

Gold has been shown to alter the 

humoral immunity, complement sys- 

tems, lymphocyte, monocyte and 

neutrophil activitiesf8. 

1 582.26 + 291.47 484.86 + 292.46 

267.2 + 84.64 

185.46 + 58.1 8 

pain and swelling of joints, reduction of 

severity and duration of morning stiiness 

and improvement in grip strength 

and walking time. The disease modifying 

property is guazed by reduction of acute 

phase reactants as well. They include 

ESR and CRP". Progressively decreasing 

acute phase reactants with improvement 

in clinical parameters denote 

regression of rheumatoid disease activlty. 

This was 0bse~Bd in both groups 


2.46 

5.9 

0.05 

0.01 

113

December 1993 VQI. XLVl No. 12 The lndlan Practitioner 

X CHANCE 

o\ 

RHUMAYOG IN RHEUMAT010 ARTHRITIS 

CLINICAL : ARTlCULAd INDEX 

-10 - \< - - -- - -- - 

-- __- - _ ._ - I -_I_-- 

--- -- -0- 

i 

-- -% 

- - -- -- - - . 

-50 -- - - -- - --- - - -- -. - - - - - - - - 

-80 0 1 2 3 4 5 6 

Fig. 1 -a-- RHUMAYOG-NO GOLD _ +RHUMAYOG 

MONTHS AFTER TREATMENT 

-WITH GOLD 

'RHUMAYOG IN RHEUMATOID ARTHRITIS 

CLINICAL : PAIN INDEX 

. -..... .. .. - . . ---.I -- 

I 

- - -- 

, , 

. . 

-30 .- -- 2- 

60, - -. - -A- - -..-- ----- -- 

40 - ---.. -.--- - --- - - -.- ----- --..- - --- 

-70 

, 0 1. 2 3 

~ig. 2 

.. . . 

I I I I I 

4 ' - 5 ~ 

MONTHS, AFTER TREATMENT 

-P- RHUMAYW&O GOLD +RHUMAYOG -WITH GOU) 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS 114 

.. 

1 

6 

- 

i

The Indian Practitioner December 1 993 Vol. XLVl No. 1 2 

RHUMAYOG IN RHEUMATOID ARTHRITIS 

CUNICAL : MORNINQ STIFFNESS (MIN) 

--_ .-. 

- - - - Q- ... --- . . 

-60 ---- - " -.-- -.- -.... -. 

-80 I I 1 I I 

0 I 2 3 I 5 6 


Fig. 3 -0- RHUMAYOG-NO GOLD +RHUMAYOG -WITH GOLD 

-10 

-20 

-33 

-40 

-50 

-80 

Fig. 4 

5 CHANCE 

0 ..- -. 


CUHICAL : WALKING TIME (SEC) 

v,---i3.. 

- --. 

-. 

---.. 

..- +.:> ..:.-. . . . - - - - . . . . - - . - 

- - - -, 

'\ --a 

. 

- - - - - . .. - -. - -- ____.=- , . - - . - - 

3.. . 

--.-\.- 

- - - - - - - - -. - - -- - - -- . --- - , -.. 

7 a*-.. ' 

$ '--- *-- , - - 

- -- ---. - - . . 3 - -- -- - - . . -- - 

* I 1 1 \ I I 

0 1 2 3 -1 5 6 


-a-- RHUWYOGNO GOLD +RHUMAYOG -WITH GOLD 


'2.

December 1993 VOI. XLVl NO. 12 The Indian Practitioner 

X CHANGE 

120 

100 - 

80 - 

5 OHANCE 

zoo -. 


CLINICAL : GRIP STRENGTH (RIGHT) 

150- .- . . 

100 - -- 

Fig. 58 

RHUMAYOG IN RHEUMATOID ARTHRlnS 

CLINICAL : GRIP STRENGTH (LEFT) 

60 - . - - - - -. - - 

40 

- --- - 

- .- - - - 

I I I 

-20 - 

: 

0 I 2 3 1 5' 6 


Fig. 5A -+- RHUMAYOG-NO GOLD +RHUMAYOG -WITH GOLD 

/-a' 

;&:-L- _ - - ..---- 

I I 

0 1 2 3 4 5 (3 

MONTHS -AFTER TREATMENT - 

-a--- RHUMAYOG-NO GOLD ARHUMAYOG -WITH GOLD 


, 

I

The Indian Practitioner December 1993 Vol. XLVl No. 12 

: CHANCE 

1. 

-3 - 


CLINICAL : JOINT CIRCUMFERENCE (LEFT) 

-4 ' I I 

0 1 2 3 4 5 6 


Fig. 6A -fl-- RHUMAYOG-NO GOLD ARHUMAYOG -WITH GOLD 

X CHANCE 

RHUMAYOG IN RHEUMATOID ARTHRIIS 

CLINICAL : JOINT CIRCUMFERENCE (RIGHT) 

I U 

, . - 

.._ .- 

-2 - --- - ----- - --- -- 

-,a. 

- -- - .... _ - - r3 

-3 - --- --- --- -. -. --- 

-4 

- - ---- ------- ---- -- - --. -- -- 

-5 I I I I 

0 1 2 3 4 5 6 

Flg. 68 


-0- RHUMAYOENO GOLD +RHUMAYOG -WITH GOLD 


117

December 1993 Vol. XLVl No. 12 The Indian Practitioner 

-20 - 

z CHANGE 

-30 - - - - - -.- 


CLINICAL : ESR (mm;lhour) 

-40 - - - - - - -- -" . -- --- 

-50J 

0 2 I 6 


Fig. 7 -a-- RHUMAYOG-NO GOLD- +RHUMAYOG -WITH GOLD 

-1 0 

X CHANGE 

0 

-2 0 

-3 0 

40 


IMMUNOLOGICAL PARAMETERS 

% CHANGE AT THE END OF TREATMENT 

-50 

ROSE W U R TEST IgG (mg/L) (nW/L) IN (mi3 L) 

Fig. 8 


-0--- RHUMAYOG-NO GOLD -CRHUMAYOG -WITH GOLD 

SELECT RESEARCH PAPERE '2N EVIDENCE BASED AYURVEDIC DRUGS 118 

J

The Indian Practitioner December 1993 Vol. XLVl No. 12 

taking Rhumayog or Rhumayog with 

gold. Though the latter was better in irn- 

proving morning stiffness and grip 

strength and reducing RF titres there 

was no statistically significant difference 

in both groups. 

Treatment complication .are well 

known with established DMARDs such 

as gold salts2' and NSAlDs such as 

aspirin, ibuprofen and indomethacin2'. 

In the present study both the drugs did 

not elicit any side effects. 

CONCLUSION 

Both ayurvedic preparations 

Rhumayog and Rhurnayog with gold 

were found to be efficacious and safe in 

the management of RA. It requires fur- 

ther studies involving larger group for 

longer periods. 

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Sledge CB (Ed) Text book of Rheumatology 

WB Saunders Co, Philadelphia 1989: 982-92. 

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~ingh RH, Mishra SS, Tripathi KM , Bhatt-NS; 

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Arora RB et al. Isolation of crystalline 

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and its antiinflammatory activity. Ind J 

Exp.Bid 1979,9: 403. 

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Master, L. et al: Planta Med. 1979 : 37: 367. 

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Dhure Sons Pvt. Ltd. Calcutta 1958:444. 

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Gordon DA. Gold Compounds. In Text book 

of Rheumatology Kelley WN, Harris ED, 

Ruddy S, Sledge CB (Ed), W B Saunders Co. 

Philadelphia 1989,804-23. 

Bull BS, Westengard JC, Farr M, Bacon PA, 

Meyer PJ. Staurd J. Efficacy of tests used to 

monitor rheumatoid arthritis. Lancet 1989, 2: 

965-67. 

Husain Z, Runge LA. Treatment complica- 

tions of rheumatoid arthritis with gold, 

hydroxychloroquine, D-pt ~icillamine and 

levamisole. J. Rbeum 1090, 7:825. 

Paudus HE. on steroidal antiinflammatory 

drugs. In the Text book of Rheumatology.1 

Kelly WN. Harris ED, Ruddys, Sledge CB 

(Ed) W B Saunders Co., Philadelphia 1989, 

770-71. 


119

Reprint fiom 

The 

Indian 

Practitioner 

Vol. XLVll No. 6 JUNE 1994 Pages: 489-502 

Drug Action 

Study of Ayurvedic Drugs in Rheumatoid 

Arthritis Compared to Auranofin 

Chandrasekaran A.N. 

Professor and Head 

Porkodi R. 

Asst. Professor 

Radhamadhavan 

Addnl. Professor 

Parthiban M. 

Biochemist, Department of Rheumatology, 

Madras Medical College and Gevernment General Hospital, 

Madras-600 003 (India) 

Bhatt N .S. 

Medical Director (Ayu), Research Division, 

Zandu Pharmaceutical Works Ltd., Bombay400 025 (India) 

101, Lawrence Apartments-ll, V~dyanagan Marg, Kalna, 

Santa Cruz (E), Bombay-400 098. 

0 61 1 61 70 or 61 3 0329 


-.

June 1994 Vol. XLVll No. 6 The Indian Practitioner 489 

Drug Action 

Study of Ayurvedic Drugs in Rheumatoid 

Arthritis Compared to Auranofin 

Chandrasekaran A.N.*, Porkodi R.*, Radhamadhavanm 

Parthiban M.*, Bhatt N.s.@ 

SUMMARY 

In a randomised double blind clinical study two Ayurvedic drugs were compared for 

their DMARD potential with Auranofin in Rheumatoid Arthritis. 

60 patients with definite RA were randomly allocated into Group A (Ayurvedic 

Drug), Group B (Rhumayog with Gold), and Group C (Auranofin) and studied for a 

period of 6 months. 

Clinical and laboratory parameters including Serum Gold levels were assessed peri- 

odically and analysed statistically by Wilcoxon's signed Rank Test and Friedman's Test 

for Trend. 

Female to male ratio was 18:2, 17:3 and 18:2 and the average age in years were 

39.15,38.75 and 34.90 in respective groups. 

Group A drug showed a statistically significant improvement in Ritchie lndex (0.006) 

duration of morning stiffness (0.008) platelet aggregation (0.19) sero conversion 

(0.012). Group I3 drug showed statistically significant improvement in Ritchie lndex 

(0.001) and plstelet aggregation (0.000). Group C drug showed statistically significant 

improvement in Ritchie lndex (0.000), no. of joints involved (0.000) duration of morning 

stiffness (0.0 13), walking time (0.020) and platelet aggregation (0.000). 

It is concluded that there is a disease modifying effect in group A (Ayurvedic Drug) 

as in Auranofin. 

KEY WORDS whereas DMARDS have marrow, renal 

Rheumatoid Arthritis, Rhumayog, and hepatic 

DMARDS, Ayurvedic Drugs, ~uranoin.~ 

Ayurved, the ancient system of 

INTRODUCTION medicine, is practised in. Indian sub- 

Rheumatoid arthritis is a chronic in- continent for' many centuries and 

flammatory disorder due to inflammatory several drugs are used for the treat- 

mediators generated by immunocom- ment of rheumatoid arthritis, a disease 

petent cells during the process of which is described as ~mavaata*. Not 

elimination of the hypothetical antigen only anti inflammatory drugs are used 

from the system. While drugs are avail- but also gold preparations in the form 

able to ameliorate the symptoms due to of Gold Bhasma. have been widely 

inflammation in the form of NSAIDS, the used3. In the modein system of 

long term suppression is achieved by medicine gold is used in the form of 

the DMARDS' . Most of the ' NSAIDS gold salts. The goid used in Ayurvedic 

have gastrointestinal side effects system is in a colloidal form. 

*Professor and Head, -Asst. Professor -Addnl. Professor, -Biochemist, Depattment of Rheumatology, 

Madras Medical College and Government General Hospital, Madras 600 003 (India) 

@~edical Director (Ayu), Research Division, Zandu Pharmaceutical Works Ltd., Bombay 400 025 (India) 


121

The Indian Practitioner June 1994 Vd. XLVll No. 6 

The two Ayurvedic drugs were found 

to be effective in preliminary clinical 

studies4". It was therefore decided to 

compare the efficacy of these two Ayur- 

vedic drugs, one corisisting of Guggulu 

extracted in Triphala water and the other 

Rhumayog with Gold with Auranofin an 

existing DMARD in a randomised double 

blind study. 


68 patients fulfilling the ARA criteria 

for the diagnosis of RA were included in 

the study. The patients were randomly 

allocated into groups A,B, and C. It was 

decided to have minimum 20 completed 

cases in each group for better comparison. 

8 patients dropped out and 

remaining 60 formed the comparative 

groups. The period of study was from 

December '89 to June '92. 

The drugs were administered in the 

form of capsules of 500 mg each in the 

dose of 4 capsules three times a day. 

The dose of comparable drugs being 

quite different administration required 

special packing as follows: 

Group A: Ayurvedic Drug (Guggulu 

extracted in Triphala water) 

Each Capsule contains 500 

mg. of the above extract. 

Group 6: Morning dose - 3 caps. of 

Rhumayog with gdd 

corresponding to 1 mg of Gdd 

in each and 1 cap of plain 

Rhumayog. Noon and evening 

doses - plain Rhumayog. 

GroupC: Morning dose - 2 caps of 

Auranofin (3 mg each) and 2 

caps of placcL,a. 

Noon and evening doseplacebo. 

Inclusion and Exclusion Criteria 

Patients above the age of 18 years 

suffering from active rheumatoid arthritis 

and who consented to ,comply with the 

therapeutic schedule were included in 

the study. 

Patients with other connective tissue 

disease and with clinically manifest abnormal 

test function of heart, lungs, liver, 

kidney or those with endocrinological or 

neurological distrurbances or those 

having haematological or psychiatric disorders 

were excluded from this study. 

Patients having malignant tumours were 

also exluded. 

Evaluation Criteria 

The following criteria were followed: 

Clinical: 

1. Ritchie Index 

2. Number of Joints involved 

3. Circumference of the proximal interphalangeal 

joints 

4. Duration of morning stiffness 

5. Grip strength 

6. 50 feet walking time 

7. Functional class by Steinbrocker's 

classification 

Laboratory parameters 

Haematqlogical: Complete Haemogram, 

Platelet aggregation, B.T., and 

C.T., P.T. were studied. 

