Treatment forGolfer's Toe - Crespine Gel

I ntra -arti Gu lar Hya I u ron i c Aci d
Treatment for Golfer's Toe
Keeping 0lder Golfers on Course
Robert J. Petrella, MD, PhD
Anthony Cogliano, MD
BAGKGR0UilD: Osteoarthritis of the great toe can lead to a pr0gressive decrease in range of motion (R0M) and
pain at the first metatarsophalangeal (MTP) joint. This condition, observed in older golfers, results in reduced
pafticipation and enjoyment of this popular activity.
0BJECTIVE: To assess the efficacy, safety, and patient satisfaction with a series of intra-arlicular injections of
hyaluronic acid (HA) into the first MTP joint in older patients who repofted osteoarthritis-associated pain, loss of
MTP joint ROM, and disability that interfered with golf participation,
METH0DS: Forty-seven consecutive male golfers methe inclusion criteria and were given a weekly intraafticular
HA injection for B weeks. Baseline measures of MTP joint ROM, pain at rest and immediately after tiptoe
walking for 10 m, and global patient satisfaction (GPS)
'16
were c0mpared with measures at 9 and weeks and at
presentation for a second injection series.
RESULTS: Adverse events (only local injection site pain was noted) were

interaction, and nearly unlimited frequency of use.
Whether intra-articular FIA use in a smaller joint, such
as the first MTB provides efficary and a low side-effect
proflle similar to the knee is unknor,r,.n.
Study Design
The protocol and written informed consent for
studies involving human subjects were approved by
the Universityof Westem Ontario ReviewBoard.
The study was a single-center, single-arm, openlabel
trial with an B-week treatment phase. Within 12
months, orthopedic and primary care physicians referred
patients who had pain in the first MTP joint
(unilateral only) and disability (described as reduced
golfing activity without an acute injury event) for at
least 3 months. In addition, all patients had radiogaphic
evidence of osteoarthritis of the first MTP joint
(ie, grade 1 to 3 hallu rigidus using the Regnauld classification
ofjoint-space narrowing and osteophy'te formation).
The subjects provided informed consent, had
not taken NSAIDs for 2 weeks prior to entry, had not
received intra-articular corticosteroid injection in the
first MTP joint within the previous 3 months, did not
have other lower- extremity musculoskeletal disability
or pain, and had pain exceeding 45 Irrn on a 100-mm
visual analogue scale (VAS) immediately following
tiptoe walking for 10 m.
After screening and enrollment, patients completed
assessments and received a 1.0-mL intra-articular
injecton of FIA (Suplasyn, Bioniche Life Sciences Inc,
Belleville, Ontario; 20 mgl2 mL) in the first MTP joint.
An experienced physician delivered the injections
using a27-gauge needle. The toe was semiflexed and
held in gentle traction without topical or local anesthesia
during injection. One dose was administered each
week (t 2 days) for B consecutive weeks in an unblinded
fashion. Patients returned at 9 and 16 weeks and then
self-selected a follow-up visit when theywould request
a second series of injections based on retum of s1'rnptoms
that interfered with their golf activity.
Assessments
Clinical assessments were performed prior to injection
at baseline, at each of seven subsequent weekly
treatment visits, at 16 weeks, and at the second series
visit (28 to 76 weeks after the eighth injection). Adverse
events were recorded at each srudv visit and classified
using standard World Health O rgarrizatio n terminolo gy
and coding. The primary efficacy measures rvere fust
MTP joint pain after 5 minutes of seated rest and following
completion of 10 m of tiptoe rvalking (assessed
byVAS), range of plantar flexion and dorsiflexion of the
first MTP joint (measured from the metatarsal to the
proximal phalanx with a goniometer), and global
patient satisfaction (GPS)(measured on a S-point categorical
scale, with I representing completeh'unsatisfied
and 5 completely satisfied).
In addition to FIA injection therapv patients were
permitted to use standard nonpharmacologic therapies,
including rest, ice, compression, and elevation,
(RICE) and orthoses, aspirin for cardiovascular disease
prophylaxis up to 325 mg/day, and general analgesia
using acetaminophen up to 1 g/dart NSAIDs were not
allowed during HA treatment but were allowed at
patient discretion during the follow-up posttreatment.
Use of altemate treatment modalities was recorded at
16 weeks and at follow-up visits.
Statistical Analysis
Changes in pain scores were evaluated using analysis
of variance (ANOVA) for repeated measures. GPS
was evaluated to determine the proportion of treatment
responders at each treatment and at follow-up
visits. Frequenry of adverse events over the treatment
period and during follow-up were also recorded. level
of statistical significance was accepted at P

