In patients with early peripheral spondyloarthritis (pSpA) who attain a clinical response after 2 years of treatment with a tumor necrosis factor inhibitor (TNFi), stepdown treatment with methotrexate (MTX) monotherapy leads to high rates of clinical relapse, according to study results published in Rheumatology (Oxford).
Researchers sought to explore the possibility that co-medication with MTX would enable the discontinuation of TNFi therapy after attaining clinical remission at the end of a 2-year open-label extension period with golimumab treatment.
Researchers conducted an open-label extension phase of the CRESPA trial (ClinicalTrials.gov Identifier: NCT01426815) in Belgium. Patients included in the analysis were newly diagnosed adults with active pSpA with a symptom duration of less than 12 weeks and who met the Assessment of SpondyloArthritis International Society (ASAS) criteria for pSpA. Participants were eligible for the CRESPA extension protocol either if they had not attained sustained clinical remission at week 48 but were responders (defined as achieving pSpA 40% Response Criteria) or if after reaching sustained clinical remission with golimumab, they experienced a recurrence of arthritis, enthesitis, or dactylitis within 1 year of golimumab discontinuation.
Patients in the CRESPA extension protocol received golimumab 50 mg every 4 weeks, for a total of 104 weeks. At the end of the extension phase, all participants were offered a stepdown strategy that included 12 weeks of additional golimumab therapy plus oral MTX 15 mg per week. At week 116, only those patients who were in clinical remission — those who experienced the complete absence of arthritis, enthesitis, and dactylitis — continued to receive MTX treatment. All participants were prospectively followed up to evaluate the rate of sustained biologic-free clinical remission — the study endpoint, which was defined as the total absence of arthritis, enthesitis, and dactylitis on clinical examination. Golimumab treatment was restarted if a relapse of arthritis, enthesitis, or dactylitis was reported, or if patients exhibited MTX intolerance.
A total of 31 of 60 patients with pSpA in the CRESPA study were eligible for inclusion in the current analysis, with 25 consenting to the stepdown strategy. Among these patients, 16% (n=4) remained in clinical remission with MTX monotherapy. In 84% (n=21) of the patients, golimumab was reinitiated because of relapse of disease activity (n=19) or the development of adverse events related to MTX treatment (n=2). Once golimumab treatment was restarted, clinical remission was restored among all patients within 12 weeks.
One of the study limitations was the lack of MTX uptitration.
Researchers concluded that the results of the extension study demonstrated the overall weak efficacy of MTX in maintaining clinical remission in patients with pSpA.
They added that the clinical heterogeneity of pSpA highlighted the need for additional research to evaluate the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic DMARDs, and targeted synthetic DMARDs in well-designed, randomized trials across the pSpA spectrum.
Disclosure: This clinical trial was supported by Janssen Pharmaceutica NV. Please see the original reference for a full list of authors’ disclosures.
Philippe C, Ann-Sophie C, Thomas R, Roos C, Dirk E, Filip VDB. TNFi-induced sustained clinical remission in peripheral spondyloarthritis patients cannot be maintained with a step-down strategy based on methotrexate. Rheumatology (Oxford). Published online January 20, 2021 doi:10.1093/rheumatology/keab056