Biochemical Parameters: Hepatic 

and renal toxicity, Blood sugar, 

Cholesterol and Serum cortisol levels 

were studied. 

immunological Parameters: RA factor 

both by Rose Waaler and RF Latex 

Agglutination methods as well as important 

markers CRP, ANA IgA, IgM, 

IgG, C3 and C4. 

Serum Gold levels were specifically 

studied. 

Urine analysis- Complete urine 

analysis, creatinine clearance, protein 

excretion fbr 24 hours. 

SELECT RESEARCH PAYERS ON EVIDENCE BASED AYURVEDIC DRUGS 122

June 1994 Vol. XLVll No. 6 The Indian Practitioner 491 

Radiological Changes: X- rays of the 

involved joints were'taken. 

U@e Analysis, 

lmmunolog ical - Basal and every 

Time schemes for evaluation was as 

follows: Radiological 

two months 

- Basal and at the 

end of the study. 

General followup 

and drug supply - Every week 

Patlent Consent 

Informed consent of the patient was 

Clinicel assessment - Basal and every obtained in writing before administering 

fortnight the trial drug. 

Haernatological 

and biochemical - Basal and 

RESULTS 

CLINICAL TRIAL ON R~UMAYOG IN 

every month RHEUMATOID ARTHRITIS 

Age Range 

Mean Age 

Female 

Male 

Group A 

27.60 yrs. 

39.15 yrs. 

18 

2 

Table 1 

Parameter: a. Age 

b. Sex 

Group B 

18-57 yrs. 

38.75 yrs. 


17 

3 

Group C 

20-52 YW. 

34.90 yrs. 

18 

2 

123

The Indian Practitioner June 1994 Vol. XLVll No. 6 

Parameter: Total no of Joints 


June 1994 Vol. XLVll No. 6 The Indian Practltloner 493 

Friedman's test for trend 0.046* 

Total 15 S 20 15 5 20 19 1 20 

Improved 

Deterlorated 

P. Value 


2 

2 

NS 

4 

3 

NS 

Signj.'(P=O.OS) 

I 

7 

0

The Indian Practitioner June 1994 Vol. XLVil No. 6 


June 1994 Vol XLVll No. 6 The lndlan Practitioner 4&1 

Friedman's test for trend .225 ns 

Group C 

Mean 

Wilcoxon's signed rank test 

Friedman's test for trend 

59.50 

- 

57.50 

..678 ns 

:I 63 ns 

62.30 

.308ns . 


66.00 

.485 ns 

127

The Indian RactRloner 

June 1994 Val. XLVll No. 6 


June 1994 Vol. XLVll No. 6 The Indiah Practitioner 

Drug Group 

Group A 

Mean 

Wllcoxon's s~gned rank test 

Frledrnan's test for trend . 

Group B 

~ean 

Wtlcoxon's slgned rank test 

Fr~edrnan's test for trend 

Group C 

. Mean 

Wilcoxon's slgned rank test 

Fr~edrnan's test for frend . 



Group C 

Mean 

W~lcoxon's s~gned rank test 


' 

'I 

Table 15, 

Parameter: lgGU IU/ML 

Months after treatment 

0 4 

1 2 I 1 6 

275.00 

- 

284.95 

- 

,277 40 

- 

- 

257.00 

- 

0.829 ns 

295.25 

,433 ns 

,337 ns 

283.60 

.760 ns 

,420 ns 

259.90 

.695 ns 

,815 ns 

.091 ns 

,090 ns 

289.60 

0.571 ns 

281.45 

.673 ns 

281 35 

,794 ns 

248.60 

,463 ns 

,167 ns 

273.85 

0.5?6 ns 


306.95 

,205 ns 

298.75 

,478 ns 

255.75 

.519 ns 

.968 ns 

2d.50 

0.570 ns


Drug Group 

Group A 

Mean 

Table35 

Parameter: C 3 Mglml. 

Months after treatment 

Wilcoxon's sianed rank test 

.480 ns .407 ns .705 ns 

I Friedman's test for trend I I .605ns I I I 

I Group B I 

Mean 

Wilwxon's signed rank test 


I Group C 

0 

1 1 58.75 

- 

I Mean [ 1314.50 1 1113.00 1 1068.00 '1 1148.50 1 

- 

- -- 

Wiicoxon's signed rank Jest 




Qroup C 

Mean 

Wilwxon's signed rank test 


10086.40 

- 

.749 ns 

- 

431.55 

- 

.2% ns 


2 

1131.00 

11 76.50 

.409 ns 

.721 ns 

.248 ns 

.844 ns 

.693 ns 

392.05 

.064* 

4 

1116.40 

1171.00 

.825 ns 

.I70 ns 

.981 ns 

392.30 

.259 ns 

6 

1023.50 

1200.00 

.747 ns 

.067 ns 

.602 ns 

443.40 

.687 ns 

'

Rheumatoid arthritis is -an inflam- 

-- 

bpu#shef+found to have 

antiinflammatory effects". The steroidal 

constituents of guggulu may be respon- 

sible for the antiinflammatory action. 

Iey ac y In I I lng p a e e aggrega- 

t- ni bCt 9CM3R29t -6 xarrdi 

sqt-l& k~ rrsiarcsludprzGra4wd b@ 

was ~~rnb~tlB~dd,nhf 

t&@q!& 

~st%ta~dn%dP &w &its m q w g 

ri;fit W~o"bkc9hj 

~i!$iW%gk$&!Q 

'Mf6@1 '$Sif;n&~~~Fti6~Su~ 

fertWi&W%R @fWri#B@ifiQQ%~i! bsrl 

-mt nwode bsrl zjnsl:sq '3 .l:ss~tlne~z 

"%hu#P~%)agiSlad~9flbwflIa IltYME81a 

~y significant irRij?6HW~F 9fid R i W 

Writ xebd~pr~wftmmt 

nt intnsnt$%~ 

pqpWsreJJ ~bn#W~o~afLst~ba~@~ 

-mg@tb Wl~mplpvaC);m 

s l r w l u v r , & ~ E B l ~ ~ ~ - ~ r n 

sbtMiml;rCI s W i W Mprmmllbttf),


x CVCE 

10 

AYURVEDIC DRUG / AURANOFIN IN 

RHEUMATOID ARTHRITIS 

ESR (mm/hr) 

-30 - . -- . . - - - &-.-.--&L- 

*. .. .' 

-40 

".*= 

I I 1 I 1 

0 1 2 3 4 S 6 


AWRVEDIC DRUG -!- BBWYOO-rn [W)U '*. AUP*WOm 

Latex aggutination test. The fall in the 

CRP levels also showed EL statisticdlly 

significant trend by Friedman's test, 

The ESR had also shown a fall at 

the end of the trial though not statisti- 

cally significant. Similarly IgM levels 

had shown a fall though not statistic811y 

significant. 2 patients had shown irn- 

provement in their functional class 

while 2 had deteriorated. 

Group 6 drug (Rhumayog with Gold) 

showed a statistically significant im- 

provement in Ritchie Index and 

Friedman's test for trend wes also sig- 

nificant. 4 patients hed shown improve- 

ment in'their functional class white 3 had 

deteriorated. In the , I@ paraineteq 

, platelet aggregation 8howqta signiflm 

irriprovement by Friedman's test: The fdl 

in ESR was not statistical@ slgnifkant. 

Similarly the fa! in the Rheumatoid Factor 

titres was also not significant though 

5 patients had become sero negative by 

Rose Waabr t?t.and two patients had 

became seroi .negative by latex agglutination 

t ~ tthe d end of ihe trial. 

Group -'C drbg (Auranofin) in the 

present also'showed a significant impmvment 

in . several clinical 

. parameters like Ritchie Indw, No. of 

joints Mvolved, duration of morning 

stiiess and walking' time. The 

Friedman's test for twnd was also siggnificant 

faf all these parameters. 

Thefe was a remarkable improvement 

in the functional elks. 7 patients had 

improved while non had deteriorated. 

In WLeb paramatp. ESR had f how 

a'fall. a8 shoyn by the Friedmq'a test 

for trend: Platelet' .aggcegruti& had 


June 1 994 Vd. XLVll No. 6 The Indian Practitioner . . 

AYURVEDIC DRUG / AURANOFIN IN ! 

RHBUMATOID ARTHRITIS 

ROSE WAALER TEST 

I 

-60 i' 

0 1 

I 

2 

I 

3 

1 

4 

I 

5 6 


i- AWRVEDIC DRUG RBUYAYOG-WITE GOLD -". AURANOPIN 

shown a significant fall Sero conversion 

by Latex aggultination while 4 had be- 

come negative by Rose Waaler test. 

A unique feature in this study was the 

estimation of Serum gold levels. 

Patients who were on Group C drug 

namely Auranofin showed a significant 

level ranging from 10.63 to 2077.50 

nonograms, while patients on Group B 

drug namely Rhumayog with Gold had 

lower levels ranging from 1.50 to 457.5 

nonograms. Patients on group A, Ayur- 

vedic drug shown negligible amount of 

Gold in few cases. 

The side effects with all the three 

drugs were mild and did not necessitate 

withdrawal. The 8 dropouts were due to 

non compliance of the patients and not 

due to side effects of the drugs. 

This study confirmed our previous 

study that Auranofin has disease modify- 

ing efficacy. Among the two Ayurvedic 

Drugs Group A drugs has a definite dis- 

ease modifying tendency as evidenced 

by a fall in the levels of ESR, CRP, 

Serum IgM levels and sero conversion 

by Rose Waaler test. 

Probably the amount of Ayurvedic 

Gold (3 mg) in Group B drug was not 

sufficient to have any disease modifying 

effect, Thus this study shows that Ayur- 

vedic drug is comparable to Auranofin in 

its disease modifying property in 

rheumatoid arthritis. 

REFERENCES 

1. 0. Duffy JD, Luhra HS; Current Status of dis- 

ease moditying drugs in progressive 

Rheumatoid arthritis. Drugs 1984,27: 373-77. 


133

1% # 

The Indian Practitioner 

:2-.n:$il!)zr, ;8 r:&?rd stfl 

- AWRWDIC DRUG 4- REUU~OG-~ITH COW -*lc- AURANOFIN 

A - - moa HTW-~OYAW'JHH - wao slasaw~ - 

-- -- -- 

2 Yog Ratnakar, Aamavata chikista; Publ. 

r~QtracAmgmkeSabrtn-&rtBs orf~b&Mar&i&i 

E;WfiWer!) es;J n;tonsruA fsrif vbutz 

b~51f?!?f%3 as y,lnetnsj pni.4ibom szss 

ma192 

, : ~ j & ~ r y j m w t r i b ~ ~ j ' 1 ~ ~ 

digenous compound &q,&s~~gq yd 

Rheumatoid arthrlt~s; Rheu at~sm, . o . 

nFdP?H$%iYRldt.WisplMdsla plnb aibsv 

6. rikob@wC#ale &q&@~.~ 

011 ?'%%hid 

Arthritis; Pharma. I 19@&@&6bdOkm~9dl 

June 1994 Vol. XLVll No. 6 

a .OH !IVJX .IOV pee t snuL 

8. Chandrasekaran AN. Ramakrishnan S, Rad- 

nbanedhnmro~C8antR6~aia~~~dz 

ces Academy 1989, Vol. 2, No. l,21-25. 

zs 63 gt ni bioa 

11. Bhatt N S; Review of ~yirve%c ~#tnlcal Re- 

7. Manthrope R, Horbov S, S lvest J, sod 

Vinterharg H; Auranofin Vs & w d ~ ~ f l 

00WiuJla?Bi&QMT3116Wri#w 

%&V@l.%b' . r 

c~uib ~niytiborn szse I 2. ja~~~~dkre da~1)8qtaWo1 d j w 3 non 

IT-CTE :TS ,&Bet a~uiCJ .eitiidfis biotsrnusdR 

.eeuib srlt to ej39tf9 sbie ot sub 

-.-"- - .- ----- . -.".- 


134 

rE h 

23URU 31a3VRU'llA a3ZA8 33MRUIV3 MO 21I34AP H3RA323R T33J32

-- 

OPEN STUDY TO EVALUATE THE EFFICACY OF SALLAKI AS AN ADD-ON 

NSAM).CN ,THF M4W4CirF;rMFNT ,OF! PATIRN,TS F1. LTH 

* Author for correspondence 

Dr. A. Rajadhyaksha M.D. 

Assoc. Prof. in Medicine 

K.E.M. hospital, Parel, Mumbai - 400 0 12 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVED~C-DRUGS 

f33

ABSTRACT 

In a double blind, randomized parallel grobp study, forty-seven patients with classic or 

definite rheumatoid arthritis were treated with SallakiO (600-mg t.i.d) or Diclofenac sodium 

(50-mg t.i.d). The duration of the treatment period was four weeks. An interval of five days 

was established as a washout period. Paracetamol tablets were used as rescue analgesics 

during the washout as well as the trial period. The following variables were tested: Duration 

of morning stiffness, grip strength, time to walk 50 feet, pain severity using VAS score, 

number of swollen and tender joints, degree of swelling and tenderness in the affected joints, 

digital joint circumference, paracetamol consumption, ESR and overall efficacy by the 

physician. A statistically significant improvement in VAS score, duration of morning 

stiffness, tenderness and swelling of the affected joints and a decrease in the number of 

swollen joints was observed. No statistically significant differences were found between 

SallakiB and Diclofenac sodium. ~oth the drugs were well tolerated but a trend towards 

fewer adverse reactions of SallakiQ was found. 

Key words: Diclofenac sodium, Sallaki @, Rheumatoid arthritis 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVRDIC DRUGS 136

INTRODUCTION 

Osteoarthritis is one of the most common rheumatological conditions to affect humans. In India, 

thc prevalence of osteoarthritis in adult rural population was found to be 5.78% ' . It is a leading 

cause of chronic disability in the elderly population rendering them unable to perform their daily 

routine activities independently. 

The disease represents failure of a diarthrodial (movable, synovial lined) joint and is 

characterized by degeneration of articular cartilage, hypertrophy of bone at the margins, and 

changes in the synovial membrane. The progress of the disease is variable and in some patients 

relentless, leading to end stage joint disease necessitating joint replacement. 

