The ASPIRE study eva luated responses at 54 weeks in 1,004 methotrexate naive patients with early (3 years disease duration, median 0.6 years) active rheumatoid arthritis (median swollen and tender joint count of 19 and 31, respectively). All patients received methotrexate (optimised to 20 mg/wk by week 8) and either placebo, 3 mg/kg or 6 mg/kg infliximab at weeks 0, 2, and 6 and every 8 weeks thereafter. Results from week 54 are shown in Table 4.
After 54 weeks of treatment, both doses of infliximab + methotrexate resulted in statistically significantly greater improvement in signs and symptoms compared to methotrexate alone as measured by the proportion of patients achieving ACR20, 50 and 70 responses.
In ASPIRE, more than 90% of patients had at least two eva luable X-rays. Reduction in the rate of progression of structural damage was observed at weeks 30 and 54 in the infliximab + methotrexate groups compared to methotrexate alone.
Table 4
Effects on ACRn, Structural Joint Damage and Physical Function at week 54, ASPIRE
Infliximab + MTX
Placebo + MTX
3 mg/kg
6 mg/kg
Combined
Subjects randomised
282
359
363
722
Percentage ACR improvement
Mean ± SDa
24.8 ± 59.7
37.3 ± 52.8
42.0 ± 47.3
39.6 ± 50.1
Change from baseline in total van der Heijde modified Sharp scoreb
Mean ± SDa
3.70 ± 9.61
0.42 ± 5.82
0.51 ± 5.55
0.46 ± 5.68
Median
0.43
0.00
0.00
0.00
Improvement from baseline in HAQ averaged over time from week 30 to week 54c
Mean ± SDd
0.68 ± 0.63
0.80 ± 0.65
0.88 ± 0.65
0.84 ± 0.65
a: p < 0.001, for each infliximab treatment group vs. control
b: greater values indicate more joint damage.
c: HAQ = Health Assessment Questionnaire; greater values indicate less disability.
d: p = 0.030 and < 0.001 for the 3mg/kg and 6mg/kg treatment groups respectively vs. placebo + MTX.
Data to support dose titration in rheumatoid arthritis come from ATTRACT, ASPIRE and the START study. START was a randomised, multicenter, double-blind, 3-arm, parallel-group safety study. In one of the study arms (group 2, n=329), patients with an inadequate response were allowed to dose titrate with 1.5 mg/kg increments from 3 up to 9 mg/kg. The majority (67%) of these patients did not require any dose titration. Of the patients who required a dose titration, 80% achieved clinical response and the majority (64%) of these required only one adjustment of 1.5 mg/kg.
Adult Crohn's disease
Induction treatment in moderately to severely active Crohn's disease
The efficacy of a single dose treatment with infliximab was assessed in 108 patients with active Crohn's disease (Crohn's Disease Activity Index (CDAI) 220 400) in a randomised, double-blinded, placebo-controlled, dose-response study. Of these 108 patients, 27 were treated with the recommended dosage of infliximab 5 mg/kg. All patients had experienced an inadequate response to prior conventional therapies. Concurrent use of stable doses of conventional therapies was permitted, and 92% of patients continued to receive these therapies.
The primary endpoint was the proportion of patients who experi |
