Prior Authorization Guideline - OptumRx

Prior Authorization Guideline 

Guideline: M-Plan Inj - Remicade 

Therapeutic Class: Miscellaneous 

Therapeutic Agents 

Therapeutic Sub-Class: Disease-modifying 

Antirheumatic Drugs (Remicade) 

Client: M-Plan Inj 

Approval Date: 8/2/2005 Revision Date: 12/5/2006 

I. BENEFIT COVERAGE 

Remicade (infliximab) 

II. 

INDICATIONS 

A. FDA Approved Indications 1 

1. Rheumatoid Arthritis (RA) 

Remicade, in combination with methotrexate, is indicated for reducing signs and 

symptoms, inhibiting the progression of structural damage, and improving physical 

function in patients with moderately to severely active rheumatoid arthritis. 

2. Crohn’s Disease (CD) 

a. Remicade is indicated for reducing signs and symptoms and inducing and 

maintaining clinical remission in adult and pediatric patients with moderately to 

severely active Crohn’s disease who have had an inadequate response to 

conventional therapy. 

b. Remicade is indicated for reducing the number of draining enterocutaneous and 

rectovaginal fistulas and maintaining fistula closure in adult patients with 

fistulizing Crohn’s disease. 

3. Ankylosing Spondylitis (AS) 

Remicade is indicated for reducing signs and symptoms in patients with active 

ankylosing spondylitis. 

4. Psoriatic Arthritis (PsA) 

Remicade is indicated for reducing signs and symptoms of active arthritis in patients 

with psoriatic arthritis.

5. Ulcerative Colitis (UC) 

Remicade is indicated for reducing signs and symptoms, achieving clinical remission 

and mucosal healing, and eliminating corticosteroid use in patients with moderately to 

severely active ulcerative colitis who have had an inadequate response to 

conventional therapy. 

6. Plaque Psoriasis 

Remicade indicated for the treatment of adult patients with chronic severe (i.e., extensive 

and or disabling) plaque psoriasis who are candidates for systemic therapy and when 

other systemic therapies are medically less appropriate. Remicade should only be 

administered to patients who will be closely monitored and have regular follow-up visits 

with a physician. 

III. 

GUIDELINE 

A. Rheumatoid Arthritis 

1. Initial treatment of RA 

a. Remicade will be approved for adult patients with RA based on all of the following 

criteria: 

(1) For patients ≥ 18 years old who have moderate to severe active RA as 

defined by all the following 1, 2 

(a) 

(b) 

(c) 

(d) 

At least 6 swollen joints; AND 

At least 6 tender/painful joints; AND 

More than 45 minutes of morning stiffness; AND 

Elevated C-reactive protein (CRP) or erythrocyte sedimentation rate 

(ESR) unless patient is on corticosteroids 

-AND- 

(2) Prescribed or recommended by a rheumatologist 

-AND- 

(3) One of the following 

(a) Patient is concurrently on methotrexate 1 

-OR- 

(b) 

Documented treatment failure (with doses of 20 mg/week), 

contraindication, or intolerance to methotrexate. 3,4,a 

-OR- 

(c) 

Documented treatment failure, contraindication or intolerance to two or 

more of the following DMARDs for at least 3 months 2,5

(i) Azathioprine (Imuran ® ) 

(ii) Cyclosporine (Sandimmune ® , Neoral ® , Gengraf ® ) 

(iii) Gold compounds (Aurolate ® , Myochrysine ® , Riduara ® , Solganal ® ) 

(iv) Hydroxychloroquine (Plaquenil ® ) 

(v) Leflunomide (Arava ® ) 

(vi) Penicillamine (Cuprimine ® ) 

(vii) Sulfasalazine (Azulfidine ® ) 

-AND- 

(4) Verification that patient has been evaluated for tuberculosis and treated 

1, 2, * 

accordingly 

-AND- 

(5) Remicade will not be approved for use in combination with anakinra (Kineret) 

1, 5 

Initial authorization will be issued for 6 months 

*Refer to contraindications and warning section for list of additional at-risk 

infections 

2. Re-authorization criteria for the treatment of RA 

a. Remicade will be approved for continuation of therapy based on one of the 

following criteria: 

(1) Both of the following: 

(a) At least 20% improvement in the tender and swollen joint count 2,6 

-AND- 

(b) At least 20% improvement in three of the following: 2,6 

(i) Patient’s global assessment 

(ii) Physician’s global assessment 

(iii) Patient’s assessment of pain 

(iv) Degree of disability 

(v) Acute phase reactant (ESR or CRP) concentration 

-OR- 

(2) Submission of chart documentation demonstrating the clinical equivalent of the 

above criteria 

Re-authorization of therapy will be issued for 12 months. Re-evaluation will be 

requested every year for further determination of coverage. 

B. Adult Crohn's Disease 

1. Initial treatment of adult Crohn’s disease 

a. Remicade will be approved based on all of the following criteria:

(1) For patient ≥ 18 years old with moderate to severe Crohn's disease defined by 

the Crohn's Disease Activity Index (CDAI) between 220 and 400 1,7, b 

-AND- 

(2) Patients who have demonstrated inadequate response to one or more of the 

following medication(s): 

(a) Corticosteroids for at least 8 weeks; 7,8 OR 

(b) 6-mercaptopurine (Purinethol ® ) for at least 6 months; 7, 8 OR 

(c) Azathioprine (Imuran ® ) for at least 6 months; 7,8 OR 

(d) Methotrexate for at least 12 weeks 7 OR 

-AND- 


accordingly 1 * 

-AND- 

(4) Prescribed or recommended by a gastroenterologist 

Authorization will be approved for 8 weeks (a total of 3 infusions). 1 


infections. 

2. Re-authorization criteria for the treatment of adult Crohn’s disease 



(1) Patient has demonstrated response to Remicade therapy (a decrease of 70 or 

more points in the CDAI score) 1,7, 9 

-OR- 

(2) Submission of chart documentation demonstrating the clinical equivalent of 

the above criteria. 

Re-authorization of therapy will be issued for 12 months. 1 

C. Pediatric Crohn’s disease 

1. Initial treatment of pediatric Crohn’s disease 

a. Remicade will be approved based on all of the following criteria: 

(1) For patient ≥ 6 years old with moderately to severely active Crohn's disease 

defined by the Pediatric Crohn's Disease Activity Index (PCDAI) score ≥ 30 1 

-AND-

(2) Patients who have demonstrated inadequate response to one or more of the 

following medication(s): 1 

(a) Corticosteroids; OR 

(b) 6-mercaptopurine (Purinethol ® ); OR 

(c) Azathioprine (Imuran ® ); OR 

(d) Methotrexate 

-AND- 



-AND- 


Authorization will be issued for 8 weeks (a total of 3 infusions). 1, c 


infections. 