'The most common presentation of osteoarthritis is insidious onset of pain, stiffness and disability 

in the involved joints. Pain in and around the involved 'joints is a cardinal symptom in OA that 

typically is aggravated by joint use and relieved by rest, but, as the disease progresses, it may 

become persistent. Stiffness of the involved joint on arising in the morning or after ,a period of 

inactivity may be prominent but usually lasts less than 20 minutes Functional impairment in OA 

however is highly variable and depends on associated muscle wasting and weakness and 

correlates with the radiological severity of the disease.. 

Treatment of OA is aimed at nlinimizing pain, optimizing fbnction and reducing disab~lity 

Amongst drugs, non-steroidal anti-inflammatory drugs (NSAIDs) are most often prescribed for 

relief of pain and control of inflammation. However their use is limited bi gastric and renal 

toxicity. Elderly patients are particularly prone to develop serious NSAlD related gastrointestinal 

complications like Perforation, Ulceration, Bleeding (PUB) and death Some NSAIDs 

particularly aspirin and indomethacin . have been implicated in cartilage degeneration'and their 

use is best avoided in osteoarthritis 

The preferential cyclooxygenase 2 (COX-2) inhibitors like meloxicam that are chondroneutral, 

equally effective and with fewer side effects are thus widely employed in the management of 

osteoarthritis "4 

However the magnitude of improvement with NSAlDs is generally modest - on an average there 

5 

is 30% improvement in pain and 15% improvement in knction . This could be due to the 

inhibition by NSAlDs of only one of the mediator of inflammatio; i.e. cyclooxygenase. 

Leukotrienes, f& which the 5-lipooxygenase (5-Lox) is the key enzyme,arx ah-idvd in the 

initiation and the maintenance of inflammation. From tbefiy ~Tleukotrienes type mediators, 

leukotriene Bq is a potent stimulator a£-leukocyte responses like chemotaxis, cell adhesion, 

superoxide production, calciu~rlnslocation, and release of hydrolytic enzymes. They also 

stimulate pronounced_plasffia exudation in vivo -9 

Thus cgaedmitant administration of lipooxygenase inhibitors and cyclooxygenase inhibitors 

wmkflead to a better control of inflammatory conditions 


The gum resin exudate of Bo,weIlru serrutu used In traditional Ayurvedic ~!;?F;tk'd(aJa%kfI 

treatment of inflammatory diseases is a potent inhibitor of 5-lipooxygenase but does not impair 

thd-p~~2 a&{~#~~~~~fh~gggs'&f#tef &li&:~g~@ Hbrrt~fich? jzor11 -XI r to grir, 11 rill rrIfr~ostA. 1 

. a- "'t'i ' - 3 i * rij ,;I .I,! 1 r: ~ j ~ ~ , j *{ ~ h;i!17 : ~ * tj;j!>j: HI -~i1!11jja t>jt>~'3fb >J~I~II;'!~I~[ ?ti' 

Phaf~lugic~j~potsti$~ti~rig~~ 

@I;& i h g I kw;i.ey4ed iithfe &&I rr tpda&&;arhi4n&W&toyt) J 

agent devoid of side effects like gastro-intestinal irritation, hemorrt$gt$bkp@i& &ilmaNdio? 

electrolyte retention '-I2 A marked analgesic effect has also been reported for the drug 11 

I ,,ti6 ;:ttol (bun11 !h1,rlr1/2 .3ldr;~,,m) ltihc11lf71;i0 t; 'jrj ~IIJ~II;~ ~f~13d*3i(j31 ~ZI;YZI~ 

sri'i 

E%petiwnfal $tbdiesfmddnhhl~~ lpmbd.?&&tFe3 &Wi; akhifl~ l ~ w y t r b i ~ a k s y E ~ 

rebM ai1mats t~bke3ld9treox&&di~ajMtIb1 ~ ~ i & t ' E W ~ ~ 16mf&b&dis3@113 

i t & 

spondylitis without an~:~8a~tlA-hf ~"tt"~i'L33311 szsserb tnrol ~gfild ilns oJ gnrbrcrl , ~ C ~ I $ ~ I ~ J I 

~~lthilsrrt t&iflts.?~&l~bcl~eh~ 444FIr~&~l&idatttl~&t~ 6&4@4U€&$ WW&%~M'~YWI~~ 

1 

'ndtno W tb6c~ifcrlwt~tra$PBd~~k6jl~~~rkd!~&Sih 

dhdt~%~@bpG~fkO'~#~ @d(btdi add 11 I 

:&-I l!ahk+t~j :@t~ld~tbdeti~ A1~br~dBsdr~~~fitht:3mdl~~o~d~fd~zu~fist 

!m$xitanneaAbelt$w~~~ :Jr~r:r-rom .;\rl~ rrr y!lr,irc r~o Ir11oi h311(1./r11 3df ?a PLL~I~!I!~ ~(:~!%IL-IL~c~ 3rr10;3d 

i I j $1 tY~.!nllr,il:irl l~,r!~,r~3rllf'i 23filrl18n U!: 111;111 2~41 ~t%81 ~ I ~ G U Z U flld !i19:11111L 

JIJ, 1f;f!l rflf,3it'fjb?tri 2All 

I sa\\&i ~2QRwH~dd 

IWft)vjr;dl'$ 1% IF 

51s ?irt31lt $7 ~ l i ~ i r l ~tidi~ot 

~ 2 

early cases having mild pain with no radiological 

standing disease w~th moderate to severe radiological changes it showed a fair to poor response 

~~~ b . W;H!H~P~kh~rcsitR1%t&aWfik~PAC1f~JI~rll 

?(I 1A %V .7d riotlid1 rln1 " 

19 

)I ]I! i, tti; n/h p;~$mi $1 nior:ea 21 dl lXCf ::ii J f 3rn~vi I rrlr to t)

It was conceived that if a lipooxygenase inhibitor i.e. SaIlaki and KZ~C16bti)ige"nae Zh'itjitbi i;6: 

NSAIDs were used simultaneously in the treatment of osteoarthritis a considerable jmnrouernenk 

in the pigns ,a@ symptqvs' of the ,disease wovld, probably be.achieved. 

F~*h~~~~,$"~$@~i{9~dfj;p~Ifi~ 

(-$~$~$NGI i4Fidp,&*fl; G+3Niiiif1 ~Pja~m 

of the 

s wlt a a t at 1s a so ute y free of side e ect3 would help in contaj&g,&


Patients selecti 

Consecutive pat1 !3 nts with primary osteoarthritis of the knee and/or hip (clinico-radiological 

ARA criteria) attending the rheurnatology O.P.D. at K.E.M. Hospital were enrolled into the 

study. The patients were in the age group of 18-70 years. In addition all patients included in the 

study had: 

1 history of taking any one NSAlD in adequate doses for at least past one month without 

satisfactory relief 

ii pain and/or stiffness in the knee and/or hip joints and/ or difficulty in walking and/or 

climbing 

The patients were excluded if they had undergone prior replacement surgery or were 

incapacitated or bedrhden, or eligible for surgical intervention, or had active peptic ulceration or 

prior gastrointestinal bleeding. Other exclusion criteria included cardiorespiratory insufficiency, 

significant disease of any other major organ system, allergy to aspirin or other NSAID, 

concurrent anticoagulant therapy, concurrent ayurvedic drug therapy, or recent systemic or intra- 

articular corticosteroid therapy. 

The protocol had been reviewed and ratified by the ethics committee at K.E.M. Hospital. All the 

patients gave written informed consent before enrollment into the trial. 

Study deslgn 

The study was conducted as an open trial. After the patient satisfied the entry requirements, a 

complete medical history was taken and a general examination performed. The disease activity 

was measured by' grading the pain, tenderness, swelling, morning stiffness and hnctional 

impairment for the right knee, lee knee, right hip and leR hip on a five point scale. 

The patients ihen underwent a global assessment ooMioting of an administered questionnaire. 

The questionnaire included all the thirteen physic4 function criteria of the KGMC Index, which 

is a validakd-nmdified WOMAC Index to evaluate response in Indian Patients with 

osteo&tic bee. A scoring pattern different from the one used for arriving at the KGMC 

Index was adoptid owing to the failure in obtaining the original scoring pattea. 'Ilkus the KOMC 

Index was renamed as Modified KGMC Index EorPhysical Function Criteria 

The disease activity measurements were conducted during the screening visit, at the end of the 

second week, fourth and the sixth week i.e. the final assessment. 

The physical function questionnaire was admin~stered only at the end of the fourth and sixth 

week. 

At the end of the study both the investigator and the patient assessed the overall efficacy and 

tolerability to the tre-ent. 

The patients were kd to consume Sallaki (400 mg) 1 t.i.d. along with their routinely 

prescribed NSAID. T "8, y 'were asked not to change their therapy or consume any other analgesic 

/ - 


during the study period At the 'end of the fourth week the patients were asked to discontinue 

their NSAID medication and consume only Sallaki (400 mg) 1 t.i d. for a period of additional 

two weeks 

At every visit the return tablet count was made to ascertain the compliance to the medication. 

The patients were instructed to contact the investigator at any time if they developed an 

exacerbation of any of the symptoms. Additionally at every follow-up visit i.e. Week 2, Week 4 

and Week 6 the patients were asked to participate in a questionnaire for adverse events. 

Evaluation procedures 

Efficucy parameters 

The disease activity was assessed at the screening visit, at Week 2, Week 4 and Week 6. The 

following symptoms were assessed. 

1. Joint Pain: Pain in the right knee, left knee, right hip, and left hip was graded separately by 

the patient as 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe Averaging the pain score of 

the affected joints arrived at the joint pain score. The maximum attainable score is 3 while 

the minimum attainable score is 0 

2. Joint Tenderness: Tenderness in the right knee, left knee, right hip, and left hip was graded 

separately by the investigator as 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe. Averaging 

the tenderness score of the affected joints arrived at the joint tenderness score. The 

maximum attainable score is 3 while the minimum attainable score is 0 

3. Joint Swelling: Swelling in the right knee, left knee, right hip, and left hip was graded 

separately by the investigator as 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe. Averaging 

the swelling score of the affected joints amved at the joint swelling score. The maximum 

attainable score is 3 while the minimum attainable score is 0 

4. Morning StiBess: Morning Stiffness in the right knee, left knee, right hip, and left hip was 

graded separately by the patient as 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe. 

Averaging the Morning Stiffness score of the affected joints arrived at the Morning 

Stiffness score. The maximum attainable score is 3 while the minimum attainable score is 0 

5. Functional Impairment: Functional Impairment in the affected joints was graded separately 

by the patient as 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe. Averaging the Functional 

Impairment score of the afiected joints amved at the Functional Impairment score. The 

maximum attainable score is 3 while the minimum attainable score is 0 

6. Modified KGMC lndex for Physical Fun~tion Criteria: The patients were asked to describe 

the difficulty in performing the below mentioned functions as 0 = Absent, 1 = Mild, 2 = 

Moderate, 3 = Severe and 4 = Prohibitive. 

i. Ascending stairs 

ii. Descending stairs 

iii. Rising from sitting 

iv. Standing 

v. Walking on floor 

vi. Going shopping 

vii. Rising from bed 


141

vliit fl-khv-y ddm9t4c diititis' 

&![I 'Bqh~W&'fdrdoiM 

x. 

xi?, 

Getting inlout from cycle/autorickshaw 

-+hCTh&l~ ~ b ~ ~ ~ & ~ i b h 

xii. Daily prayers 

diil ' raki#'a- dbtf? 

The ~odified''k&ht ihd& kdr~h'ysica~ Fdnction Ctiteria 'comprised the sum of the score for all 

the thirteen physical function criteria The maximum attainable Modified KGMC Index for 

Physical Function Criteria is 52 while the minimum attainable index is 0 

lnve&gators hsessment of Overall Efficacy: 

The 49veSt%?t9,1 K f PS~~$J$O ~ 9 9 4% % olyf?jtl& M~WY 9f! thet@rn@%:;ab th@,w-sPfmtsixt8 

d8e% 

rebeftclf3~rnPtQlW 

&%J~PR~,~W\~~RQR&@MW#W~~ 

3 = Far - when'there is minimal relief of symptoms 

= x~e~I~m~'sq0 $did@ SYSBIPtOls. 

5 = $,?~-c3?ar 5 !YM ~rctaa~4wormiagrbPsymptmg, 

= I~A~$~d~~Wlk@ I 

= &WP ~7 

Safety parameters 

TheL*dq&sesemti&to thes-&io~ ift!im$ w~s~~mdckk~~Wkzh~~ 

%p d%y'@&atH'JCheck 

list #,$he. Pnd ~flhesecad~Mh!arrri s&lrdesk W1Q ~ ~ w B ~ P & ~ T o w#&@8fi~''' I ~ 

I Heavy headlheadache 

ii :f&l&r&ctlrsisi~cmi 

iii Qiddihesst 

iv I@@ mtruth 

v wd.us& 

vi. irg'~iktdg 

vii IJ ~ ~ s f i 'iSd$€o?t n ~ ~ f 

viiP Eni)l?ha9 

ix E igastric burnihg 

x ~&S*W&G 

The adverse reactions were graded as 0 = None, 1 = MiId,.2 = Moderate and 3 = Severe 

Investigatomassessment ~f overall tolerability 

The investigator graded the overall tolerability to the inve~tigati*~&,~q;&epsog* the 

patient as: 

1 = Good - no side effects 

2 = Fair - mild to moderate side effects 

3 = Poor - severe side effects requiring withdrawal from therapy. 

SEL~T RESEARCH P # ~ ~ ~ ) E B C B X S E T J ' ~ Y ~ # ~ D I ~ ~ C ; 1-42 

I :

'&W#WBf3"aM Xctifify' 3S~ssment'vy,$i;bres $y th;cx~py~d 

~!@oi&i'% &w&~~~@s?r?he nbll hho 1 hells t ste 

significant difference within the group - - for change - from 

fourth and sixth week. 

t#~~kidk&ir,Ws'Wi& t k ~ at'g t ~ sigmcatdt! levdl W ~'OW 

Demographics and patient k f i ~ d ~ 

FiRy patients were enrolled in the study amongst which forty-six patients com@k%dW 

lKb#l fiW sga+sffahq~odY~~~~'ie~st&~tbinp~6ed~thsl~1~~\b 

#%t?.Yll ~*\l\~~TIibWi&gh 

duration of the disease was 3 1 46 * 39 59 months The nature of the complaint of the ehP&!XI 

~2%t~uf5sf4n@~~$s1~a%;ltiz3i~d~i&1rd ~ ~~16!@@j$&&t@hi~$b~&~~ 

~~~~0g?,fs~t,0)tingN3(m~ 

fiifXQ~Qbt8mtstbhiCiq-6ved tha pi&qnMih d l b i ~ b f l b ~ 0 ~ 

jflaT@b +~_cl$e ww W$@o efMs m.dmh~~~hi~btm&~mer,dt(Se% cdhg~rPliti&ws 

iL,Q2a24,1,,3, manths 

Clinical efficacy Results 

'The cllnlcal responses of the patients were determined and the r es~~&~(~\sW&in\TW\\w 

Joinf paln 

g$~fy," 

,&~~fi'fi{f 4% 6?qrcz&!4 2 ?& &9ftt trff4&% ~@#%@~ot%%kf?fi~teds~& 

A&~if&&&i$i&@&& 

'hb$lhne@lrg lhi ekiiiiiib NSfl~,;~~x~JL41~~j~~~~ 

pain of the affected joints at the ??-wee an 4 week e mean score for joint pain at 

the end of the second and fourth week were 0 96 i 0 4 and 0 66 & 0 28 resggs%&\,p 

:@n;lfi:antly less (p,< 0 05),tbw 265 0.42,th.e me@.bqeline si~orgf~r,iGndmm. R, ..:\ 

Cqmpurl~on of pre (NSAlDs supp~~pfin?,e

tenderness at the end of the second and fourth week were 0.69 * 0.3 and 0.46 0.3 1 respectively 

that were significantly less @ < 0.05) than 1.09 * 0.33, the mean baseline score for joint 

tenderness (Figure 2). 

