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

ObjectivesTo 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.MethodsPatients 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.ResultsA 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.ConclusionsPatients 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.

Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints

“…Conversely, 51.1% of the patients in the Infliximab as First-Line Therapy in Patients With Early Active Axial Spondyloarthritis Trial (INFAST) had a BASDAI50 response at week 28 after receiving a maximal dose of naproxen 1,000 mg daily. Consistent with the results of the present study, the mean BASDAI score reached 4.2, a decrease of 33%, at week 6 in these NSAID-treated patients (21). In the latter study, BASDAI50 response was not reported at earlier time points, rendering a head-to-head comparison difficult.…”

Challenges and Advances in Targeting Remission in Axial Spondyloarthritis

“…Although a validated definition of clinical remission or LDA for BASDAI is currently unavailable 23 , certain cutoffs have been used in clinical trials and observational studies (BASDAI < 4 24 ; < 3 or ≤ 3) 25,26,27 . For example, in the INFAST study, 76% of patients with early axSpA receiving infliximab plus naproxen achieved a BASDAI < 3 at Week 28 9 . ASDAS offers a more objective assessment of disease activity because it includes C-reactive protein (CRP), which is a marker of inflammation, and may predict structural progression 28 .…”

“…In 2001, the Assessment of Spondyloarthritis international Society (ASAS) developed a preliminary definition of clinical remission-ASAS partial remission (ASAS PR), which includes assessment of 4 domains: patient global, spinal pain, physical function, and "inflammation" (a proxy for true inflammation, based on morning stiffness) 5 . In clinical trials, 12-15% 5,6 of patients with ankylosing spondylitis (AS) receiving nonsteroidal antiinflammatory drugs (NSAID) achieve partial remission; a ceiling of ~15-40% at 6 months also exists with biologic therapies, including tumor necrosis factor (TNF) inhibitors and secukinumab 7,8 (Table 1 [9][10][11][12][13][14][15][16][17][18][19][20] ). Treating patients with short symptom duration may increase the proportion of patients reaching clinical remission to ~50% 9,21,22 .…”

Biologic agents in immune-mediated inflammatory rheumatic diseases: current state of the art and clinical practice in Romania

“…Numerous other studies have afterwards underlined the efficacy of using Infliximab in AS, not only clinically, but also by the reduction of inflammation visualized using MRI and also functionally, the effects being sustained, over periods exceeding 8 years [11]. Furthermore, Infliximab has been proven to be efficient also in non-radiographic AS, as shown on a subgroup of the patients in the INFAST study [12].…”