2. Re-authorization criteria for the treatment of pediatric Crohn’s disease 



(1) Patient has demonstrated response to Remicade therapy (a decrease from 

baseline in PCDAI score of ≥15); 1 

-OR- 



Re-authorization of therapy will be issued for 12 months. 1 

D. Fistulizing Crohn's Disease 

1. Initial treatment of FCD 


(1) Patient ≥ 18 years old with a single or multiple draining fistulas, including 

perianal and enterocutaneous, for at least 3 months duration 1,9,10 

-AND- 

(2) Patients on concomitant therapies or have failed concomitant therapies 

with at least one of the following 9,10 

(a) 6-mercaptopurine (Purinethol); OR 

(b) Azathioprine (Imuran); OR 

(c) Antibiotics (i.e., Flagyl ® , fluoroquinolone); OR 

(d) Oral corticosteroids; OR

(e) Methotrexate 

-AND- 



-AND- 


Initial authorization will be issued for 8 weeks for a total of 3 infusions. 


infections. 

2. Re-authorization criteria for the treatment of FCD 

a. Remicade will be approved for continuation of therapy based on the following 

criterion: 

(1) Patient has demonstrated response to Remicade therapy (i.e., maintaining 

fistula closure, a reduction of ≥ 50% in the number of draining fistulas from 

baseline) 1,9,10 

-OR- 



Re-authorization for therapy will be issued for 12 months. 

E. Ankylosing Spondylitis (AS) 

1. Initial treatment of ankylosing spondylitis 

a. Remicade will be approved for the treatment of ankylosing spondylitis based on 

all of the following criteria: 

(1) Diagnosis of ankylosing spondylitis based on the modified New York criteria 

as follows: 11,12 

(a) Radiologic criterion: Sacroiliitis (≥ grade II bilaterally or grade III-IV 

unilaterally) confirmed by x-ray of the pelvis 11 

-AND- 

(b) At least two of the following clinical criteria: 11 

(i) Low back pain and stiffness > 3 months that improves with 

exercise but is not relieved by rest; OR 

(ii) Limitation of motion of the lumbar spine in both the sagittal and 

frontal planes; OR 

(iii) Limitation of chest expansion relative to normal values 

correlated for age and sex

-AND- 

(2) Evidence of active disease as defined by two BASDI (Bath Ankylosing 

Spondylitis Disease Activity Index) scores > 4 (scale 0-10); scores must be 

obtained at least one month apart. 

-AND- 


-AND- 

(4) Documented treatment failure, contraindication, or intolerance to two or 

more NSAIDs for at least 3 months 11,12 

-AND- 

(5) One of the following (except in axial disease): 11 

(a) For patients with symptomatic peripheral disease, documented 

treatment failure, contraindications, or intolerance to at least one local 

corticosteroid injection and sulfasalazine (Azulfidine) up to 3 g/day (or a 

maximum tolerated dose) for 4 months; OR 

(b) For patients with symptomatic enthesitis, documented treatment 

failure, contraindications, or intolerance to appropriate local 

treatment; OR 

(c) For patients with persistent peripheral arthritis, documented 

treatment failure, contraindication, or intolerance to sulfasalazine 

(Azulfidine) up to 3 g/day (or maximum tolerate dose) for 4 months 

-AND- 



Initial authorization will be issued for 8 weeks (a total of 3 infusions). 1,11 


infections. 

2. Re-authorization criteria for ankylosing spondylitis 



(1) A positive response to therapy defined by a 50% relative change or absolute 

change of 2 (scale 0-10) in BASDAI score from baseline 11 

-OR- 

(2) Documentation of clinical improvement from the ongoing therapy with 

Remicade.

Re-authorization for therapy will be issued for 12 months. 

F. Psoriatic Arthritis (PsA) 

1. Initial treatment of PsA 

a. Remicade will be approved for PsA based all of the following criteria: 

(1) For patients ≥ 18 years old who have active disease as defined by all the 

1, 13 

following 

(a) 

(b) 

(c) 

(d) 

At least 3 swollen joints; AND 

At least 3 tender/painful joints; AND 

More than 45 minutes of morning stiffness; AND 

Elevated C-reactive protein (CRP ≥ 15 mg/liter) or erythrocyte 

sedimentation rate (ESR ≥ 28 mm/hour) unless patient is on 

corticosteroids) 

-AND- 


-AND- 

(3) Documented treatment failure, contraindication, or intolerance to two or 

more of the following DMARDs for at least 3 months: 13 

(a) Azathioprine (Imuran ® ); OR 

(b) Cyclosporine (Sandimmune ® ); OR 

(c) Gold Compounds (e.g., Aurolate ® , Myochrysine ® , Ridaura ® , 

Solganal ® ); OR 

(d) Hydroxychloroquine (Plaquenil ® ); OR 

(e) Leflunomide (Arava ® ); OR 

(f) Penicillamine (Cuprimine ® ); OR 

(g) Sulfasalazine (Azulfidine ® ); OR 

(h) Methotrexate 

-AND- 


accordingly 1* 

-AND- 

(5) Remicade will not be approved for use in combination with anakinra 

(Kineret); 1 

Initial authorization will be issued for 6 months 

*Refer to contraindications and warning section for a list of additional atrisk 

infections. 

2. Re-authorization criteria for the treatment of PsA

a. Remicade will be approved for continuation of therapy based one of the 

14, 15 

following criteria 

(1) Both of the following: 

(a) 

(b) 

At least 20% improvement in the tender and swollen joint count; AND 

At least 20 percent improvement in three of the following: 

(i) Patient’s global assessment 

(ii) Physician’s global assessment 

(iii) Patient’s assessment of pain 

(iv) Degree of disability 

(v) Acute phase reactant (ESR or CRP) concentration 

-OR- 

(2) Submission of chart documentation demonstrating the clinical equivalent to the 

above criteria. 

Re-authorization for therapy will be issued for 12 months. Re-evaluation will be 

requested every year for further determination of coverage. 

G. Ulcerative Colitis 

1. Remicade will be based on all of the following criteria: 

a. Confirmed diagnosis of moderate to severe ulcerative colitis 1 

-AND- 

b. Documented treatment failure, contraindication or intolerance to one of the following 

conventional therapy: 16 

(1) Corticosteroids (e.g., prednisone, methylprednisone); OR 

(2) 5-aminosalicylic acid (5-ASA) products (e.g., mesalamine [Asacol ® , Pentasa ® , 

Rowasa ® ], osalazine [Dipentum ® ], sulfasalazine [Azulfidine ® , Sulfazine ® ]); OR 

(3) Azothioprine (Imuran ® ); OR 

(4) 6-mercaptopurine (Purinethol ® ); OR 

(5) Cyclosporine (Neoral ® , Sandimmune ® , or Gengraf ® ) 

-AND- 

c. Prescribed by a gastroenterologist or by gastroenterologist consult 16 

-AND- 

d. Verification that patient has been evaluated for tuberculosis and treated accordingly* 

Authorization will be issued for 12 months. 17 Re-evaluation will be requested every 

year for further determination of coverage. 