Comparison of pre (NSAIDs supplemented with MI&) and post treatment (Sallaki after 

withdrawal of NSAIDs) values 

When therapy with NSAlD was withdrawn and only Sallaki administered for a period of two 

weeks from the fourth week of study period, no significant difference in the joint tenderness 

score at the sixth as compared to the fourth week was observed. However the mean score for 

joint tenderness at the end of the sixth week was 0.46 h 0.35 that was significantly less (p < 0.05) 

than 1.09 * 0.33, the mean baseline score for joint pain (Figure 2). 

Joint swelling 

Comparison of pre flSAIDs therapy) and psi treatment (NSAIDs supplemented with ,%llakr} 

values 

Supplementing the existing NSAID therapy with Sallaki resulted in a significant reduction in the 

swelling of the affected joints at the 2-w&k and 4-week endpoint. The mean score for joint 

swelling at the end of the second and fourth week were 0.54 * 0.28 and 0.33 * 0.29 respectively 

that were significantly less (p < 0.05) than 0.82 * 0.27, the mean baseline score for jbint swelling 

(Figure 3) 

Comparison of pre (IvSAIDs supplemented with SalU) and post treatment (Sallaki sfter 

withdrawal of NWDs) values 

When therapy with NSAID was withdrawn and only Sallaki administered for a period of two 

weeks fiom the fourth week of study period, no significant difference in the joint swelling score 

at the sixth as compared to the fourth week was observed. However the mean score for joint 

swelling at the end of the sixth week was 0.34 * 0.33 that was significantly less @ < 0.05) than 

0.82 * 0.27, the mean baseline score for joint swelling (Figure 3). 

Morning stiffn~s 

Comparison of pre (1VUIDs therapyl and post treatment (NLUIDs supplemented with SallakI) 

values 

Supplementing the existing NSAID therapy with Sallaki resulted in a yignificant reduction in 

mcrning' stiffness of the affected joints at the 2-week and 4-week endpoint. The mean score for 

morning stiffness at the end of the second and fourth week were 0.7 0.34 and 0.47 0.3 

respectively that were significantly less @ < 0.05) than 1.05 * 0.46, the mean baseline score for 

morning stiffness pigure 4). 

Comparison of pre (NSAIDs supplemented with Sallaki) and post treatment (Salk& after 

withdrawal of NWDs) values 

When therapy with NSAlD was withdrawn and only Sallaki administered for a period of ,two 

weeks &om the fourth week of study period, no significant diffwence in the morning stiffness 

score at the sixth as compared to the fourth week was observed. However the mean ocore.for 

morning stiffness at the end of the sixth week wab 0.45 * 0.37 that was significantly less @ < 

0.05) than 1.05 * 0.46, the mean baseline score for morning stiffness (Figure 4). 


-

Functional Impairment 

Comparison of pre (IvSAIDs therapy) and post treatment (NSAIDS supplemented with Sallaki) 

values 

Supplementing the existing NSAID therapy with Sallaki resulted in a significant reduction in 

hnctional impairment of the affected joints at the 2-week and 4-week endpoint. The mean score 

for functional impairment at the end of the second and fourth week were 0.88 * 0.4 and 0.58 * 

0.29 respectively that were significantly less (p < 0.05) than 1.14 * 0.4, the mean baseline score 

for fiinctional impairment (Figure 5). 

Comparison of pre (hrWfLls supplemented with ,%llaRi) and post treatment fsbllak~ afier 

withdrawul of NLWIDs) values 


weeks from the fourth week, of study period, no significant difference in the functional 

impairment score at the sixth as compared to the fourth week was observed. However the mean 

score for hnctional impairment at the end of the sixth week was 0.64 h 0.43 that was 

significantly less (p 0.05) than 1.14 0.4, the mean baseline score for functional impairment 

(Figure 5). 

Modified KGMC Index for Physical Functjon Criteria 

omp par is on of pre (N,c;AILls therapy) and post treatment (NUIDS supplemented wzth ,!!llub) 

values 

Supplementing the existing NSAlD therapy with Sallaki resulted in a significant reduction in the 

KGMC lndex for Physical Function Criteria at the 2-week and 4-week endpoint. The mean index 

at the end of the fourth week was 14.62 * 6.53 that was significantly less (p < 0.05) than 22.3 k 

5.86, the mean baseline index (Figure 6). 

Comparison of pre (N,SAIDs supplemented with Sallaki) and post treatment (.%llaki after 

withdrawal of NS4IUs) values 


weeks from the fourth week of study period, no significant difference in the KGMC lndex for 

Physical Function Criteria at the sixth as compared to the fourth week was observed. However 

the mean index at the end of the sixth week was 16 * 7.39 that was significantly less (p < 0.05) 

than 22.3 * 5.86, the mean baseline index (Figure 6). 

Overall efficacy 

The investigator reported the following responses as the overall efficacy of the treatment. An 

excellent response to the treatment in four patients, a good response in twenty-one patients, a fair 

response in sixteen patients, a poor response in four patients while a very poor response in just 

one patient. (Table 4) 

Overall tolerability 

All the forty-six patients who completed the trial reported a very good tolerability to the 

treatment. One patient reported of vomiting and epigastric burning of mild severity on the fourth 

week of study period but it discontinued gnrdually until the sixth week without necessitating any 

change in the medication. 


145

DISCUSSION 

fnstfr'liaqml Isnoifx~ar? 

~BP&a;Uiiitl"s"ii'c"duiB 'ih"'mosf'p&~le and is probably the most common joint dlsordefi,{fl,,@e 

(Z siug1;1) frrsrnlrsqrnr Isnoifantjt 161 

As the articular cartilage is aneural, the joint pain in OA must anse from other structures In 

t' n it ma b d 

o eop e; in .?&Q otters \1)%-4 it \?% may %J anse%om &\~A@R&W~C;~M~;Y(~I\~@BR 

microfractures m subchp~~~~ \~RI~% GY%~~WY 

,9&m?i#hfi 

BRF~ t J~&RRI%B~ 

4m~ep,fImqm~~ 

h e nsion ca 

vd&%?n, sd~%~3?&~fuX~~f$~B ~klp$rp*itLt 

&m~wd~s4fan~nf&$9f@t B i,!to72J0JRt ~9~f!f ?R&P%c!~.H?$sPT~~!R 

Pain-=. -- .- 

yd ptM& c T xi "ih 

tien" "04 ...-.. '. ..-, -- - 

n3m mPbnolf3q lobs 6A0!#i 9% bJii+d.%%t~ w~PMIR (k Bdyw$hP&$@@?~lc 

evlden'Ee o synovia in ammation may e as marked as that in the synovium of a p+twJ&h 

rheumatoid arthritis Synovitis in OA may be due to phagocytosis of shards of cartilaie and%one 

from the abraded joint surface 

$R:~B~?!~FP~~S+ \xJ,,\": ,&!%fitah. 

':mmuni compjexes, &htainIng 

?f&!$$b$# 

bsyFtjs ~ ~ f % ~ S&~WHF i & &I ~8 

i xs adf an i Jnernslqq 11% 

fajo ns c \ ~ - + br16 ,433+r-C 9ijJ t6 fi11911:1'3 n0133it~q I~?i~?(d1 161 ~3bfrI 3Mi)A 

tncreasing obility n 1 roving We patient's q u a l i t ~ 8 5 # ~ J ~ ~ T ~ ~ i fU i P ~ Qbe fP i . ~ ~ ~ 

~s~~$~9$ft9~ff?fie~k&~~~t!1~i~~~@ (mta~ad~tfh 

divided into non-drug therapy and pharmacological options The vigor of the therapeut~c 

terv i~ dic(gg~~~;$%~~e~Q,~?fiL~~~$~nQ~~~~&i?Ck\cjAv.~~~~q~,F~~&f3 

':a~y'8\bbhs'? reassuran e, instruction in joint p~otection, a * , ~ f i , ~ q < ~ l \ ~ y ~ y ~ 

QF T + dI Z6W ;k3w ~ JXIZ 

b rl;~iiirr< 16 db ~RC[J 

sdt'i~ bn3 ad1 ti3 xabni nssm 

'Yh2rip~)&9~b~ howev& is $liatrve, no p t ~ ~~~~9~~~ ~ grg.fegs, ~ m ~ y ~ 

the progression of, or reverse the pathologic c anges of OA in humans. Analgesics such as 

paracetamol and at times even a combination of paracetamol and codeine arf+&&gg~a 

. ~ w ~ re I ~ ~ ~ 3 ~ f 3~ 1 ? ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ h 

sfr14f94 e~intRfi&~fi~i~~9i~fide7t 

&fg'b;lyM$$f u e 1 SI ations 

1 cfisea~e 3 or w ere a a - a swt esic 3%~S~?$B 

trot nt 9znocJh IOBJ~~V 1%f& $W (1PbdP B % ~ @'B~~EoN~@Ms~~~z 

M 

ni 3znoqr.n 

(P sldsT) fnsi3~ sno 

Concern with respect to the appropriateness of NSAID administration in OA because o 7 their 

side effects, especially those related to the gastrointestinal tract is growing yfTbmmk.&@e

In a short-term study comparing an anti-inflammatory dose of ibuprofen (2.4 dday), an analgesic 

dose of ibuprofen (1.2 glday) and paracetamol (4 glday), no significant differences were found 

20 

between the treatments in terms of disability or pain on walking . In a study in which patients 

were repeatedly randomized to receive paracetamol or diclofenac, symptoms were adequately 

controlled by paracetamol alone in approximately 30 % of patients 21. Also in two recent 2-years 

comparative studies of NSAIDs (naproxen and sustained release diclofenac) in the treatment of 

osteoarthritis of the knee, significant number of patients previous1 controlled on NSAIDs were 

able to continue on paracetamol alone for the duration of the study x2-23 

Given that the symptomatic relief afforded by NSAIDs is no greater than that achieved by simple 

analgesics while the frequency and severitv of adverse effects are more with the former, NSAIDs 

are used only when analgesics and other hleasures have failed However NSAlDs when used, 

should be employed for short periods of tlme (L 1 to 2 months) and attempts continually made to 

withdraw treatment and reintroduce or mcrease the dosage of analgesic drugs 

Thus it may be concluded tFt, despite their being an inflammatory component in the 

pathogenesis of the disease, the magnitude of improvement afforded by NSAIDs is generally 

modest-as reported on an average, about 305'0 reduction in pain and 15 % improvement in 

€unction However the inflammation needs to be controlled as persistent inflammation ftllther 

results in cartilage degeneration and worsen~ng of the disease 

It may be suggested that the poor control of Inflammation is due to the inhibition of just one of 

the mediators of inflammation i e cyclooxygenase Simultaneous inhibition of lipooxygenase, 

the second major mediator of inflammation by the concomitant use of lipboxygenase inhibitors 

would probably result in a better control of inflammation. 

The present study was conducted with an attempt to prove the assumption Patients w~th 

osteoarthritis were prescribed Sallaki (400 mg) ti d for a period of four weeks in addition to 

their routinely prescribed NSAID After a period of four weeks their therapy with NSAlD was 

withdrawn and only Sallaki administered for an additional two weeks perlod 

A significant improvement in all the variables assessed was observed at both the Zweek and 4 

week end points The improvement in the signs and symptoms was sustained until the sixth week 

i e even aRer discontinuation of the NSAID therapy 

Supplementation of the existing NSAID therapy with Sallak~ resulted in a significant reduct~on 

in pain, tenderness, swelling, morning stiffness and fbnctional impairment of the affected joints 

the effect was observed both at the end of the second week and fourth week The modified 

KGMC index for physical function criteria also decreased at the end of the fourth week The 

KGMC index for physical function criteria is a powe&l instrument to study the health status of 

OA patients belonging to the Indian population It is a reliable and valid, multidimenaonal, 

quantitative tool to assess symptomatic benefits in Indian patients with OA knee 

Thus it cab be said that s~multaneous administration of Sallaki results in significant reduct~on In 

pain and disability while improving the mobility 


A synergistic effect of lipooxygenase inhibitors and cyclooxygenase inhibitors thus exists in 

controlling the inflammatory component of osteoarthritis. 

