t placebo.
Physical function response
Physical function and disability were assessed using the Health Assessment Questionnaire(HAQ-DI) and the general health-related quality of life questionnaire SF-36.
In Study RA I, all doses/schedules of infliximab + MTX showed significantly greaterimprovement from baseline in HAQ-DI and SF-36 physical component summary score
averaged over time through Week 54 compared to placebo + MTX, and no worsening in theSF-36 mental component summary score. The median (interquartile range) improvement
from baseline to Week 54 in HAQ-DI was 0.1 (-0.1, 0.5) for the placebo + MTX group and0.4 (0.1, 0.9) for infliximab + MTX (p<0.001). Both HAQ-DI and SF-36 effects were
maintained through Week 102. Approximately 80% of patients in all doses/schedules ofinfliximab + MTX remained in the trial through 102 weeks.
In Study RA II, both infliximab treatment groups showed greater improvement in HAQ-DIfrom baseline averaged over time through Week 54 compared to MTX alone; 0.7 for
infliximab + MTX vs. 0.6 for MTX alone (P≤0.001). No worsening in the SF-36 mentalcomponent summary score was observed.
14.5 Ankylosing Spondylitis
The safety and efficacy of infliximab were assessed in a randomized, multicenter, doubleblind,placebo-controlled study in 279 patients with active ankylosing spondylitis. Patientswere between 18 and 74 years of age, and had ankylosing spondylitis as defined by themodified New York criteria for Ankylosing Spondylitis.4 Patients were to have had activedisease as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index(BASDAI) score >4 (possible range 0-10) and spinal pain >4 (on a Visual Analog Scale [VAS]of 0-10). Patients with complete ankylosis of the spine were excluded from studyparticipation, and the use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) andsystemic corticosteroids were prohibited. Doses of infliximab 5 mg/kg or placebo wereadministered intravenously at Weeks 0, 2, 6, 12 and 18.
At 24 weeks, improvement in the signs and symptoms of ankylosing spondylitis, as measuredby the proportion of patients achieving a 20% improvement in ASAS response criteria(ASAS 20), was seen in 60% of patients in the infliximab-treated group vs. 18% of patients inthe placebo group (p<0.001). Improvement was observed at Week 2 and maintained throughWeek 24 (Figure 3 and Table 10).
Figure 3 Proportion of patients achieving ASAS 20 response
At 24 weeks, the proportions of patients achieving a 50% and a 70% improvement in thesigns and symptoms of ankylosing spondylitis, as measured by ASAS response criteria
(ASAS 50 and ASAS 70, respectively), were 44% and 28%, respectively, for patientsreceiving infliximab, compared to 9% and 4%, respectively, for patients receiving placebo(P < 0.001, infliximab vs. placebo). A low level of disease activity (defined as a value < 20[on a scale of 0-100 mm] in each of the 4 ASAS response parameters) was achieved in 22%of infliximab-treated patients vs. 1% in placebo-treated patients (P < 0.001).
Table 10 Components of ankylosing spondylitis disease activity
Placebo
(n = 78)
Infliximab 5 mg/kg
(n = 201)
Baseline 24 Weeks Baseline 24 Weeks P-value
ASAS 20 response Criteria
(Mean)
Patient Global Assessmenta 6.6 6.0 6.8 3.8 < 0.001
Spinal paina 7.3 6.5 7.6 4.0 < 0.001
BASFIb 5.8 5.6 5.7 3.6 < 0.001
Inflammationc 6.9 5.8 6.9 3.4 < 0.001
Acute Phase Reactants
Median CRPd (mg/dL) 1.7 1.5 1.5 0.4 < 0.001
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