*Refer to contraindications and warning sections for list of additional at-risk 

infections.

H. Plaque Psoriasis 

1. Initial treatment of chronic moderate to severe plaque psoriasis 


(1) Diagnosis of moderate to severe chronic (>6 months) plaque psoriasis in 

patients ≥ 18 years of age involving a minimum body surface of 10%; 1 

-AND- 

(2) Failure or intolerance to both of the following conventional therapies: 1 

(a) 

Phototherapy with at least one of the following: 

(i) Ultraviolet Light B (UVB) used alone or in combination with 

topical or systemic treatments; OR 

(ii) Pulse Dye Laser; OR 

(iii) Psoralen and exposure to ultraviolet light A (PUVA); OR 

(iv) Photochemotherapy 

-AND- 

(b) 

Systemic therapy with at least one of the following: 

(i) Methotrexate (Rheumatrex ® , Trexall ® ); OR 

(ii) Cyclosporine (Sandimmune ® , Neoral ® , Gengraf ® ); OR 

(iii) Acitretin (Soriatane ® ); OR 

(iv) Hydroxyurea (Hydrea ® ); OR 

(v) Sulfasalazine (Azulfidine ® ); OR 

(vi) 6-thioguanine (Purinethol ® ); OR 

(vii) Mycophenolate (Cellcept ® ) 

-AND- 

(3) Prescribed or recommended by a dermatologist; 

-AND- 


accordingly; 

Initial authorization will be issued for 3 months 1 

2. Re-authorization criteria for chronic moderate to severe plaque psoriasis 

a. Remicade will be approved for continuation of therapy based on all of the 


(1) Patient has achieved a scoring of “minimal” or “clear” by static Physician 

Global Assessment (sPGA) 1 

-OR-

(2) Documentation of clinical improvement from the ongoing therapy with 

Remicade 

Re-authorization for therapy will be issued for 12 months d 

IV. 

CONTRAINDICATIONS AND WARNINGS 

A. Contraindications 1 

Remicade at doses >5 mg/kg should not be administered to patients with moderate to 

severe heart failure. In a randomized study evaluating Remicade in patients with moderate 

to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), 

Remicade treatment at 10 mg/kg was associated with an increased incidence of death and 

hospitalization due to worsening heart failure 

Remicade should not be administered to patients with known hypersensitivity to any 

murine proteins or other component of the product. 

B. Warnings 1 

1. Black Box Warning 

Risk of Infections 

Patients treated with Remicade are at increased risk far infections, including progression 

to serious infections leading to hospitalization or death. These infections have included 

bacterial sepsis, tuberculosis, invasive fungal and other opportunistic infections. Patients 

should be educated about the symptoms of infection, closely monitored far signs and 

symptoms of infection during and after treatment with Remicade, and should have 

access to appropriate medical care. Patients who develop an infection should be 

evaluated far appropriate antimicrobial therapy and far serious infections, Remicade 

should be discontinued. 

Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation) has 

been observed in patients receiving Remicade. Patients should be evaluated far 

tuberculosis risk factors and be tested far latent tuberculosis infection prior to initiating 

Remicade and during therapy. Treatment of latent tuberculosis infection should be 

initiated prior to therapy with Remicade. Treatment of latent tuberculosis in patients 

with a reactive tuberculin test reduces the risk of tuberculosis reactivation in patients 

receiving Remicade. Same patients who tested negative far latent tuberculosis prior to 

receiving Remicade have developed active tuberculosis. Physicians should monitor 

patients receiving Remicade far signs and symptoms of active tuberculosis, including 

patients who tested negative far latent tuberculosis infection. 

Hepatosplenic T-cell lymphomas 

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been reported in 

adolescent and young adult patients with Crohn’s disease treated with Remicade. This 

rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. 

All of these hepatosplenic T-cell lymphomas with Remicade have occurred in patients 

on concomitant treatment with azathioprine or 6-mercaptopurine. 

2. Risk of infections

Serious infections, including sepsis and pneumonia, have been reported in patients 

receiving TNF-blocking agents. Some of these infections have been fatal. Many of 

the serious infections in patients treated with Remicade have occurred in patients on 

concomitant immunosuppressive therapy that, in addition to their Crohn’s disease or 

rheumatoid arthritis, could predispose them to infections. 

Remicade should not be given to patients with a clinically important, active infection. 

Caution should be exercised when considering the use of Remicade in patients with a 

chronic infection or a history of recurrent infection. Patients should be monitored for 

signs and symptoms of infection while on or after treatment with Remicade. New 

infections should be closely monitored. If a patient develops a serious infection, 

Remicade therapy should be discontinued. 

Cases of tuberculosis, histoplasmosis, coccidioidomycosis, listeriosis, pneumocystosis, 

other bacterial, mycobacterial and fungal infections have been observed in patients 

receiving Remicade. Patients should be evaluated far tuberculosis risk factors and be 

tested far latent tuberculosis infection. Treatment of latent tuberculosis infections should 

be initiated prior to therapy with Remicade. When tuberculin skin testing is performed for 

latent tuberculosis infection an induration size of 5 mm or greater should be considered 

positive, even if vaccinated previously with Bacille Calmette-Guerin (BCG). 

Patients receiving Remicade should be monitored closely far signs and symptoms of 

active tuberculosis, particularly since tests far latent tuberculosis infection maybe falsely 

negative. The possibility of undetected latent tuberculosis should be considered, 

especially in patients who have immigrated from or traveled to countries with a high 

prevalence of tuberculosis or had close contact with a person with active tuberculosis. All 

patients treated with Remicade should have a thorough history taken prior to initiating 

therapy. Same patients who have previously received treatment far latent or active 

tuberculosis have developed active tuberculosis while being treated with Remicade. Antituberculosis 

therapy should be considered prior to initiation of Remicade in patients with 

a past history of latent or active tuberculosis in whom an adequate course of treatment 

cannot be confirmed. Anti-tuberculosis therapy prior to initiating Remicade should also 

be considered in patients who have several or highly significant risk factors far 

tuberculosis infection and have a negative test far latent tuberculosis. The decision to 

initiate anti-tuberculosis therapy in these patients should only be made following 

consultation with a physician with expertise in the treatment of tuberculosis and taking 

into account bath the risk far latent tuberculosis infection and the risks of antituberculosis 

therapy. 

For patients who have resided in regions where histoplasmosis or coccidioidomycosis is 

endemic, the benefits and risks of Remicade treatment should be carefully considered 

before initiation of Remicade therapy. 

Serious infections were seen in clinical studies with concurrent use of anakinra and 

another TNFα-blocking agent, etanercept, with no added clinical benefit compared to 

etanercept alone. Because of the nature of the adverse events seen with combination 

of etanercept and anakinra therapy, similar toxicities may also result from the 

combination of anakinra and other TNF-α blocking agent. Therefore, the combination 

of Remicade and anakinra is not recommended. 

