Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1

Abstract

Objectives: To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs.

Methods: Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance.

Results: A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment.

Conclusions: Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

Trial registration: ClinicalTrials.gov NCT00844805.

Figures

Figure 1

Patient disposition. IFX, infliximab; ITT, intention-to-treat; NPX, naproxen; PBO, placebo.

Figure 2

Percentage of patients who achieved ASAS partial remission (A), ASAS-40 response (B), ASAS-20 response (C), ASDAS major improvement (D), ASDAS clinically important improvement (E) and ASDAS inactive disease (F). p Values are from analysis of treatment group differences in change from baseline at each visit. ASAS, Assessment of SpondyloArthritis international Society; ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; IFX, infliximab; NPX, naproxen; PBO, placebo. aASAS partial remission at week 28 was the primary endpoint of the study. Subjects who withdrew prior to week 28 were not considered to be in partial remission. Patients who were missing more than two ASAS components at week 28 were considered not in partial remission. If a patient had data for at least two ASAS domains at week 28, missing data for the remaining ASAS domains were imputed using a last-observation-carried-forward approach.

Figure 3

Efficacy measures from baseline to week 28: BASDAI (A), BASFI (B), and ASDAS (C). p Values are from analysis of treatment group differences in change from baseline at each visit. ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; IFX, infliximab; NPX, naproxen; PBO, placebo; VAS, visual analogue scale.