Furthermore, the improvement in the clinical signs and symptoms were maintained even after 

withdrawal of the NSAID therapy thereby suggesting Sallaki to be effective even when used as a 

sole therapy 

One may conclude from the present study that in OA patients once treatment with NSAID and 

Sallahi is initiated the need to continue with the NSAID is obviated It is preferable to continue 

w~th Sallaki on a long-term basis and gradually reduce the dose of NSAID or use it only 

intermittently i e during exacerbation of joint paln 


REFERENCES 

1. Chopra, A., Patil, J., et al. The BHIGWAN (India) COPCORD : Meth@ology adjrst 

infomation report. APLAR Journal of Rheumatology 1997; l(1): 145-54. 

2. Das, S.K., Ramakrishnan, S. Osteoarthritis: Diagnosis and management. JIRA 1999; 7(4). 

139-145. 

3. Dequeker, J., Hawkey, C., Kahan, A., .et al. Improvement in gastrointestinal tolerability of 

the selective cyclooxygenase (COX)-2 inhibitor, meloxicm, compared with piroxicam: 

Resutts of the safety nd eficacy large scale evaluution of COX-inhibiting therapies 

(SELECT) trial in osteourthritis. Br. J. Rheumatol 1998; 37: 946-5 1 

4. Hawkey, C., Kahan, A,, et al. Gas@ointestinal tolerability of meloxicam compared to 

dzcofenac zn osteoarthritis patients. The International MELISSA Study Group. Br. J. 

Rheumatol 1998; 37: 937-45. 

5. Brandt, K.D. Osteoarthritis: In Fauci AS, Braunwld E, et a1 (Eds): Harrison's Principles of 

Internal medicine 1 4 ed., ~ Mc Graw-Hill. In~rnational Edition 1998: Vol. 2: pp. 1935-41. 

6. Ford-Hutchinson, A. W., et al (1980) Nature. 286,264. 

7. Malmsten, C. L., et al. (1980) Acta Physiol. Scand. 110,449. 

8. Bray, M.A., et al. (1981) Br. J. Pharmacology.. 72, 483. 

9. Wedmore, C.V., et al. (1981) Nature. 289,646. 

10. Hagers Handbuch der pharmazeut. Praxis (1972) 4& Ed., Vol. 111 pp. 491, Spinger-Verlog, 

Berlin, Heidelberg New York. 

1 1. Ammon, H. P. T., et al. (1991) Planta Medica. 57,203 - 207. 

12.. Singh, G. B., et al. (1 9sb) Agents and Actions. 18, 3 / 4, 407-4 12. 

13. Menon, M. K., Kar, A. (1971) Planta Medica. 19, 333 - 341. 

14. Atal, C. K., et al. (1980) Ind. J. Parn1.,12, 59. 

15. Atal, C. K., et al. (1981) Br. J. Pharm., 74, 203. 

16. Atal, C. K., et al. (1982) XV IPS (Abstract), Chandigarh. 

17. Chandrashekaran A.N., et al. (1995) JIRA, Eflect of ,Sirllaki in the treatmen1 c?f Kheumcrtoid 

arthritis. Vol. 3 -No. 3, 101-106. 

18. Rajagopal, S., et al. (1995) ,JIM, Assessment of the therupeutic ~fll?ct qf Sallczki (Boswelliu 

serrata) in the treatment of juvenile rheumatoid arthritis. Vol. 3 - No. 3, 107- 1 10. 

19; Lohokare, S. K. (1 995) JIM, A (,'linical Trzal of Ro~wellia Serrata &ScdZuki) in the trecztment 

of Osteoarthritis. Vol. 3 - No. 3, 1 13- 1 16. 

20. Bradley, J. D., Brandt, K. D., et al. (,'omparison of an anti-zn$ummatoory &,ye of ib.~dprc?fen, an 

analgesic dose of ibuprofen and acetaminophen in the treatment 4 patienls with 

osteo&rthritzs of the knee. N.E.J.M. 199 1 ; 325-87 

21. March, L.M., Irwig, L.M., et al. N-of-] trials comparing u non-steroidal antilinflummutory 

drug andpacetamol on osteoarthritis. B.M. J. 1994,309: 104 1. 

22. Williams, H.J., Ward, J.R., et al. (.:omparison of naproxen mui acetaminophen in cr two-year 

study of treatment of osteoarthritis of the knee. Arthritis and rheumatism 1993; 36: 1 196 

23. Dieppe, P., Cushnagan; J., et .al. A two-yeur placebo controlled trial of non-steroihl untiin$ammatory 

therapy in osteoarthritis of the knee joint. Br. J. Rheumatology 1993; 32-595. 

- - 


Table I. Nature of cornpla~nt 

- ..... 

.-,--p--.-.- .-.-- -- 

Complaint - . 

Pain in knee joints - 

Pain in hip joints I I 

Stiffness in knee joints 42 

Stiffness in hip joints 14 

~ii'ficult~ in walking and/ or climbing 19 . . - 


Table 2. Details of the medication 

Medication Dose No of patients on the medication 

T. nimesulide lOOmg b.i.d 18 

T.meloxicam 15mgb.i.d 19 

T. dolonex 20mgo.d 2 

C.indomethacin 75 mg o.d 1 

C. indocid 25 mg t.i.d 3 

T. ibuprofen 400 mg t.i.d 1 

T. dicloram 100mgod I 

The medication described is the one on which the patients had been stabilized for the past one- 

month. 

- - 


151

Table 3. Efficacy results with Sallaki (400 mg) t.i.d. in osteoarthritis 

Clinical Parameters 

Joint pain 

Baseline 

1.26+ 0.42 

-- - 

Mean Score on 

Week 2 Week 4 

0.96 * 0.4 * 0.66 * 0.28 * 

- 

Week 6 . 

0.73 * 0.39 * 

Joint tenderness 109+033 069h033 * 046*031 * 046*035 * 

Joint swelling 082*027 054i028* 033*029* 034+033* 

Morning stif'fness 105*046 07h034* 047&03* '045*037* 

Functional impairment 114+04 088%04* 058*029* 064*043* 

Modified KGMC lndex for 22 3 + 5 86 -- 146*653* 16+739* 

Physical function criteria 

* : significantly different from baseline values atxp ( 0.05) 

Values are expressed as the mean * std. deviation of 46 observations 


Table 4. Overall efficacy of the treatment 

Response No. reported by Investigator 

Excellent 4 

Good 2 1 

Fair 16 

Poor 4 

Very poor 1 

Values given are the number of responses reported by the investigator for the 46 enrolled 

subjects. 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS 1 53

Figure 1: Ef'fect of treatment with Sallaki (400 mg) t.i.d. on the Joint Pain Score of patients with 

Osteoarthritis 

"significantly different from Basel~ne score at (11 .- 0 05) 

L'ali~es are expressed as the Mean + Std Deviation of 46 observations 


Figure 2: Effect oftreatment with Sallaki (400 mg) t.i.d. on the. Joint Tenderness Score of 

patients with Osteoarthritis 

- - - - .- - - - .-. --- . -. - - . . . -~ ---- ~- - .. - - 

* significantly different from Baseline score at (p -: 0 05) 

Values are expressed as the Mean + Std Deviation of 46 observations 

- - ~ 

~ 

~ ~ 


T'"

Figure 3: Effect of treatment with Sallaki (400 mg) t:i.d. on the Joint Swelling Score of 


* : significantly-different from Baseline score at (p < 0.05) 

Values are expressed as the Mean It Std. Deviation of 46 observations 


Figure 4: Effect of treatment with Sallaki (400 mg) t.i.d. on the Morning Stiffness Score of 


* . significantly different from Baseline score at (p < 0.05) 

Values are expressed as the Mean + Std. Deviation of 46 observations 


157

Figure 5: Effect of treatment with Sallaki (400 mg) t.i.d. on the Functional Impairment Score of 


* . significantly different from Baseline score at (p 0 05) 

Values are expressed as the Mean + Std Deviation of 46 observations 


Figure 6: Effect of treatment with Sallaki (400 mg) t.i.d. on the Modified KGMC Index for 

PhysicalFunction Criteria of patients with Osteoarthritis 

* : significantly different from Baseline score at (p < 0.05) 

Values are expressed as the Mean * Std. Deviation of 46 observations 


DOUBLEBLIND RANDOMIZED CONTROLLED TRIAL OF SALLAKI (600 MG) 

VS DICLOFENAC (50 MG) IN THE TREATMENT OF RHEUMATOID ARTHRITIS 

* Bichile, L S , Rajadhyaksha, A , Kini, S 

* Author for correspondence 

' Dr.L.S.Bichile M.D. 

Professor & Head Department of Medicine It Chief Rheumatolgy 

K.E M. hospital, Parel, Mumba~ - 400 0 12 

Dr A Rajadhyaksha M D 

Assoc Prof 111 Medlcine 

K E M hospital, Parel, Mumbai - 400 0 12 

Dr. S. Kini M.D 

Lecturer in Medicine 

K.E.M. hospital, Parel, Mulnbai - 400 0 12 


ABSTRACT 

In an open study, fifty patients with primary osteoarthritis of the knee andlor hip were treated 

with Sallaki8 (400-mg t.i.d) along with the NSAID, which they had been routinely consuming 

for their disease The duration of the treatment period was four weeks. At the end of the forth 

week treatment with NSAID was withdrawn and only Sallaki8 (400-mg t.i.d) administered for 

an additional two week period. The following variables were tested: Joint pain, Joint tenderness, 

Joint swelling, Morning Stiffness and Functional Impairment for the hip and knee joints. The 

patients also participated in a questionnaire that included all the thirteen physical hnction 

criteria of the KGMC Index. A statistically significant improvement in all 'the variables were 

observed at the Week 2, Week 4 and Week 6 end points. The improvement was thus sustained 

even after withdrawal of the NSAID therapy. The drug was also well tolerated with no reported 

incidence of adverse drug reaction 

Key words:, Sallaki 8, NSAID, Osteoarthritis 


161

INTRODUCTION 

Recognition of rheumatoid arthritis as a "medical emergency" led to a change in the 

therapeutic strategy fiom " go-slow-and-go-low" to "aggressive early treatment" aimed both 

at symptomatic relief (controlling synovial inflammation) prevention of joint destruction and 

loss of fknction (modification of the progressive course of the disease). 

Reasons for the increasing popularity of the aggressive approach were the uncommon natural 

remissions and the substantial morbidity, work disability, and mortality rates observed in the 

patients 

Long term treatment with DC-ARTs/DMARDS is therefore instituted early in the course of 

the disease before the occurrence of irreversible joint damage. However the use of DC- 

ARTsIDMARDS as well as of NSAIDS are associated with a wide spectrum of side effects ' 

A recent study on the pattern of adverse drug reaction with NSAIDS, DC-ARTs/DMARDS 

and steroids on Indian population revealed that gastrointestinal disturbances is the most 

frequent adverse event and observed in 54 1% of patients Cardiovascular 1 respiratory 

system abnormalities were observed in about 3 1 88 % of the patients, cutaneous reactions in 

20 8% and nervous system related symptoms in I2 1% of the patients 2 

Thus the search for agents with anti-inflammatory and disease modifying potential whose 

long-term use would not be associated with side effects still continues. 

The gum resin exudate of Boswellia serrata that has been advocated in the treatment of 

'rheumatism in Sushrutha Samhita and Charak Samhita is known to possess remarkable anti- 

3 

inflammatory and anti-arthritic effect and to be devoid Of toxicity on prolonged use . 

Pharmacological studies conducted on the extract of Boswellia serrata to delineate its mode 

of action revealed the extract to be acting by a mechanism similar to non-steroidal group of 

antikthritic drugs with the added advantage of it being free fiom side effects and gastric 

4 

irritation and ulcerogenic activity 

The extract can inhibit the prodbction of leukothene-type mediators of inflammation at low 

concentrations and prostaglandin-type mediators of inflammation (the PGF series) at higher 

5 

concentrations without impairing the PLAz action 

The extract can also inhibit the expression of 24 hour delayed type hypersensitivity reaction 

(cell mefliated immunity) and primary humoral response to SRBC in mice (humoral 

6 

immunity) 

Marked analgesic effects of rapid onset i.e 30 minutes which lasts for about 2 hours has been 

7 

obsewed with the non-phenolic extract of Boswell~a serrata 

These findings suggests that the gum resin exudate of Boswellia 'serrata can play a role in 

controlling the signs and symptoms of RA by virtue of its anti-inflammatory and analgesic 

effect and can also prevent the progression of the disease by inhibiting the cell mediated and 

humoral responses 


Recent evidence suggests propagation of RA to be an immunologically mediated event with 

the inflammatory process in the tissue driven by the CD4+ T cells infiltrating the synoviunl. 

If the extract is able to control the persistent tissue inflammation (i e persistent T cell 

activity) that is reminiscent of delayed type hypersensitivity reaction occurring in response to 

soluble antigens or microorganisms, it may help in preventing the progression ofthe disease 

However before one can claim the superiority of Bo.swell~u .serrutu over conventional drugs 

on account of the absolute freedom from side effects it is imperative to evaluate ~ts antiinflammatory 

and disease modifying potentials in RA patients 

The crude extract of Ho.vwellru serrutcr resin is available 111 the Intf~an market under the trade 

name "Sallaki" from Gufic Health Care Ltd Well-controlled clinical trials \~th Sallaki ha\ e 

been conducted in the past on patients with rheumatoid arthritis and osteoarthrltis 

Sallaki (400 mg t.i.d) when administered along with anti-inflammatory drugs like aspirin, 

indomethacin and ibuprofen for a period of six months in patients with rheumatoid arthritis. 

produced a statistically significant improvement with respect to pain score, number of joints. 

articular index, swelling score, PIP circumference, grip strength, ESK and CKP. A significant 

reduction in the rheumatoid factor was observed wh~ch seemed to suggest ~ts probable 

disease modifying potential ' 

When Sallah~ (400-mg t I d) was assessed for ~ts therapeut~c effect in ju~en~le ~heumdto~d 

arthr~tls it demonstrated a potentla1 In produc~tig a remlsslon In the clln~ciil s~gn$ 'ind 

symptoms Besides histologically ~t shoned to produce healing In the svnm [urn bv Inciedsi~le 

fibrosis aFter sixth month of therapy 9 

Sallaki (200-mg t i d) when used in the treatment of osteoarthritls showed encouraging results 

in early cases having mild pain with no radiological changes In the jcrlnts In the patlents ~clth 

long-standing disease with moderate to severe radiological changes ~t shomed a fair to pool 

response 10 

Results of the three clinical trials with Sallaki seemed to suggest its efXcacy In relleving the 

signs and symptoms of rheumatoid arthritis and osteoarthi-itis w~thout producrng any side 

eff'ect eken on long-term use 

The results of the previous trials encouraged us to conduct a study where~n the eflficac? of 

Sallahl would be compared with the routinely prescribed anti-inf1amnl:ttor-y agents in 

reliev~ng the signs and symptoms of rheumatoid arthritis 

Thus the objective of the present study was to compare the ef'ficacy and tolerance of Sallahr 

(600 mg t.i.d) with Diclofenac sodium (50 mg t i.d) in providing symptomatic rel~ef to 

patients with rheumatoid arthritis The trial was conducted as a double bllnd randomized 

parallel group study 


163

MATERIAL AND IMETHODS 

Patients selection 

Consecutive patients with active classical or definite rheumatoid arthiitis, according to the 

American Rheumatism Association (A.R.A.) criteria, attendin8 the Rheurnatology O.P.D. at 

K EM Hospital were enrolled into the study The patients were includcdif they had 

atleast four of the seven diagnostic criteria established by the A.R.A. and if their disease state 

was characterized by the presence of atleast two of the following: 

1 duration of morning stiffness of at least 34 hour or more 

2 atleast six painful or tender joints on motion 

3 three inflamed joints 

4 erythrocyte sedimentation rate greater that 30 mrnhr as determined by the Westergreen 

method 

Patients having developed rheumatoid arthritis before 16 years of age, or thdse with severe 

disabling arthritis rendering them eligible for surgical intervention or those incapacitated or 

bedridden were not included in the trial. 