3. Hepatosplenic T-cell lymphomas 

Rare postmarketing cases of hepatosplenic T-cell lymphoma have been reported in 

adolescent and young adult patients with Crohn’s disease treated with Remicade. This 

rare type of T-cell lymphoma has a very aggressive disease course and is usually

fatal. All of these hepatosplenic T-cell lymphomas with Remicade have occurred in 

patients on concomitant treatment with azathioprine or 6-mercaptopurine. 

4. Hepatotoxicity 

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and 

cholestasis have been reported rarely in postmarketing data in patients receiving 

Remicade. Autoimmune hepatitis has been diagnosed in some of these cases. 

Severe hepatic reactions occurred between two weeks to more than a year after 

initiation of Remicade; elevations in hepatic aminotransferase levels were not noted 

prior to discovery of the liver injury in many of these cases. Some of these cases were 

fatal or necessitated liver transplantation. Patients with symptoms or signs of liver 

dysfunction should be evaluated for evidence of liver injury. If jaundice and/or 

marked liver enzyme elevations (e.g., ≥ 5 times the upper limit of normal) develops, 

Remicade should be discontinued, and a thorough investigation of the abnormality 

should be undertaken. As with other immunosuppressive drugs, use of Remicade has 

been associated with reactivation of hepatitis B in patients who are chronic carriers of 

this virus (i.e., surface antigen positive). Chronic carriers of hepatitis B should be 

appropriately evaluated and monitored prior to the initiation of and during treatment 

with Remicade. In clinical trials, mild or moderate elevations of ALT and AST have 

been observed in patients receiving Remicade without progression to severe hepatic 

injury. 

5. Patients with heart failure 

Remicade has been associated with adverse outcomes in patients with heart failure, 

and should be used in patients with heart failure only after consideration of other 

treatment options. The results of a randomized study evaluating the use of Remicade 

in patients with heart failure (NYHA Functional Class III/IV) suggested higher 

mortality in patients who received 10 mg/kg Remicade, and higher rates of 

cardiovascular adverse events at doses of 5 mg/kg and 10 mg/kg. There have been 

postmarketing reports of worsening heart failure, with and without identifiable 

precipitating factors, in patients taking Remicade. There have also been rare 

postmarketing reports of new onset heart failure, including heart failure in patients 

without known pre-existing cardiovascular disease. Some of these patients have been 

under 50 years of age. If a decision is made to administer Remicade to patients with 

heart failure, they should be closely monitored during therapy, and Remicade should 

be discontinued if new or worsening symptoms of heart failure appear. 

6. Hematologic events 

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a 

fatal outcome, have been reported in patients receiving Remicade. The causal 

relationship to Remicade therapy remains unclear. Although no high-risk group(s) has 

been identified, caution should be exercised in patients being treated with Remicade 

who have ongoing or a history of significant hematologic abnormalities. All patients 

should be advised to seek immediate medical attention if they develop signs and 

symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever) while on 

Remicade. Discontinuation of Remicade therapy should be considered in patients who 

develop significant hematologic abnormalities. 

7. Hypersensitivity

Remicade has been associated with hypersensitivity reactions that vary in their time of 

onset and required hospitalization in some cases. Most hypersensitivity reactions, 

which include urticaria, dyspnea, and/or hypotension, have occurred during or within 

2 hours of Remicade infusion. However, in some cases, serum sickness-like reactions 

have been observed in Crohn’s disease patients 3 to 12 days after Remicade therapy 

was reinstituted following an extended period without Remicade treatment. Symptoms 

associated with these reactions include fever, rash, headache, sore throat, myalgias, 

polyarthralgias, hand and facial edema, and/or dysphagia. 

These reactions were associated with marked increase in antibodies to Remicade, loss 

of detectable serum concentrations of Remicade, and possible loss of drug efficacy. 

Remicade should be discontinued for severe reactions. Medications for the treatment 

of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids 

and/or epinephrine) should be available for immediate use in the event of a reaction. 

8. Neurologic events 

Remicade and other agents that inhibit TNF have been associated in rare cases with 

optic neuritis, seizure, and new onset or exacerbation of clinical symptoms and/or 

radiographic evidence of central nervous system demyelinating disorders, including 

multiple sclerosis, and CNS manifestation of systemic vasculitis. Prescribers should 

exercise caution in considering the use of Remicade in patients with pre-existing or 

recent onset of central nervous system demyelinating or seizure disorders. 

Discontinuation of Remicade should be considered in patients who develop significant 

central nervous system adverse reactions. 

9. Malignancies 

In the controlled portions of clinical trials of some TNF-alpha blocking agents 

including Remicade, more malignancies have been observed in patients receiving 

TNF-blockers compared with control patients. During the controlled portions of 

Remicade trials in patients with moderately to severely active rheumatoid arthritis, 

Crohn's disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis, 14 

patients were diagnosed with malignancies among 2897 Remicade treated patients vs. 

1 among 1262 control patients (at a rate of 0.65/100 patient-years among Remicadetreated 

patients vs. a rate of 0.13/100 patient-years among control patients), with 

median duration of follow-up 0.5 years for Remicade-treated patients and 0.4 years for 

control patients. Of these, the most common malignancies were breast, colorectal, and 

melanoma. The rate of malignancies among Remicade-treated patients was similar to 

that expected in the general population whereas the rate in control patients was lower 

than expected. 

In the controlled portions of clinical trials of all the TNF-alpha-blocking agents, more 

cases of lymphoma have been observed among patients receiving a TNF blocker 

compared with control patients. In the controlled and open-label portions of Remicade 

trials, 4 patients developed lymphoma among 4292 patients treated with Remicade 

(median duration of follow-up 1.0 years) vs. 0 lymphomas in 1265 control patients 

(median duration of follow-up 0.5 years). In patients with rheumatoid arthritis, 2 

lymphomas were observed for a rate of 0.08 cases per 100 patient years of follow-up, 

which is 3-fold higher than expected in the general population. In the combined 

clinical trial population for rheumatoid arthritis, Crohn's disease, psoriatic arthritis, 

ankylosing spondylitis, and ulcerative colitis, 4 lymphomas were observed for a rate 

of 0.11 cases per 100 patient-years of follow-up, which is approximately 5-fold higher 

than expected in the general population. Patients with Crohn’s disease or rheumatoid 

arthritis, particularly patients with highly active disease and/or chronic exposure to

immunosuppressant therapies, may be at a higher risk (up to several fold) than the 

general population for the development of lymphoma, even in the absence of TNFblocking 

therapy. 

In a clinical trial exploring the use of Remicade in patients with moderate to severe 

chronic pulmonary disease (COPD), more malignancies, the majority of lung or head 

and neck origin, were reported in Remicade treated patients compared with control 

patients. All patients had a history of heavy smoking. Prescribers should exercise 

caution when considering the use of Remicade in patients with moderate to severe 

COPD. 

