Tapering strategies of biological and targeted synthetic disease-modifying antirheumatic drugs for patients with inflammatory arthritis: a systematic review of randomised controlled trials

Lead Investigator: Line Uhrenholt, Aalborg University Hospital
Title of Proposal Research: Tapering strategies of biological and targeted synthetic disease-modifying antirheumatic drugs for patients with inflammatory arthritis: a systematic review of randomised controlled trials
Vivli Data Request: 6489
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Traditionally, standard dosage of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs, respectively) are continued lifelong in patients with inflammatory arthritis (i.e. rheumatoid arthritis [RA], psoriatic arthritis [PsA] and axial spondyloarthritis [axSpA]). However, recent studies indicate that a significant proportion of patients in sustained remission or low disease activity (LDA) can taper their bDMARD and maintain disease activity. This systematic review will evaluate the risk of flare i.e. worsening in arthritis activity after the dosage of biological drugs have been reduced or even discontinued in patients with inflammatory arthriris (e.g. rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis) in sustained remission or low disease activity. The review will only include randomised controlled trials as these trials have the highest level of evidence.

Statistical Analysis Plan:

A meta-analysis will be performed if the studies eligible for the qualitative synthesis in this SLR are sufficiently similar regarding study design, participants, interventions, comparators, and outcomes. We will estimate a relative risk for each trial (measured using hazard ratio, rate ratio, risk ratio, or odds ratio, in order of preference), computed from summary statistics and subgroups where necessary. Results in forest plots will be based on relative risk estimates with 95% confidence intervals. Meta-analyses will be based on random effects inverse variance weighted averages with a moment estimate of between studies variance, with the extent of inconsistency measured using I2 statis-tics (35,36) and between study heterogeneity represented in prediction intervals. We will present mean effects from random effects analyses in the text. Sensitivity analyses using alternative meta-analysis approaches will be presented in appendix materials.

Requested Studies:

A Multicenter, Randomized, Double-Period, Double − Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)
Sponsor: AbbVie
Study ID: NCT00420927
Sponsor ID: M06-810

Public Disclosure:

Line Uhrenholt, Robin Christensen, Wilfred K H Dinesen, Caroline H Liboriussen, Stine S Andersen, Lene Dreyer, Annette Schlemmer, Ellen-Margrethe Hauge, Conni Skrubbeltrang, Peter C Taylor, Salome Kristensen. Risk of flare after tapering or withdrawal of biologic/targeted synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or axial spondyloarthritis: a systematic review and meta-analysis. Rheumatology, 2021. doi: 10.1093/rheumatology/keab902