Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Arthritis Care Res (Hoboken). 2021 Jun;73(6):861-872. doi: 10.1002/acr.24184.

Abstract

Objective: The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care.

Methods: We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow-up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety.

Results: We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C-reactive protein levels (MD 0.16 [95% CI -0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]).

Conclusion: Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / adverse effects
  • Drug Tapering
  • Female
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Remission Induction
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / administration & dosage*
  • Tumor Necrosis Factor Inhibitors / adverse effects
  • Young Adult

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor Inhibitors