The potential role of TNF-blocking therapy in the development of malignancies is not 

known. Rates in clinical trial for Remicade cannot be compared to rates in clinical 

trials of other TNF-blockers and may not predict rates observed in a broader patient 

population. Caution should be exercised in considering Remicade treatment in patients 

with a history of malignancy or in continuing treatment in patients who develop 

malignancy while receiving Remicade. 

V. DOSING 1 

Rheumatoid Arthritis 

Induction: 3 mg/kg given IV at 0, 2 and 6 weeks 

Maintenance: 3mg/kg IV every 8 weeks 

Remicade should be given in combination with 

methotrexate. 

For patients who have an incomplete response, doses up 

to 10 mg/kg OR treating as often as every 4 weeks may 

be given, bearing in mind that risk of serious infections 

is increased at higher doses. Monitor for risk of serious 

infections at higher doses. 

Crohn’s Disease (Adult) or 

Crohn’s disease 

Induction: 5mg/kg IV infusion at 0, 2 and Fistulizing 

6 weeks 

Maintenance: 5mgk/kg IV every 8 weeks for moderate 

to severe active Crohn’s disease or Fistulizing Crohn’s 

Disease 

For adult patients who respond and then lose their 

response, doses up to 10mg/kg may be given. 

Patients who do not respond by week 14 are unlikely to 

respond with continued dosing and should discontinue 

Remicade. 

Crohn’s Disease (Pediatric) 

Ankylosing Spondylitis 

Psoriatic Arthritis 

Induction: 5 mg/kg IV infusion at 0, 2 and 6 weeks 

Maintenance: 5 mg/kg IV infusion every 8 weeks. 

Induction: 5 mg/kg IV infusion at 0, 2, and 6 weeks 

Maintenance: 5m/kg IV every 6 weeks 

Induction: 5 mg/kg given IV infusion at 0, 2 and 6 weeks 

Maintenance: 5 mg/kg IV every 8 weeks

Remicade can be used with or without methotrexate. 

Plaque Psoriasis 

Ulcerative Colitis 

Induction: 5 mg/kg IV infusion at 0, 2, and 6 weeks 

Maintenance: 5m/kg IV every 8 weeks 

Induction: 5 mg/kg IV infusion at 0, 2 and 6 weeks 

Maintenance: 5 mg/kg IV every 8 weeks for moderate to 

severe active ulcerative colitis 

VI. 

AVAILABILITY 

Remicade lyophilized concentrate for IV injection is available as 100 mg per 20 mL vial 

supplied in individually boxed single-use vials. 1 

VII. 

BACKGROUND 

A. Description 

Remicade is a chimeric IgG1κ monoclonal antibody, which binds specifically to human 

TNF-alpha and inhibits binding of TNF-alpha to its receptors. 1 

B. Clinical Studies 

1. Ankylosing Spondylitis (AS) 

A randomized, double-blind, multicenter, placebo-controlled study, the Ankylosing 

Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) 

18 , was conducted in 279 patients with active ankylosing spondylitis refractory to 

conventional therapy. The primary end point was the proportion of patients with a 

20% improvement (ASAS20 responders) at week 24. Patients were randomized to 

receive 5 mg/kg of Remicade (n = 201) or placebo (n = 78) at weeks 0, 2, 6, 12, and 

18. After 24 weeks, 61.2% of patients in the Remicade group achieved ASAS20 

compared with 19.2% of the placebo group (p < 0.001). Adverse events were reported 

by 82.2% of the Remicade group and 72% of the placebo group. Most adverse events 

were mild to moderate in severity. 

A 3-year extension study of the original 12-week study evaluated the long-term 

efficacy in 43 patients who had received open-label infusions of infliximab 5 mg/kg 

every 6 weeks beginning with the week-108 infusion. 19 Over the three years of the 

study, the BASDAI 50 % response was consistent. Compared with baseline, a 

reduction of at least 50 % in the BASDAI score was achieved in 63 %, 58 %, and 61 

% of Remicade treated patients at week 56, 102, and 156, respectively. Long-term 

treatment of Remicade was well tolerated. 

2. Crohn’s Disease 

a. Adult Crohn’s disease 

In a multi-center, randomized international trial, the efficacy of infliximab was 

evaluated in 545 patients with moderately to severely active CD who failed 

conventional therapies (e.g. 5-aminosalicylates, immunomodulators, steroids). 7 At 

baseline, the median Crohn's Disease Activity Index (CDAI) score was 295. All 

patients received an initial infusion of 5 mg/kg at Week 0. At Week 2, patients

were randomized based on clinical response, defined as a reduction in CDAI ≥ 

25% and ≥ 70 points, to one of the following maintenance treatment groups: Group 

I: Placebo at Weeks 2, 6, and then placebo every 8 weeks; Group II: Remicade 5 

mg/kg at Weeks 2, 6 and then 5 mg/kg every 8 weeks; Group III: Remicade 5 

mg/kg at Weeks 2, 6 and then 10 mg/kg every 8 weeks. Only the Week 2 

responders were analyzed for the primary endpoints of the trial. The 2 co-primary 

endpoints were the proportion of patients in remission (CDAI 40 weeks vs. 14 weeks, p < 0.001). At 54 weeks, 36% of the

patients in the Remicade group maintained fistula closure compared with 19 % of the 

patient in the placebo group. Serious infections occurred in 5% of all randomized 

patients. 

A randomized, multicenter, double-blinded, placebo-controlled trial of Remicade was 

conducted in 94 adult patients who had draining abdominal or perianal fistulas for at least 

three months. 9 Patients were randomized to one of the three arms: placebo, Remicade 5 

mg/kg or Remicade 10 mg/kg at weeks 0, 2, and 6. After two or three infusions, 68 % of 

patients who received Remicade 5 mg/kg and 56 % of those who received Remicade 10 

mg/kg achieved at least 50 % reduction in the number of draining fistulas from baseline, 

compared with 26 % of the patients in the placebo group (p = 0.002 and p = 0.02, 

respectively). More than 60% of patients in all groups had adverse events. The most 

common adverse events reported in the Remicade-treated patients were headache, 

abscess, upper respiratory tract infection, and fatigue. 