Patients with ongoing therapy with anticoagulant, hydantoin, dorticosteroids, methotrexate,. 

gold, penicillamine or lithium or having undergone a thaapy with the same in the previous 

three months were also not included in the trial 

Pregnant, lactating women or women at a risk of becoming pregnant were not included. 

Patients with a history of active peptic ulcer in the preceding six months or bleeding ulcers at 

any time in the past, or those exhibiting hypersensitivity and / or intolerance to NSAID's 

including a history of aspirin induced bronchospasm were excluded from the trial. 

Patients having received any investigational drug in the preceding one-month _or having 

donated blood in the past three months were also excluded from the trial. Patients with severe 

renal, hepatic, hemopoetic disease or severe cardiac insufficiency as revealed by laboratory 

investigations or other tests were also excluded from the trial 

Previous anti-inflammatory treatment were discontinued for atieast five days prior to 

initiating the therapy with the investigational drugs and only analgesic therapy with 

paracetamol was allowed to control symptoms of pain during the wash out period 

Consumption of other analgesics except paracetamol, antipyretics, tranquilizers, hypnotic, 

andlor anti-inflammatory drugs were prohibited during the trial to avoid any interference in 

evaluating the investigational drug treatment 

The protocol had been reviewed and ratified by the Ethics committee at K.E.M. Hospital. All 

the patients gave written informed consent before enrollment into the trial. 

Study Design 

The study was conducted as a double blind, randomized, paraliel group comparative trial. 

After the patient satisfied the entry requirements, a complete medical history was taken and a 

general examination performed The disease activity was measured by counting the number 

of tender and swollen joints, determining the digital joint circumference, grip strength, 

duration of morning stiffness, time required to walk 50 feet and VAS score The painhl and 


swollen joints were scored using a scale of 0, 1, 2 or 3 to evaluate the severity of the 

inflammatory condition of each joint. 

The disease activity measurements were conducted during the screening visit, at baseline i e 

prior to initiating the investigational drug therapy (Week 0), at the end of the first week, 

second week and thereafter at the fourth week i e the end of the study. 

Laboratory investigation like ESR, CRP, Rheumatoid factor, blood chemistry, hematological 

and urine routine were performed at baseline and then repeated at the end of the study i e 

Week 4 

At the end of the study the investigator assessed the overall efficacy and tolerability to the 

treatment. 

The dose of Sallaki was (600 mg. ti d) and of Diclofenac sodium (50 mg t I d) divlded 

morning, afternoon and night The rescue medication paracetamol and the invest~gatlonal 

drug were provided to the patients at every follaw - up visit 

At every visit the return tablet count was made to ascertain the compliance to the medication 

and the paracetamol consumption. 

The patients were instructed to contact the investigator at any time if they developed an 

exacerbation of any of the symptoms 

Evaluation Procedures 

liflicczcy /xzrrzmeter.s 

The disease activity was assessed at the screening visit, at baseline i.e. Week 0. at Week I. 

Week 2 and Week 4. The following symptoms were assessed: 

1. VAS score: Patients assessment of pain severity during ,day and night was evaluated 

.using the VAS score. The patient was asked to place a mark on a 10-cm long standarti 

scale assuming that 0-cm indicated no pain and 10-cm indicated maximum pain. The 

distance of the point marked from O cm was calculated and recorded in Iiiln. 

2. Duration of morning stiffness recorded in minutes 

3. Time to walk 50 feet recordid in minutes. 

4. Grip strength in mm Hg: The cuff of a mercury sphygmomanometer was inflated to 20 

mm Hg after which the patient was asked to squeeze the cuff to the best of hislher 

ability and the rise in the level of the mercury was recorded. The mean rise in mm Hg 

calculated for three tries by each hand was taken as the grip strength) 

5. Number of swollen joints: The presence or absence of swelling in the following joints 

were determined; Temporomandibular ( TM ) Sternoclavicular (SCL), 

Acromioclavicular (ACL), shoulder, elbow, wrist, Digital interphalangeal (DIP) (2-S), 

Interphalangeal (IP), Proximal.interphalangeal (PIP) (2-5), Metacarpophalangeal (MCP) 

(1-S), hip, knee, ankle mortis, ankle tarsus, Metatarsocuneiform (MTC), Sacroiliac (SI) , 

Interphalangeal LP (feet), Proximal interphalangeal PIP (2-5) and Metatrsophalangeal 

(MTP) (1 -5). 

6. Swelling score: Swelling in the affected joints was graded as 0 = Absent, 1 = Mild, 2 = 

Moderate, 3 = Severe and a composite swelling score was arrived at by averaging the 

swelling score of the affected joints. 


165

7. Number of tender joints : The presence or absence of tenderness in the above mentioned 

jo~nts were determined 

8. Tenderness score Tenderness of the affected joint on palpitation was graded as O= No 

pain, I= Paln. 2- Pam and wincing, 3= Pain, wincing and withdrawal, 4= Patient d ~d not 

allow palpitation and the composite tenderness score was arrived at by averaging the 

tenderness score ofthe affected joints. 

9 Digital joint circumference. The swelling in the digital joints was evaluated using 

specially des~gned jeweler's rings (diameter ranging from 10-33 mm). 

'She fiillaw~ng porctmeters were also evaluated to determine the efticacy 

I ii'aracetamcil ccmsurnptlon throughout the trial per~od I e fou~ ueeks 

2 Er~throcyte sed~mentat~on rate (Westergreen method stated In ninilhr) at basel~ne and 

Weel-. 4 

7 Wlleui~l~~to~d fact01 at baselme and Week 4 

-I (' Keact~ce pruteln at basel~ne and Week 4 

10 Pn~est~gittor s oplnlon on efficacy at the coniplet~on of the tr~al graded as fidlo~s Ciooti 

s~ginticant ~mprc)\ernent, Fair = moderate ~niprovemciit and Poor = no Irnpln~ement 

1,abolator~ ~ncest~gatlons 'B'lie following lnvestlgat~ons were conducted at bascl~nc and 

~epmtcd at the tcrm~nat~on ofthe tr~al I e Week 4 

Wed blood cell count Hernoplob~n. Complete and d~fferent~al cvh~te blood cell count t '~lilt 

:inalks~s Blood sugal (fkst~ng) Blocrd LII~CI nltrtrper~ Serum creat~nrne 5erurii b~llrub~n, 

Zs( I' E. I c~t,il p1citrllis Album~n and c;lobulin 

Ln~est~patc~i\ ,IL .~\\i~~crll of o\tl,il! tr>le~~rl)~llt\ 

rlit ~ncestig~tto~ ~i~~lecl t11t (,\~l~ty to the ~ncest~gat~or~al drug on lnterrogiitlng the 

patient as t luod 110 SI~C. efle~ts. bn~r ~n~ld to {nodel-ate slde ctrects, IJoor = seLcrc \1(1c 

effect\ i r,qrili III: \h, ~tlid~d\c~tl ti0111 thernln 

, 

I ' 

Ill ii~~t.!st .~crr 11, ,i:~- IILC,~~~ v;i~r,ibles hhpther measured or calculated were subjected to 'I 

~.NI~Y! ,,I I~II[>.~IIQ.~ I IL ,: 9 hc n~rll hypothes~s tested has that there was ,no stat~stic~ill\ 

srzn~fi~~iiil ~l~l'fcrcncc CIIII~,I~G t~lt'ttment groups and wlth~n treatment groups for basel~ne 

asseb>rnclliS, .end ch,tnge frc,m bi~\eline assessment calues at the fourth week 

~)l,~niie~i (;,ill \$[be ~oiiip;+~ 15on \%a\ inidde for B)lclofenac sudiuni velsus Sallak~ and also ~ ~ t h ~ n 

c'tel~ lICcjt,l~cnt groups .A11 cc>nlpar1sons were tested at a s~gn~ficance level of p - 0 05 

In tr~ticr t:i suinmar~ze thc -I beech tredtnient results, only the mean assessment ti>r bascline 

'~nd the nie'ln assessment at the end cif the treatment perrod (4 weeks) are presented as Weel 

(1 . t L g i !i #-ti. 4 iespecti\el\. 

5U/< ' 

Ilc i ih(.~,rtoi~ tesls were anal\:ed tor treatment effects to e~aluate safety uslng palred t test 

Ill t,tllr-; \!ere cons~dered srpn~fic;inf at (p 0 05) 

SELECT RESEARCH PAPEha ON EVIDENCE BASED AYURVEDIC DRUGS 166

OBSERVATIONS 

Demographics and Patient characteristics 

Forty-seven patients were enrolled in the study amongst which thirty-thl-ee patients 

completed the trial (18 on the diclofenac sodium group and 15 on the Sallaki group) The 

mean age of the patients in the diclofenac sodium group is 37.67 * 13.5 whi!e the mean age 

of the patients in the Sallaki group is 43.47 i 13.27. Twenty-six amongst the thil-ty-ttlree 

patients who completed the trial were females while the remaining six patients were males. 

The mean duration of the disease in the Sallaki group was 3.09 i- 2.77 years while that I ~ I 

diclofenac sodium group was 2 * 3.9 years and were not significantly difrerent from each 

other 

Clinical Efficacy Results 

The clinical responses of the patients were determined and the results are as shown In 1 able 

1.28~3 

VAS score 

('otiip~zri.~~t~ ofpre and post /rt?utrnen/ vcr1iic.s 

Both Sallaki and Diclofenac sodium produced very significant improvement in the pat~enl's 

perception of pain at the 4-week endpoint when compared to baseline. The mean V.4S score 

for the Sallaki group at Week 4 is 48.57 * 27.49 that is significantly less (p .: 0.05) than the 

mean VAS score at baseline of 64 14 + 28.03. Similarly the mean VAS score for the 

Diclofenac sod~urn group at Week 4 is 44.06 + 25 which is also .sigtiiticantly less (p . 0 05) 

tllan the mean b~seline VAS s.:ore of 57 71 * 23.7 

l )i/Ii,~.c~ti~.e h~~tw~~cn Sclllczki and I )IcIO~~~~LIC .sodil~tn 

There was no significant difference between Sallaki and Diclofenac sodium in reduc~ng thc 

patient's perception of pain. The mean baseline VAS scores for Sallaki and ~iclofenac \\el-e 

not significantly different from each other Besides the mean absolute difference between tllc , 

pre-treatment and Week 4 VAS score for the Sallaki and Diclofenac sodium group that were 

24 63 k 22.9 and 21.42 * 22.06 respectively were also not significantly different from each 

other. 

Grip strength 

('otn/~cwi.son ofpre czrzdfio.st lrelzfrnent vu1ue.v 

Both Sallaki and Diclofenac sodium produced non-significant improvement in the grip 

strength at the 4-week endpoint when compared to baseline The mean grlp strength in the 

Sallaki group at Week 4 is 82.07 i- 58.15 that is not significantly higher than the rnenn 

baseline grip strength of 75.14 * 37.4. Similarly the mean grip strength for the D~clotenac 

sodium group at Week 4 is 90.74 i 42.9 which is not significantly higher than the rneiiil 

baseline grip strength of 82.58 * 44.7. 

ll~fferenct! hetweet? Scrllc~ki utzd I)ick!fencrc .sodirrrn 

There was no significant difference between Sallaki and Diclofenac sodium in increasing thc 

grip strength at Week 4. The mean baseline grip strength score for Sallaki and L)rcloltnac 

were not significantly different from each other. Bes~des the mean absolute difference 

between the pre-treatment and Week 4 grip strength score for the Sallaki and D~clotnac 


the 

167

sodium group that were 39.73 + 37 9 and 23.24 + 18 3 respectively were also not 

significantly different from each other 

Duration of morning stiffness 

('ompczrzscm ofpre undpost trecztment values 

Both Sallaki and Diclofenac sodium produced non-significant decrease in the duration of 

morning stiffness at the 4-week endpoint when compared to baseline The mean duration of 

morning stiffness for the Sallaki group at Week 4 is 61 93 + 76 46 which is not significantly 

less than the mean duration of morning stiffness at baseline of 68 36 + 63 2 Similarly the 

mean duration of morning stiffness for the Dlclofenac sodium group at Week 4 is 51 33 + 

59 2 which is not significantly less (p 0 05) than the mean duration of morning stlffness at 

baseline of 80 88 + 5 l 8 

Ihference between Strlluk~ und I)rciqfenuc sodzutn 

There was no significant dlt'ference between Sallaki and Diclofenac sod~um In decreasing the 

duration of morning stiffness at Week 4 The mean baseline readings for duration of morning 

stiffness for Sallaki and Diclofenac were not significantly different from each other Besides 

the mean absolute difference between the pre-treatment and Week 4 readlnps for duration of 

morning stlffness for the Sallaki and Dlclofenac sodium group that were 38 53 + 40 29 and 

