ek 8 74% 86% 80%
Week 30 65% 74% 71%
Week 54 62% 69% 67%
Physician’s Global Assessment
Baseline 4% 6% 3%
Week 8 44% 74% 64%
Week 30 36% 57% 55%
Week 54 26% 53% 53%
Endoscopy findings
Baseline 0% 0% 0%
Week 8 34% 62% 59%
Week 30 26% 51% 52%
Week 54 21% 50% 51%
14.4 Rheumatoid Arthritis
The safety and efficacy of infliximab were assessed in 2 multicenter, randomized, doubleblind,pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use ofstable doses of folic acid, oral corticosteroids (≤ 10 mg/day) and/or non-steroidal antiinflammatorydrugs (NSAIDs) was permitted.
Study RA I was a placebo-controlled study of 428 patients with active rheumatoid arthritisdespite treatment with MTX. Patients enrolled had a median age of 54 years, median diseaseduration of 8.4 years, median swollen and tender joint count of 20 and 31 respectively, andwere on a median dose of 15 mg/wk of MTX. Patients received either placebo + MTX or oneof 4 doses/schedules of infliximab + MTX: 3 mg/kg or 10 mg/kg of infliximab by IV infusionat Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination withMTX.
Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naivepatients of 3 or fewer years’ duration active rheumatoid arthritis. Patients enrolled had amedian age of 51 years with a median disease duration of 0.6 years, median swollen andtender joint count of 19 and 31, respectively, and >80% of patients had baseline joint erosions.
At randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and eitherplacebo, 3 mg/kg or 6 mg/kg infliximab at Weeks 0, 2, and 6 and every 8 weeks thereafter.
Data on use of infliximab without concurrent MTX are limited [see Adverse Reactions (6.1)].
Clinical responseIn Study RA I, all doses/schedules of infliximab + MTX resulted in improvement in signs andsymptoms as measured by the American College of Rheumatology response criteria (ACR 20)with a higher percentage of patients achieving an ACR 20, 50 and 70 compared to placebo +MTX (Table 7). This improvement was observed at Week 2 and maintained through Week102. Greater effects on each component of the ACR 20 were observed in all patients treatedwith infliximab + MTX compared to placebo + MTX (Table 8). More patients treated withinfliximab reached a major clinical response than placebo-treated patients (Table 7).
In Study RA II, after 54 weeks of treatment, both doses of infliximab + MTX resulted instatistically significantly greater response in signs and symptoms compared to MTX alone asmeasured by the proportion of patients achieving ACR 20, 50 and 70 responses (Table 7).
More patients treated with infliximab reached a major clinical response than placebo-treatedpatients (Table 7).
Table 7 ACR response (percent of patients)
Study RA I Study RA II
Infliximab + MTX Infliximab + MTX
3 mg/kg 10 mg/kg 3 mg/kg 6 mg/kg
Response Placebo
+ MTX q8 wks q4 wks q8 wks q4 wks Placebo
+ MTX q8 wks q8 wks
(n = 88) (n = 86) (n = 86) (n = 87) (n = 81) (n = 274) (n = 351) (n = 355)
ACR20
Week 30 20% 50%a 50%a 52%a 58%a N/A N/A N/A
Week 54 17% 42%a 48%a 59%a 59%a 54% 62%c 66%a
ACR50
Week 30 5% 27%a 29%a 31%a 26%a N/A N/A N/A
Week 54 9% 21%c 34%a 40%a 38%a 32% 46%a 50%a
ACR70
Week 30 0% 8%b 11%b 18%a 11%a N/A N/A N/A
Week 54 2% 11%c 18%a 26%a 19%a 21% 33%b 37% a
Major clinical
response# 0% 7% 8%b 15%a 6%c 8% 12% 17%a
# A major clinical response was defined as a 70% ACR response for 6 consecutive months (consecutive visits spanning at lea |