4. Psoriatic Arthritis (PsA) 

A phase III, double-blind, placebo-controlled, randomized, parallel group study, the 

IMPACT 2 trial, evaulated the efficacy of Remicade in adult patients with active PsA 

unresponsive to previous treatment. 14 A total of 200 patients received either placebo or 

Remicade 5 mg/kg at weeks 0, 2, and 6 followed by maintenance dosing at weeks 14 and 

22. Patients in the placebo group with < 10% improvement from baseline in both swollen 

and tender joint counts received Remicade 5 mg/kg at weeks 16, 18, and 22. The primary 

end point was to measure the proportion of patients achieving an ACR20 response at 

week 14. Fifty-eight percent (58 %) of patients receiving Remicade and 11% of those 

receiving placebo achieved an ACR20 response at week 14 (p

HAQ scores averaged over weeks 30-54. The patients receiving MTX-3 mg/kg Remicade 

and MTX-6 mg/kg Remicade achieved a significantly higher median percentage of ACR- 

N (inter-quartile range [IQR]) (38.9% [0.0, 77.3] and 46.7% [0.0, 82.1], respectively) 

than those in the MTX-placebo group (26.4% [0.0, 64.3]) (p2) despite conventional therapy. In the first study (ACT I), patients receives 

Remicade 5mg/kg IV (n=121), 10mg/kg (n=122) or placebo (n= 121) and in ACT II, 364 

patients were randomized to receive Remicade 5mg/kg (n=121), 10mg/kg (n=120) and 

placebo (n=123). Treatments were given at baseline, week 2, 6 and then every 8 weeks 

through week 22 in ACT II and 46 weeks in ACT I. The primary end point was a clinical 

response at week 8. Clinical response was defined as a decrease from baseline in the total 

Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the 

subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 

0 or 1. Clinical remission was defined as a total Mayo score of 2 points or lower, with no 

individual subscore exceeding 1 point. Mucosal healing was defined as absolute subscore 

for endoscopy of 0 or 1. The results were similar in both trials. In ACT I, 69% and 61% 

of patients receiving 5mg/kg and 10mg/kg, respectively, responded within 8 weeks, 

compared with 37% of placebo (p

First update of the international ASAS consensus statement for the use of anti- 

TNF agents in patients with ankylosing spondylitis. 

(1) Diagnosis: Patients normally fulfilling modified New York Criteria for 

definitive ankylosing spondylitis: 

(a) Radiological criterion: Sacroiliitis (> grade II bilaterally or grade III-IV 

unilaterally) 

(b) Clinical criteria (two of the following three): low back pain and stiffness 

for > 3 months that improves with exercise but is not relieved by rest; 

limitation of motion of the lumbar spine in both the sagittal and frontal 

planes or limitation of chest expansion relative to normal values 

correlated for age and sex 

(2) Disease activity: Active disease for > 4 weeks, and BASDAI > 4 (on a scale 

of 0-10). The BASDAI and the expert opinion should be recorded at two 

different times about one month apart. 

(3) Failure of standard treatment: All patients must have had adequate trials of at 

least two NSAIDs. An adequate therapeutic trial is defined as: 

(a) Treatment for > 3 months at maximal recommended or tolerated antiinflammatory 

dose unless contraindicated 

(b) Treatment for < 3 months where treatment was withdrawn because of 

intolerance, toxicity, or contraindications. 

(c) Patients with symptomatic peripheral arthritis must have had adequate 

therapeutic trial of both NSAIDs and sulfasalazine 

(d) Patients with symptomatic enthesitis must have had an adequate 

therapeutically trial local steroid injections unless contraindicated 

(4) Assessment of response: 

(a) Responder criteria: A 50% relative change or absolute change of 2 (scale 

of 0-10) and expert opinion 

(b) Time of evaluation: between 6 and 12 weeks 

b. British Society for Rheumatology (BSR) Guideline for Prescribing TNFα 

Blockers in Adults with Ankylosing Spondylitis (2004) 12 

Treatment guideline for use of TNF blocking agents includes: 

(1) A definite diagnosis of ankylosing spondylitis as defined by the modified 

New York criteria 

(2) Evidence of active disease as defined by BASDAI ≥ 4 and spinal pain VAS ≥ 

4, both of which are recorded on two occasions at least four weeks apart 

without any change of treatment 

(3) Criteria for withdrawal of therapy: Development of severe adverse effects, or 

inefficacy as indicated by failure to improve BASDAI score by 50% or to fall 

by ≥ 2 units, and/or for the spinal pain VAS to reduce by ≥ 2 units after 3 

months of therapy. 

(4) Response to treatment is defined as: Reduction of BASDAI to 50% of the 

pretreatment value or a fall of ≥ 2 units and reduction of the spinal pain VAS 

by ≥ 2 units. 

(5) Response to therapy should be accessed between 6 and 12 weeks after 

initiation of treatment. If the response criteria are not met, a second 

assessment should be made at 12 weeks. Treatment should not be stopped 

because of ineffectiveness within 12 weeks. 

(6) Failure to maintain the original response leads to repeat assessment after 6 

weeks; failure to maintain response on both occasions leads to cessation or 

change of treatment.

2. Crohn's Disease 

a. American College of Gastroenterology: Management of Crohn's Disease in 

Adults (2001) 22 

(1) For moderate-to-severe disease: Remicade is an effective adjunct and maybe 

be an alternative to steroid therapy in selected patients in whom 

corticosteroids are contraindicated or ineffective (Note: patients with 

moderate-to-severe disease are treated with prednisone 40-60 mg daily). 

(2) Infliximab is also effective in patients who have not responded to 

aminosalicylates, antibiotics, corticosteroids, or immunomodulators. 

Retreatment is likely to be necessary on an ongoing basis to prevent relapse. 

(3) Severe disease: There are no data on the use of Remicade for treatment of 

severe Crohn's disease. 

(4) Perianal disease: Non-supportive, chronic fistulization or perianal fissuring is 

treated medically with antibiotics, immunosuppressives, or Remicade. 

3. Psoriatic Arthritis 

British Society for Rheumatology Standards Guidelines Audit Working Group 

(SGAWA): Guideline for anti-TNF-α therapy in psoriatic arthritis (2004) 13 

The anti-TNF-α therapy is recommended for patients with active psoriatic arthritis 

who had failed an adequate trial of at least two of the standard DMARDs individually 

or in combination. An adequate therapeutic trial is defined as: 

- Treatment for at least 6 months, of which least 2 months is at standard target 

dose (unless significant intolerance or toxicity limits the dose). 

- Treatment for < 6 months, where treatment is withdrawn because of drug 

intolerance or toxicity. 

- When treatment is withdrawn because of intolerance or toxicity after >2 

months therapy, at least 2 months should have been at therapeutic doses. 

4. Rheumatoid Arthritis 

a. American College of Rheumatology (ACR) (2002) 2 

All patients with RA are candidates for DMARD therapy. Although NSAIDs and 

glucocorticoids may alleviate symptoms, joint damage may continue to occur and 

progress. DMARDs have the potential to reduce or prevent joint damage, 

preserve joint integrity and function, and ultimately, reduce the total costs of 

health care and maintain economic productivity of the patient with RA. The 

initiation of DMARDs should not be delayed beyond 3 months for any patient 

with established diagnosis who, despite adequate treatment with NSAIDs, has 

ongoing joint pain, significant morning stiffness or fatigue, active synovitis, 

persistent elevations of ESR or CRP level or radiographic joint damage. For any 

untreated patients with persistent synovitis and joint damage, DMARD treatment 

should be started promptly to prevent or slow further damage. DMARDs 

commonly used in RA include hydroxychloroquine, sulfasalazine, methotrexate, 

leflunomide, etanercept and Remicade. Less frequently used DMARDs are 

azathioprine, penicillamine, gold salts, minocycline, and cyclosporine. 