44 84 + 42 7 respectively were also not significantly different from each other 

Time to walk 50 feet 

('ompczrison of pre tndpost treuttnent values 

Both Sallaki and Diclofenac sodium produced non-significant decrease in the time required to 

walk 50 feet at the 4-week endpoint when compared to baseline. The mean time required to 

walk 50 feet for the Sallaki group at Week 4 is 33.80 5 16.4 which is not significantly less 

than the mean time required to walk 50 feet at baseline of 35.4 + 19.2. Similarly the mean 

time required to walk 50 feet for the Diclofenac sodium group at Week 4 is 36.37 + 14.5 

wh~ch IS not significantly less than the mean time required to walk 50 feet at baseline of 

43.26i 188 

1 )l fferencc~ helween Sullukl rznd Dlclofinac sodium , 

There was no s~gniticant d~fference betwcen Sallakl and Dlclofenac sodlum In decreasing the 

time requ~red to walk 50 feet at Week 4 The mean baseline value for the time required to 

walk 50 feet for Sallak~ and D~clofenac were not s~gnlficantly d~fferent from each other 

Besides the mean absolute difference between the pre-treatment and Week 4 value for the 

tlme requ~red to walh 50 feet for the Sallak~ and Dlclofenac sodium group were 11 98 + 12 3 

and 12 47 * 11 05 respectively and were not s~gnificantly d~fferent from each other 

Digital joint circumference 

('om/~urzson q'pre undpost treuttnent vu/ues 

Both Sallaki and Diclofenac sodium produced non-significant decrease in the digital joint 

circumference at the 4-week endpoint when compared to baseline The mean digital joint 

circumference for the Sallaki group at Week 4 is 22 8 + 6 4 which is not significantly less (p 

< 0 05) than the mean digital joint circumference at baseline of 23 2 + 2 86 Similarly the 

mean digital joint circumference for the Diclofenac sodium group at Week 4 is 23 1 1 h 2.88 


which is not significantly different (p < 0 05) from the mean digital joint circumference at 

baseline of 23.16 + 2.5. 

lhfference between Salluk~ and Dzclofenac sodzum 

There was no significant difference between Sallaki and Diclofenac sodium in decreasing the 

digital joint circumference at Week 4 The mean baseline value for digital jo~ut c~rcutiiference 

for Sallaki and Diclofenac were not significantly different from each other Besides the mean 

absolute difference between the pre-treatment and Week 4 value for dlg~ial joint 

circumference for the Sallaki and Diclofenac sodium group were 2 41 + 5 58 and 0 83 i O 87 

r~spectively and were not significantly different from each other 

Number of swollen joints 

('ompcrrison of pre ~zndpost treatment i~alues 

Diclofenac sodium but not Sallaki produced a significant-decrease in the number of swollen 

joints at the 4-week endpoint when compared fo baseline. The mean score for number of 

swollen joints for the Sallaki group at Week 4 is 9.5 + 10.1 which is not significantly less 

than the mean score for number of swollen joints at baseline of 11.42 7.43. 'T'he mean'score 

for number of swollen joints for the Diclofenac sodium group at Week 4 is 4:63 + 3.88 which 

is significantly less (p < 0.05) than the mean score for number of swollen joints at baseline ot' 

8.44 + 5.9. 

1)~firence between SaZlakr and D~cb !ferric sodium 

There was no significant difference between Sallakr and Diclofenac sodium In decreasing the 

number of swollen joints at Week 4 The mean baseline value for the number of s\\ollen 

jo~nts for Sallaki was 15 21 which is significantly higher than (p 0 05) 7 58. tlic hnseltne 

value for the number of swollen joints for the D~clofenac group However the mean absolute 

difference between the pre-treatment and Week 4 value for the number of swollen joints fo~ 

the Sallaki and Diclofenac sodium group were 7 59 + 6 I0 and 4 71 5 4 36 respect~\elv and 

were not significantly different from each other 

Number of tender joints 

Composite swelling score 

('c)m/)~:rlsor~ c?fpre and post treatment va1zre.s 

Diclofenac sodium but not Sallaki produced a significant decrease in the composite swelling 

score at the 4-week endpoint when compared to baseline The mean composite swelling score 

for the Sallaki group at Week 4 is 11 33 k 11 25 which is not significantly less thhn the mean 

composite swelling score at baseline of 15 33 11 The mean composite swelling score for 

the Diclofenac sodium group at Week 4 is 5 56 * 4 28 which is significantly less (p 4 0 05) 

than the mean composite swelling score at baseline of 9 00 + 5 8 

/)/fferetlce between A %z//~ arzd 1)rclofenuc sodlum 

There was no significant difference between Sallaki and Diclofenac sodium in decreasing the 

composite swelling score at Week 4 The mean baseline composite swelling score for Sallaki 

and Diclofenac sod~um were not significantly different from each other Besides the mean 

absolute difference between the pre-treatment and Week 4 composite swelling score for the 

Sallaki and Diclofenac sodium group were 9,25 + 8 9 and 4 71 * 3 92 respectively and were 

not significantly different from each other 

Composite tenderness score 

( 'omp~~rison of /)re atzdpos[ treatment vultres 

Sallaki but not Diclofenac sodium produced a significant decrease in the composite 

tenderness score at the 4-week endpoint when compared to baseline. The mean Week 4 

composite tenderness score for the Sallaki group is 17.71 5 16.6 that is significantly less (p < 

0.05) than the mean baseline composite tenderness score of 30.00 + 20.3. Hbwever the mean 

composite tenderness score for the Diclofenac sodium group at Week 4 is 15.16 * 14.5 which 

is not significantly less (p

Paracetamol consumption 

The mean paracetamol consumption throughout the study period (4 weeks) in the Diclofenac 

sodium group is 49:52 * 25.7 which is not significantly different from the mean paracetamol 

consumption in the Sallaki group of 53.28 * 18.9. 

Overall efficacy 

The overall efficacy of the treatment amongst the 15 patient who completed the trial with 

Sallaki and 18 patient who completed the trial with Diclofenac sodium is as shown in Table 

6. 

Safety 

Comparison of pre and post treatment laboratory values 

No abnormalities in the laboratory tests were observed for both the treatment groups (Table 

4, 5). No statistically significant change in the pre and post values for hemoglobin, white 

blood cell count, fasting blood sugar,-blood urea nitrogen, serum creatinine, serum bilirubin, 

SGPT, serum proteins albumin and globulin was observed for both the groups. 

Comparison of the overall tolerability 

The overall tolerability to the treatment amongst the 15 patient who completed the trial with 

Sallaki and amongst the 18 patient who completed the trial with Diclofenac sodium is as 

shown in Table 6. 

Patients complaint 

One patient in the diclofenac sodium group complained of abdominal discomfort for 15 days 

that was of moderate severity requiring discontinuation of the therapy. Two patients 

'complained of GI side effects amongst which one suffereft from dyspepsia for 7 days. One of 

the patients on therapy with diclofenac sodium complained of piles without bleeding during 

the last 10 days of treatment. One patient in the Sallaki group complained of dyspepsia of 

mild severity. 

A very good compIiance to the medication was observed for both the groups. 


- - 

171

DISCUSSION 

A total of forty seven patients who Mfilled the diagnostic criteria of classical or definite 

rheumatoid arthritis were enrolled in the double blind, randomized study to compare the 

efficacy and tolerability of Sallaki (600 mg) with the routinely prescribed Diclofenac sodium 

(50 mg) in relieving symptoms of rheumatoid arthritis Eighteen patients completed the trial 

on Diclofenac sodium and fifteen patients completed the trial on Sallaki. Six patients had lost 

to follow-up after baseline assessments, four patients after one week and two patients after 

two weeks of therapy. Two of the patients had to be dropped from the study owing to 

develepment of adverse drug reaction,.and one patient was dropped after inclusion owing to 

the detection of-interstitial nephritis. 

There is a clear and well-documented evidence of efficacy of diclofenac sodium in the 

treatment of rheumatoid arthritis. The present study indicates that the eflicacy of Sallaki (600 

mg t.i d) is comparable to that of diclofenae sodium (50 mg t i.d) in relieving the symptoms 

of rheumatoid arthritis This can be concluded from the non-significant difference between 

Sallaki and jliclofenac sodium in decreasing the duration of morning stiffness, pain severity, 

number of swollen joints and the scores for swelling and tenderness in the joints. These 

objective measurements of efficacy were supported by the investigators subjective global 

evaliration of the patient's response to both the therapies 

The other two measurements of grip strength and digital joint circumference failed to show 

any evidence of efficacy. The objective value of both these parameters is subject to 

V'lfiscussion since they have no direct relationship with the inflammatory state of the joint. 

Factors such as limited mobility, increased volume and pain may influence grip strength and 

bone deformity, while exostosis and chronic swelling of the paraarticular structures may also 

affect the circumference of the digital joints 

A realistic approach to estimate the minor or major changes induced by a pharmacological 

therapy is the patient's hnctional disability. Assessment of the articular index and the 

functional index are sensitive parameters in evaluating changes induced by treatment. 

In the present study we observed a statistically significant decrease in the articular index 

(tenderness score) at the end of the study period i e four weeks in the Sallaki group The 

decrease in the articular index at the end of the study period in the diclofenac sodium group 

was however not statistically significant But comparison of the decrease in the tenderness 

score observed for both the groups revealed them not to be significantly diffe~nt from each 

other 

The results of the composite swelling score seem to indicate diclofenac sodium to be more 

efficacious than Sallaki in reducing swelling in the joints. But the baseline swelling score in 

the Sallaki group was significantly higher than the diclofenac group It was therefore decided 

to compare the decrease in the swelling score at the end of the study period for the two 

groups. The two groups were found to be comparable with each other in decreasing the 

swelling score 

Thus it may be said that a comparable positive result was obtained with both the treatments 


Thus it inay be conctuded ti-om the study that Sallaki does have a role to play in the 

pathology of rheuniatoid arthritis. The pathology of rheumatoid arthritis evolves over the 

dul-ation of tlie disease. The earliest eve18 is a nonspecific inflammatory response initiated by 

an i~nlinown stiniulus. Subsequently. an initial. and perhaps specific, response of CD4+T cell 

is induced that amplifies and perpetuates tlie intlaniniation. The presence of activated T cells 

can induce polyclonal B cell stimi~lat~on and the local production of rheumatoid factor. As 

tissue damage occurs. additional autoantigens are revealed and the nature of the T cell 

response broadens ils additional clones ofC1)3-1-T cells are recruited into the inflammatory 

site. Finall\ as n ~.csult of pel-sistent e\posiIre to tlie inflammatory milieu, the function of 

s\novial fibroblasts is altered i~nd tlley niay acquire destructive potential that no longer 

requi~.cs stimulntion fi.oni 1' cells (.II. ~iiac~.opliagcs I.' 

CI~I~IC~III,.. clironic infl;criirilatio~i in rlic s!.~io\ ial tissuc and acute inflatnmatory process in the 

s\,no\i;~l Iluid c;luses s\\clling. tcndcrness and liniitation of motion. With persistent 

i~~tl;i~it~iii~~ioti. il \;~ricty of'cli;~r.;ccter.istic dcfi)~.niitics dckclop. 

\:or manageinent of such pi~tients the various tlierapies cnlployed are directed at nonspecific 

suppression of' the inll;~nin~atory or- i~~i~~~i~i~ologic 

~xoccss in tlie hope of ameliorating 

s\.ml?to~iis and preventing progressive damage to articular structures 

'l'lie constituent of Sallaki. gum resin c\udiite oi' Boswcllin scrratn is ;I potent inhihi;:;!- .' -. 

lipoo.;spenase acti~ity 

I~iliiO~t~o~i of5-I1~~oosygcnasc acfivity prc\;cnts the synthesis of' Icucot~.ienc typf: ~i~:li~ntors of 

~ntla~n~nntion I;rom tlic family of Icucotricne-tvpc inediators lcuhotriene B., IS a ,potent 

st~~ii~rl;~to~. ol' Icucoc\~tc responses like cll~~ll~)t;~.,is. ccll adhcsiori. supcroside production. 

and can inhibit tlir acutc inllamniatory pl.ocess in the sy, lit.\, i.ii tlu~d 

cnlc~uni translocation i111d ~.clc;~sc ol' Ii\;tl~.olytic cnzymcs 

~"nnounced pl;~sni;c cs~rd;~t~ori 111 \.i\ o 

Additionally. it stimulates 

'l'lie tfec~.c;~sc ill lcndcrncss ill10 S\CCIIIII~. cli~li~i~l niani1'Cst;ilions of acute inflammation, may 

he tl~~e to tlic inliib~tion o1'5-li~~oo~~\~gcnitse ;lctivity. 

