A post-hoc analysis of data from the Infliximab as First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) showed that a combination of naproxen (NPX) and the anti-tumor necrosis factor (TNF)-α inhibitor infliximab (IFX) was more effective at inducing partial remission in patients with ankylosing spondylitis (AS) than in those with nonradiographic axial spondyloarthritis (nr-axSpA). The data were in contrast with previous studies that suggested anti-TNF-α inhibitors were similarly effective in both disease states. The analysis was led by Dr Joachim Sieper of Charité – Medical University of Berlin, and was published in Rheumatology.1
INFAST sought to determine whether the combination of IFX and a nonsteroidal anti-inflammatory drug (NSAID) was superior to an NSAID alone in patients with moderate-to-severe active axial spondyloarthritis (axSpA) with a symptom duration of ˂3 years. It was the first trial to investigate the efficacy of TNF-α antagonist therapy in patients with active axSpA not refractory to NSAIDs.
Both patients with AS and nr-axSpA were included, but the original published findings did not report their results separately. Results of that study demonstrated that patients who received both NPX and IFX were more likely to reach Assessment of Spondyloarthritis International Society (ASAS) partial remission than patients who received NSAID monotherapy (61.9% vs 35.3%, respectively).2
The analysis in the recently published study included 150 patients, 94 who were classified as having AS and 56 as having nr-axSpA. At week 28, the pre-determined time frame, 70.5% of the patients with AS who received IFX plus NPX achieved ASAS partial remission, a measure that was met by only 33.3% of those who received NPX monotherapy. Among patients with nr-axSpA, 50.0% of those receiving infliximab and naproxen reached ASAS partial remission at 28 weeks vs. 37.5% of patients on naproxen alone, a finding that was not statistically significant.1
In an email interview, Atul Deodhar, MD, MRCP, of the Oregon Health and Science University School of Medicine, told Rheumatology Advisor that the study’s results are unlikely to alter the treatment paradigm for axSpA. “I do not think that this study will change how we manage axial spondyloarthritis since patients in daily clinical practice do not resemble patients participating in this trial. Patients admitted in this trial were unique: they had not failed NSAIDs before starting biologic treatment — this never happens in daily practice — and patients had a very short disease duration.”
Summary & Clinical Applicability
“Patients with early axSpA had better outcomes when treated with IFX + NPX than NPX alone, but also showed good outcomes when receiving NPX alone,” concluded the investigators. “Other predictors of partial remission were HLA-B27 positivity and young age. Objective signs of inflammation, such as CRP and MRI inflammation, were less predictive in this early axSpA cohort. Thus early diagnosis seems to be important to achieve a good treatment effect, including in patients who already fulfil the modified New York [radiographic] criteria for AS.”
- The authors acknowledged the “population in INFAST was unique in that patients had not failed NSAIDs before starting biologic treatment and patients had a short mean disease duration (≤2 years).
- Analysis of the AS study population was not planned in the original study and therefore it is not powered for the analysis of subgroups of patients. The authors note that “inferences about the differences between the two subsets of the populations should be made with caution.”
Dr Rudwaleit is a consultant and member of the speakers bureau for Abbott, BMS, MSD, Pfizer, UCB and is a member of the speakers bureau for Roche. Dr Huyck is an employee of Merck Sharp & Dohme. Dr Vastesaeger is an employee of MSD Belgium. Dr Wollenhaupt is a member of the speakers bureau and a consultant for AbbVie, Bristol-Myers-Squibb, MSD, Pfizer and UCB. Dr Chitkara, at the time of manuscript preparation and submission, was a full-time employee of Merck & Co. Dr Yao is an employee of Merck Sharp & Dohme. Dr Govoni is an employee and shareholder of MSD Italy. Dr Sieper has received grant/research support from Abbott, Merck, Pfizer and Janssen; is a consultant for Abbott, Merck, Pfizer, UCB, Roche, Lilly and Novartis; and is a member of the speakers bureau for Merck, Abbott, Pfizer and UCB. Dr Lenaerts has received honoraria from Abbott, BMS, MSD, Pfizer, Roche and AstraZeneca and consultancy or study fees from Pfizer, AbbVie, Novartis, Bristol-Myers-Squibb, Janssen-Cilag and Merck Sharp and Dohme. The other authors declared no conflicts of interest.
- Sieper J, Rudwaleit M, Lenaerts J, et al. Partial remission in ankylosing spondylitis and non-radiographic axial spondyloarthritis in treatment with infliximab plus naproxen or naproxen alone: associations between partial remission and baseline disease characteristics. Rheumatol Oxf Engl. 2016;55(11):1946-1953.
- Sieper J, Lenaerts J, Wollenhaupt J, et al. 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. Ann Rheum Dis. 2014;73(1):101-107.