Based on considerations of safety, convenience, and cost, most rheumatologists 

select hydroxychloroquine or sulfasalazine first. For patients with very active 

disease or with indicators of a poorer prognosis, MTX or combination therapy is

preferred. The ACR Subcommittee recommends a trial of methotrexate as 

monotherapy or as a component of combination therapy in patients whose 

treatment has not yet included methotrexate. Many rheumatologist select MTX as 

the initial DMARD because of its favorable efficacy and toxicity profile, low cost 

and established track record in the treatment of RA. MTX has become the 

standard by which new DMARDs are evaluated. Randomized clinical trials have 

established efficacy in RA, particularly in patients with severe disease. 

Longitudinal studies and randomized controlled trials show that MTX retards the 

progression of radiographic erosions. For patients in whom methotrexate is 

contraindicated or has failed to achieve satisfactory disease control either because 

of lack of efficacy (in doses up to 25 mg/week) or intolerance, treatment with 

biologic agents or DMARDs, either alone or in combination, is recommended. 

The ACR recommends assessment of tuberculosis risk prior to initiation of a 

TNF-alpha antagonist due to postmarketing surveillance which yielded reports of 

sepsis, tuberculosis, atypical mycobacterial infections, fungal infections, 

opportunistic infections, demyelinating disorders and aplastic anemia. 

b. International Consensus Statement on Biological Agents for Treatment of 

Rheumatic Diseases (2004) 5 

Tumor necrosis factor (TNF) blockers have shown effective for the treatment of 

rheumatoid arthritis in methotrexate naïve patients (category A, D evidence); 

however, the use of TNF blocking agents as the first DMARD for the treatment 

of rheumatoid arthritis should, at present, be limited in considering emerging data 

on long-term safety, effectiveness, and economic factor. TNF blocking agents 

may be considered as the initial DMARD in some patients (category A, D 

evidence). 

When used in adequate doses and sufficiently frequent dosing regimens, TNF 

blocking agents should lead to significant, documented improvement within 12 

weeks for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and 

juvenile rheumatoid arthritis (category A evidence). If documentable significant 

improvement occurs, treatment should be continued. If patients show no response 

to TNF blocking agents at their maximum approved dose, treatment should be 

discontinued in 12 weeks. If an incomplete response occurs, increasing the dose 

or reducing the dosing interval may provide additional benefits in rheumatoid 

arthritis (category B evidence). 

Categories of Evidence: 

Category A evidence: based on evidence from at least one randomized controlled 

trial or on the meta-analyses of randomized controlled trials. 

Category B evidence: based on evidence from at least one controlled trial without 

randomization or at least one other type of experimental study or on extrapolated 

recommendations from randomized controlled trials or meta-analyses. 

Category D evidence: based on expert committee reports or opinions or clinical 

experience or respected authorities, or both, or extrapolated recommendations 

from randomized controlled trials, meta-analyses, non-randomized controlled 

trials, experimental studies, or non-experimental descriptive studies. 

5. Ulcerative Colitis

Ulcerative Colitis Practice Guideline in Adults (Update): American College of 

Gastroenterologist (ACG), Practice Parameters Committee. 16 

Goals of treatment are directed at inducing and maintaining remission of symptoms 

and mucosal healing in order to provide improved quality of life. Once a diagnosis of 

UC is confirmed, the anatomic extent is assessed endoscopically to determine if the 

inflammation is distal or extensive. The severity and extent of the disease is based on 

clinical and endoscopic findings. Severity is defined as mild, moderate, severe or 

fulminant. Patients with mild disease have less than 4 stools daily and a normal ESR. 

Moderate disease is characterized by more than 4 stools per day with minimal signs 

of toxicity. Severe disease is characterized by more than 6 bloody stools daily and 

evidence of toxicity as demonstrated by fever, tachycardia, anemia or an elevated 

ESR. Patients with fulminant disease have more than 10 bowel movements daily, 

continuous bleeding, toxicity, abdominal tenderness and distention, blood transfusion 

requirement and colonic dilation on abdominal plain film. 

The ACG recommends the following for patients with UC: 

(1) Distal UC may be treated with oral aminosalicylates, topical mesalamine or 

topical steroids (Evidence A). Oral therapy with aminosalicylates, sulfasalazine, 

olsalazine, mesalamine or balsalazide is beneficial in achieving and maintaining 

remission. Mesalamine suppositories are effective in the maintenance of 

remission in patients with proctitis, while mesalamine enemas are effective in 

patients with distal colitis (Evidence A). 

(2) Extensive active UC should begin with oral sulfasalazine up to 4-6 g per day or 

alternate aminosalicylates up to 4.8 g per day (Evidence A). The newer 

aminosalicylates (balsalazide, olsalazine, etc.) are all superior to placebo and 

equivalent to sulfasalazine in acute therapy. Oral prednisone demonstrates a dose 

response effect between 20 and 60 mg per day, with moderately more effect at 

higher doses. Azathioprine or 6-mercaptopurine may be useful as steroid-sparing 

agents for steroid-dependent patients and for maintenance of remission not 

adequately sustained by aminosalicylates, and occasionally for patients who are 

steroid-refractory but not acutely ill (Evidence C). 

(3) For severe UC refractory to maximal oral treatment with prednisone, 

aminosalicylates, topical medications, or who present with toxicity should be 

hospitalized for a course of IV steroids (Evidence C). Failure to demonstrate 

significant improvement within 7-10 days is an indication for colectomy 

(Evidence C) or IV cyclosporine (Evidence A). 

Categories of Evidence: 

Grade A evidence: based on multiple well-designed randomized (therapeutic) or 

cohort (descriptive) controlled trials, each involving a number of participants to be 

sufficient statistical power. 

Grade B evidence: based on at least one large well-designed clinical trial with or 

without randomization, from cohort or case-control analytical studies, or welldesigned 

meta-analysis. 

Grade C evidence: based on clinical experience, descriptive studies, or reports of 

expert committees. 

VIII. DEFINITIONS 

A. American College of Rheumatology (ACR) response criteria 2

1. The ACR20 response criterion is defined as a 20 % improvement in swollen and 

tender joint count and 20 % improvement in three of the outcome measures listed 

below: 

(a) Physician's global assessment 

(b) Patient's global assessment 

(c) Pain 

(d) Functional status or physical disability 

(e) Acute phase reactant (erythrocyte sedimentation rate or C-reactive protein) 

2. The ACR50 and 70 responses are defined as a 50 % and a 70 % response, 

respectively, in the aforementioned criteria. 