Assessmenl
Age (years)
Male
BMI (kg/m2)
Duration of MTP pain (days)
Used NSAID prior to enrollment
Used NSAID in follow-up
Referrals Screened
(n = 56)
70.5 t 3.1
56 (100%)
27 .1 x 1.4
189.B t23.2
31
Data not collected
Enrolled
(n = 47)
71 t 4.3
47 (100"/,)
26.3 t 1.7
142.6 t28.7
30
6
Severity of pain immediately after walking 10 m on tiptoe (measured on a 100-mm visual analog scale)
Moderate (> 60 mm) 67Yo 66%
Mild (45-60 mm) 32Yo 34Yo
< Mild (< 45 mm) 1o/o \Yo
Osleoarthritis assessment by Regnauld classification
Grade 1 41Yo
Grade 2 40%
Grade 3 19%
Used nonpharmacologic therapies during study (eg, RICE, orlhoses)
Data not collected
36%
42o/o
22o/o
2
BMI = body mass index; MTP = first metatarsophalangealyoint; NSAID = nonsteroidalanti-inflammatory drug; RICE= rest, ice, compression.
and elevation
Results
Fifty-six patients were referred over the study period,
and 47 subjects met entry criteria and provided informed
consent. AII 47 patients completed each
treatment session and reported for follow-up assessments.
All subjects were men, with mean age of 7l (t
4.3) years and a mean body mass index of 26.3 (t 1.7)
kglm2. Osteoarthritis of the fust MTP joint was found
in 37 patients on the right foot and in 11 patients on
the left foot. One patient had bilateral osteoarthritis,
but data from only the left foot were used in the study;
osteoarthritis in the right foot was found incidentally
at the end of the study. Radiographs of the first MTP
joint showed36To had grade l,42Vo had grade 2, and
22To had grade 3 osteoarthritis (Regnauld classification).
Baseline demographic characteristics and additional
therapies used over the treatment phase and
during follow-up were recorded (table l). No significant
difference was observed from prestudy and follow-up
levels of the use of or[hoses, acetaminophen,
orNSAIDs.
E
g
70
6n
LTJ
U)
+
yp30
'6
o-
10
HA Treatment
0 Baseline g weeks '16 weeks Follow-up
. P

Rest pain (mm).
Tiptoe-walking pain (mm).
Range of motion (degrees)
Increase from baseline
Global patient satisfaction (S-point scale)
Adverse events, pain only
(number of patients)
N/A
Baseline
(n = 47)
41 .2 x 3.1Ï
68.9 t 5.9
6.3 t 4.1
3.1 t 1.3
9Wk
(n = 47)
29.4 t 3.3Ï
40.2 x 4.1+
26.3 t 10.51
16"
4.86 t 0.2
2
16 Wk
(n = 47)
30.4 r 2.9ï
32.8 t 3.1r
32.6 x97t
22"
4.51 t 0,3
0
Follow-up
(n = 47)
26.1 x2.61
59.0 t 18.4S
28.7 t7.51
19"
4.6 t 0.1311
0
.Measured
on a 100-mm visual analoo scale.
ï P

activi$ in addition to standard pain and disability
assessment. " Viscosupplementation with intra- articu -
lar FIA appears to extend pain relief beyond the product's
biological kinetics.'o The structure-modifying
effects (eg, improved chondrocyte density, reduced
synovial inflammation, increased slmovial repair process)
in the osteoarthritic joint may relate to pain
relief,''rz'ts and this is an area of active investigation.
lVhile the evidence regarding viscosupplementation
with FIA in the knee continues to evolve,'limited evidence
and experience existwith other joints, and none,
to ou-r hlowledge, is lcror,rrn in small articular joints. In
two limited studies6''6 in patients who had painful
shoulders, intra-articular FIA injection improved pain
and fr.rnction; therefore, similar efficary in other articular
joints requires ongoing investigation.
Limitations. The present study had several limitations
that could affect the general applicability of the
results. This unblinded, open-label, unrandomized
trial had no active comparator €unong a small number
of otherwise healthy subjects. Future studies should
include larger subject numbers to achieve appropriate
statistical power and use a randomized design that
would include an active comparator treatment arm to
further address efficary and safety.
We used a 1.0-mL HA intra-articular injection administered
once weekly over B consecutive weeks. This
was based on the clinical experience of the primary
investigator with differing volumes and treatment
schedules in this population and was in accordance
with previous weekly treatment schedules for HA in
the knee. Formal dose-response studies would determine
the optimal treatment course for osteoarthritis of
the first MTP joint.
Gonclusions and Recommendations
HA injection produced a significant, long-term
improvement in pain and function in older patients
who had osteoarthritis of the fust MTP joint. Because
of the small articular space, we used 1.0 mL of HA
without any associated local and systemic adverse
events. The regimen used in this study produced high
patient satisfaction, was associated with limited need
for concomitant therapies during follow-up, and
appeared acceptable as a repeated, long-term therapeutic
option. PSM
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2oNo.7.July2004