It is illso know~i fi.om cspcrinicntal studies I liat I~oswclli:~ serrat;~ cicli i~ili~bit the delayed 

In.persc~cs~t i\ 11 y react iori 

I(ccent lindings Iinve suggcstctl tIi;11 the pr.ol)ilgi~tion ol' I< A is nn irli~~i~~~iologically mediated 

cicnt. w~tli tlic inllaniniatory proccss 111 ~lic t~ssuc king cl~.~ce~i by tlic ('L)4+T cells 

~~ililt~.ar~ng tllc synoviurii 'l'lie 'I' cells p~.otl\~cc ;I variety ol' cytoLi~~cs that promote B cell 

~~~ol~f'cr;~t~o~l 

illid d~fl'C~.c~iti;~tio~i into i~~it~l)ody-li)~.~~i~~ig 

cells and tlic~.efi)~.e also may promote 

If ~ ci~l 1) ccll st in111 la1 ion 'l'lie rcsu It ant ~)~rjcluct icm 01' i~iiriirrnoglohrrli~~ and rheumatoid factor 

call Icild to 1111111111ic ~o~ii~>Ic.~ li~~.~ii;~t~o~i WI~II C(~I~SCIIII~II~ ~onlplcnient activation and 

c.\i~cc~.l>i~tio~l oftlic inflani~~ii~to~.~ 

J>I.OCCSS Oy !lie l)~.otlu~tion of'a~iapliylatoxins, C3a and C5a, 

illl(l tllc! cllc111,~tactlc fi1ct01 ('5iiI2 

'l'he tissue i~illaniniation IS I-eni~n~sccnt ol'tlclayctl type hypersensitivity reaction occurring in 

rcspu~isc to ssolublc antigens or ~iiicroorgicnis~iis 

illso tllc cylokiries rclcascd by the 'r cells, 11.- I iuid TNI; alpha play an important role by 

stiniulating the cells ol' the pannus to )~.oducc colla~enase and other neutral proteases, 

resulting in bone and cartilage destruction I2 

As the extract of Uos\~e\lia serrata srin inhibit the delaycd type hypersensitivity reactian it 

tnay be proposed that it could play a rote in preventing the persistent T cell activity and the 

subsequent cartilage and bone damage. 'I'hus Sallaki may possess disease-modifying potential 

by preventing tlie progression of the disease. 


In the present study Sallaki was better tolerated than diclofenac sodium as except for on case 

of mild dyspepsia no other incidence of GI disturbances was -observed. Clinical laboratory 

studies, performed before and after the study, never showed any pathological modification in 

both the groups. 

CONCLUSION 

The result of the study indicates Sallaki and diclofenac sodium to be having comparable 

efficacy in the treatment of symptoms of rheumatoid arthritis. However Sallaki is better 

tolerated than diclofenac sodium by the patients. Considering the fact that rheumatoid 

arthritic patients hav.e demonstrable predisposition for gastric intolerance with anti- 

inflammatory medication, we believe that Sallaki will benefit these arthritic patients who can 

not otherwise tolerate these anti-inflammatory medications. 

The result of the present study of Sallaki (600-mg t.i.d) in RA, encourage hrther 

investigations on the therapeutic potential of the drug in modifying the disease process. 

ACKNOWLEDGEMENT 

The authors wish to thank Ciufic Healthcare LM1. for providing the drug samples (Sallaki (600 

mg) and Diclofenac sodium (50 mg)) for conducting the trial. We are also grateful to Dr 

Harshad P. Thakur M.D., D.B.M. for carrying out the statistical analysis of the data. 

SELECT RESEARCH PAPERS ON EVIDENCE BASED AYURVEDIC DRUGS 1 74

Table 1. Efficacy resul'ts with Diclofenac sodium (SO mg t.i.d) in 

rheumatoid arthritis patients 

Parameter Week 0 Week 4 p < 0.05 

Vas Score 

Duration of Morning Stiffness 

Grip Strength 

Time to walk 50 ft 

Digital Joint Circumference 

Total Swelling Score 

No. of Swollen Joints 

Total Tenderness score 

No. of Tender Joints 

57.71 k 23.7 44.06 i 25 S 

Values are expressed as the mean score * std. deviation 

Number of observations = 18 


175

Table 2. Efficacy results with Sallaki (600 mg ti.d) in rheumatoid arthritis patients 

Parameter Week 0 Week 4 p< 0.05 

Vas Score 66.14*28.03 48.57*27.49 S 

Durati6n of Morning Stiffness 

Grip Strength 

Time to walk 50 ft 

Digital Joint Circumference 

Total Swelling Score 

No. of Swdlen Joints 

Total Tenderness score 

No. of Tender Joints 

Values are expressed as mean score + std deviation 



Table 3 . Comparison of Diclofenac sodium (50 mg t.i.d) with Sallaki (600 mg t.i.d) 

therapy in rheumatoid arthritis patients 

Parameter Diclofenac Sallaki P 

sodium 

Vas Score 21.42A22.06 24.63k22.9 NS 

Duration of Morning Stiffness 44.84 k 42.7 38.53 * 40.29 NS 

Grip Strength 23.24 * 18.3 39.73 f 37.9 NS 

Time to walk 50 ft 12.47 k 11.05 11.98 f 12.3 NS 

Digital Joint Circumference 0.83 * 0.82 2.41 =t 5.58 NS 

Total Swelling Score 4.71f 3.92 9.25 % 8.9 NS 

No. of Swollen Joi-nts 4.71 * 4.36 7.59 =t 6.10 NS 

Total Tenderness score 11.92 f 9.85 12.59 f 12.5 NS 

No. of Tender Joints 7.92 * 6.71 7.56 k 8.28 NS 

Valyes expressed are the mean absolute difference between the Week 0 score and Week 4 

score for each parameter 

Values are expressed as mean * std. deviation 


Table 4. Mean of laboratory tests in 15 patients sumring from RA. given 

Sallaki (600 m t.i.d) for four weeks 


Hemoglobin 11.83 * 2.13 10.5 * 1.34 NS 

WBC 

Fasting Blood Sugar 

Blood Urea Nitrogen 

Serum Creatinine 

Serum Bilirubin 

SGPT 

Serum Total Protein 

Albumin 

Globulin 

Values are expressed as mean std. deviation 



Table 5. Mean of laboratory tests in 18 patients suffering from R.A. 

given Diclofenac sodium (50 mg t.i.d) for four weeks 


Hemoglobin 11.81* 1.59 12.00 h 1.64 NS 

WBC 8193.3*2364 7486.6*2071 NS 

Fasting Blood Sugar 87.69 k 29.1 89.04k149 NS 

Blood Urea Nitrogen 13.87 * 15.16 9.93 * 3 7 NS 

SGPT 29.09 k 13.06 42.27 * 39.5 NS 

Serum Total Protein 7.4 * 0.92 11.27i13.08 NS 

Albumin 3.7 * 0.82 3.0k 1.52 NS 

Globulin 2.6* 1.31 2.2 5 1.64 NS 

Values are expressed as mean .t std. deviation 


-- - -- 


Table 6. Overall efficacy and overall tolerability to treatment for four weeks with 

Sallaki (600 mg t.i.d) and Diclofenac sodium (50 mg t.i.d) 

Treatment Responses to Overall Efficacy Responses to Overall Tolerability 

Good Fair Poor Good Fair Poor 

Sallaki 1 7 7 2 12 4 

Diclofenac 12 

Values expressed are the number of patients reporting the responses 

SELECT RESEARCH PAPEKS ON EVIDENCE BASED AYURVEDIC DRUGS 180

REFERENCES 

I. Malaviya, A.N., Kaushik, P. ''Recent udvances in drug therapy for rheumatoid arthrltis" 

Journal of Association of Physicians of India September 1999, V01. 47, pp 912-91 7 

2. Jhaj, R., Uppal. R, et al. "Adverse drug reactions with anti-rheumatic hgs in a 

Rheumafology clinic" Journal of Indian Rheumatism Association 1998, Vol. 6 No 1, 

pp 3-6. 

3. Atal, C.K., et d. Indian Journal of Pharmacology 1980, Vol 12, No 10 pp 59. 

4. Singh, G.B., Atal, C.K. "Pharmacology of an extract of salul guggal ex-Boswella serruta, 

a new non-steroiclal anti-inflammatory agent" Agents and actions 1986, Vol. 18, pp407- 

411. 

5. Arnmon, H.P.T., Mack, T., et al. "Inhibition of leukotriene b4 formation m rat pertioneul 

neutrophils by ethanolrc extract of the gum resin exuhte of -Boswellru serruta" Planta 

Medica 1991, 57, pp 203-207. 

6 Sharma, M.L., Kaul, A,, et al 'lmmunomodulutory activzty of Bo~we[/zc UCZ& 

(penta~yclic triterpene acids) jkom Boswellia serratu ". Phy to therapy Research, 1 996, 

VO~ 1 O(2)' p 107- 1 12. 

7 Menon, M K., Kar, A "Analgesic and psychophurmacologzcul effects of the gum resrn 

em~hte uf -Boswellza serruta " Planta Medica 197 1, 1 9, pp 333-34 1 

8 Chandrashekaran A N., et al. "Efect of S'allakz m the treatment of Hheumatozd arthrltis " 

JIM, 1995, VOI 3 - NO. 3, pp101-106. 

9 Rajagopal, S., et al. "Assessment of the therapeutic effect of ";allakz (Boswellru serrataj zn 

the treutment ofjuvenile rheumatold urthritrs " JIRA, 1995, Vol 3 - No 3, pp 107- 1 1 0 

I0 Lohokare, S. K "A C/inzcal Trzul of Boswellzu Serruta (Sallukl) In the treatment of 

Osteoarthrztzs." JIRA, 1995, Vol. 3 - No 3, 1 13- 1 16 

11. Arnett, F C. et al. "The American Rheumatism Associatran 1987 revised criterza for the 

cls,sz$cution qf rheumatold urthntls" Arthritis Rheum 1988 3 1, pp3 15-324 

12.Lipsky1 P.E., "Rheumatoid Arthritis" in Harrison's Principles of Internal 

medicine, 14'~ ~dition, Mac Graw Hill Companies, Inc. 1998, pp. 1880-1 888 

- 


August, 20,1999 

To, 

Dr. (Mrs) L.S. Bichile, M.D. 

Professor and Head Department of Medicine & 

Chief Rheumatology, 

K E M Hospital, 

Parel, 

Mumbai- 400 012. 

Sub: Receipt of the completed case report forms and the drug supply returned by the 

patients 

Dear Dr. Bichile, 

We gratefully acknowledge the receipt of twenty-two completed case report forms of the 

patients enrolled in the trial namely "Clinical trial to evaluate the eficacy of Sallaki 600 mg 

in pat~ents with rheumatoid arthritis" and bearing the patient number (1-10,12-15,17,21-26). 

Amongst these, 13 case report forms of the patients bearing the patient number as mentioned 

below are complete for all the follow up visits i e 4 weeks 

PatientNo 1,2,3,4,5,6,8, 10, 12, 17,248~26 

Six of the case report forms of the patients bearing the patient number as mentioned below 

are not complete for all the follow-ups as the patient's lost to follow-up. 

Patient No. 9, 13, 14, 15,22,25 

Two case report forms as mentioned below have been filled for adverse drug reactions 

Patient No 7,23 

One case report form has stated the patient's discontinuation from the study 

Patient No. 21. 

The drugs returned by the patients bearing the patient number (1-10, 12-15, 17) was collected 

back from the site on 3 0 June, ~ 1999 for subsequent.disposition. 

The drugs returned by the patients bearing the patient number (21-26) will be collected back 

from the site for subsequent disposition today. 

Thanking you once again for your kind cooperation 

Yours truly, 

For SPC Interface 

Dr. H.S. Parikh M.D. 

SELECT RESEARCH PAPERS ON kvIDENCE BASED AYURVEDIC DRUGS 182

To, 




K.E.M. Hospital, 

Parel, 

Mumbai- 400 012. 


patients 


We gratehlly acknowledge the receipt of thirteen completed case report forms of the patients 

enrolled in the trial namely "Clinical trial to evaluate the eficacy of Sallaki 600 mg in 

patients with rheumatoid arthritis" and bearing the patient number (1 1, 16, 18-20, 27-34). 

Amongst these, 12 case report forms ot'the patients bearing the patient number as mentioned 

below are complete for all the follow up visits i.e. 4 weeks 

Patient No 1 1, 16, 18, 1 9, 20, 27, 28, 29, 3 1, 32, 33 

One of the case report form of the patients bearing the patient number as mentioned below I e 

not complete for all the follow-ups as the patient lost to follow-up. 

Patient No. 30 

Two case report forms as mentioned below have been filled for adverse drug reactions 

Patient No. 34, 

The drugs returned by the patients bearing the patient number (1 1, 16, 18-20, 27-34) will be 

collected back from the site for subsequent disposition today. 

Thanking you once again for your kind cooperation 

Yours truly, 




183

February 25, 2000 

To, 




K.E.M Hospital, 

Parel, 

Mumbai- 400 0 12. 


patients 


We gratefully acknowledge the receipt of nine completed case report forms of the patients 

enrolled in the trial namely "Clinical trial to evaluate the efficacy of Sallaki 600 mg in 

patients with rheumatoid arthritis" aiid bearing the patient number (35-43). 


below are complete for all the follow up visits i.e. 4 weeks 

Patient No. 36, 37, 38, 39, 41 & 42 

Three of the case report forms of the patients-bearing the patient number as mentioned below 


Patient No 35, 40, 43 



Thanking you once again for your kind cooperation. 

Yours truly, 




March 3 1, 2000 

To, 




K.E.M. Hospital, 

Parel, 

Mumbai- 400 012 


pa tien ts 


We gratehlly acknowledge the receipt of four completed case report forms of the patients 

enrolled in the trial namely "Clinical trial to evaluate the efficacy of Sallaki 600 mg in 

patients with rheumatoid arthritis" and bearing the patient number (44-47). 


below are complete for a11 the follow up visits i.e. 4 weeks 

Patient No. 44,45 & 46 

Three of the case report forms of the patients bearing the patient number as mentioned below 


Patient No. 47 



Thanking you once again for your kind cooperation. 

Yours truly, 




185

June 28;2000 

To, 



Chief Wheumatology, 

K E.M Hospital, 

Parel, 

Murnbai- 400 012. 

Sub: Receipt of the report of the clinical trial 

Dear Dr. B.ichile, 

We are extremely pleased to receive the report entitled "Double-blind randomized controlled 

trial of Sallaki (600 mg) vs Diclofenac (50 mg) in the treatment of rheumatoid arthritis" of 

the clinical trial conducted by your department. 

We also take this opportunity to once again express our gratitude at receiving 47 completed 

case report forms of the patient you had enrolled in the trial. 

We would like to reiterate for your perusal that amongst the 47 patients you had enrolled in 

the trial, 33 patients completed the four weeks of the trial, 3 reported for adverse drug 

reaction and 1 1 lost to follow up. 

The balance payment for the remaining case report forms will be made at the earliest 

Thanking you once again for the well-conduction of the trial 

Yours truly, 




Economic and 

Medicinal Plant Research 

Volume 5 

Edited by 

H. WAGNER 

Institut fur Pharm~utische Biologic der Unkmsitiit Miimhn, .lfGn~hcrl, 

il >st Cennary 

NORMAN R. FARNSWORTH 

Program for Cqllaborative Research in the Pharmaceutical ;ciencis: College 

oj Pharmacy, University of Illinois at Ckgo, Chicagoy Illinoisy ~h.4 

ACADEMIC PRESS 

Harcouri Brm Jovanooitlr, Publirhcrs 

London San Die New York 

Boston Sydney ?? okyo Toronto 

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