B. Crohn's Disease Activity Index (CDAI) 9 

The CDAI is the most widely accepted assessment of clinical activity of Crohn's Disease. 

The scores can range from 0 to about 600, with higher scores indicating more severe 

disease. Clinically inactive disease, or remission, is defined by a score of ≤ 150 points 

and severe active disease is defined as a score of ≥ 450 points. 

C. Radiographic grading system in ankylosing spondylitis 12 

1. Grade II: evidence or erosion and sclerosis 

2. Grade III: erosion sclerosis and early ankylosis 

3. Grade IV: total ankylosis 

D. Criteria of Disease Severity in Ulcerative Colitis 16 

1. Mild disease has less than 4 stools daily and a normal ESR. 

2. Moderate disease is characterized by more than 4 stools per day with minimal signs of 

toxicity 

3. Severe disease is characterized by more than 6 bloody stools daily and evidence of 

toxicity as demonstrated by fever, tachycardia, anemia or an elevated ESR. 

4. Fulminant disease has more than 10 bowel movement daily, continuous bleeding, 

toxicity, abdominal tenderness and distention, blood transfusion requirement and 

colonic dilation on abdominal plain film. 

IX. 

REFERENCES 

1. Remicade Prescribing Information. Centocor, Inc., October 2006. 

2. American College of Rheumatology (ACR) Subcommittee on Rheumatoid Arthritis 

Guidelines. Guidelines for the Management of Rheumatoid Arthritis 2002 Update. 

Arthritis Rheum 2002; 46(2):328-346. 

3. Maini R, St Clair WE, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis 

factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving 

concomitant methotrexate: a randomized phase III trial. Lancet 1999;354:1932-39. 

4. Pavy S. Constantin A, Pham T, et al. Methotrexate therapy for rheumatoid arthritis: 

clinical practice guidelines based on published evidence and expert opinions. Joint Bone 

Spine 2006; 1-8. 

5. Furst DE, Breedveld FC, Kadlden JR, et al. Updated consensus statement on biological 

agents, specifically tumour necrosis factor α (TNF α) blocking agents and interleukin-1 

receptor antagonist (IL-1ra), for the treatment of rheumatic diseases. Ann Rheum Dis 

2004; 63(Suppl II):ii2-ii12. 

6. Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology preliminary 

definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38(6):727-735.

7. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's 

disease: the ACCENT I randomized trial. Lancet 2002;359:1541-49. 

8. Targan SR, Hanauer SB, Sander JH, et al. A short-term study of chimeric monoclonal 

antibody cA2 to tumor necrosis factor α for Crohn's disease. N Engl J Med 2005; 

337(15):1029-1035. 

9. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment in patients with 

Crohn's disease. N Engl J Med 1999;340:1398-405. 

10. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for 

fistulizing Crohn's disease. N Engl J Med 2004;350:876-85. 

11. Braun J, Davis J, Dougados M, Sieper J, Linden SVD, Heijde DVD, for the ASAS 

working group. First update of the international ASAS consensus statement for the sue of 

anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis.2006;65:316- 

320. 

12. Keats A, Barkham A, Bhalla K, et al. on the behalf of the BSR Standards, Guidelines and 

Audit Working Group. British Society for Rheumatology (BSR) Guideline for 

prescribing TNFα blockers in adults with ankylosing spondylitis. Report of a working 

party of the British Society of Rheumatology. Rheumatol 2005; 44:939-947. 

13. Kyle S, Chandler D, Griffiths EM, et al. Guideline for anti-TNF-α therapy in psoriatic 

arthritis. Rheumatol 2005; 44:390-397. 

14. Antoni C, Krueger GG, de Vlam K, et al. Infliximab improves signs and symptoms of 

psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005; 64:1150-1157. 

15. Antoni CE, Kavanaugh A, Kirkham B, et al. Sustained benefits of Infliximab therapy or 

dermatologic and articular manifestations of psoriatic arthritis. Results from the 

Infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum 

2005;52(4):1227-1236. 

16. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): 

American College of Gastroenterology, Practice Parameter Committee. Am J 

Gastroenterol 2004; 99(7):1371-85. 

17. Rutgeers P, Sandborn WJ, Feagan BG, et al. Infliximab for inductions and maintenance 

therapy for ulcerative colitis. NEJM 2005;353(23):2462-76. 

18. Van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in 

patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial 

(ASSERT). Arthritis Rheum 2005;52(2):582-591. 

19. Braun J, Baraliakos X, Brandt J, et al. Persistent clinical response to the anti-TNF-α 

antibody infliximab in patients with ankylosing spondylitis over 3 years. Rheumatology 

2005;44:670-676. 

20. Lipsky PE, van der Heijde D, St. Clair EW, et al. Infliximab and methotrexate in the 

treatment of rheumatoid arthritis. N Engl J Med 2000; 343:1594-602. 

21. St. Clair EW, van der Heijde DMFM, Smolen JS, et al. Combination of infliximab and 

methotrexate therapy for early rheumatoid arthritis, a randomized, controlled trial. 

Arthritis & Rheumatism 2004; 55(11): 3432-3443. 

22. Nanauer SB, Sandborn W, and the Practice Parameters Committee of the American 

College of Gastroenterology. Management of Crohn's disease in adults. Am J 

Gastroenterol 2004;96:635-643. 

23. Reich K, Nestle FO, Papp K et al. Infliximab induction and maintenance therapy for 

moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 

2005;366(9494):1367-74. 

V. ENDNOTES 

a. Preliminary results of the ASPIRE trial 20 , a large controlled investigational study involving 

1049 patients with early rheumatoid arthritis indicated that Remicade plus methotrexate was 

more effective than methotrexate (given up to a 20 mg/week) alone in improving the signs 

and symptoms of RA and preventing radiographic joint damage.

Methotrexate is used by most rheumatologists as the first line disease-modifying 

antirheumatic drug for patients with rheumatoid arthritis (RA). This choice rests on the good 

effectiveness and safety profile of the drug, its low cost, and the availability of long-term 

follow-up data on RA patients given methotrexate. In addition, recent data indicate that 

methotrexate can produce substantial survival benefits by reducing cardiovascular mortality 

in patients with RA. 4 

The recommended starting dosage for MTX in patients with RA should not be less than 10 

mg/week and increase at 6 weeks interval to a maximum of 20 mg/week based on disease 

severity, patient related factors, and tolerance. 4 

b. In the Remicade clinical study, moderate to severely active Crohn’s disease was defined 

as a Crohn's Disease Activity Index (CDAI), ≥220 and ≤400, inclusive. 1 

c. Remicade has not been studied in children with Crohn’s disease < 6 years of age. Long 

term (greater than one year) safety and efficacy of Remicade in pediatric Crohn’s disease 

patients have not been established in clinical trials. 1 

d. Efficacy and safety of Remicade treatment beyond 50 weeks have not been evaluated in 

patients with plaque psoriasis. 

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