Biologic discontinuation studies: a systematic review of methods

Area of Science:

• Rheumatology
• Clinical Trial Design
• Pharmacotherapy

Background:

• Biologic therapies are crucial for managing rheumatoid arthritis (RA).
• Understanding outcomes after discontinuing biologics is essential for treatment optimization.
• Existing studies on biologic discontinuation in RA exhibit considerable heterogeneity.

Purpose of the Study:

• To systematically review the study designs employed in biologic discontinuation research for rheumatoid arthritis (RA).
• To critically assess the various definitions of 'failure' used in these studies.
• To identify limitations and areas for improvement in the design of RA biologic discontinuation trials.

Main Methods:

• A systematic literature search was conducted on PubMed, identifying 403 studies.
• Nine published papers and five abstracts were included for detailed analysis.
• A structured data extraction form was utilized to collect information on study design and failure definitions.

Main Results:

• Three main study types were identified: randomized controlled trials, long-term extension studies, and prospective discontinuation studies.
• The majority of studies permitted the concurrent use of non-biologic disease-modifying antirheumatic drugs (DMARDs).
• Significant heterogeneity was observed in failure definitions, with differing thresholds and time points for assessing disease activity, and limited incorporation of changes in non-biologic DMARD or glucocorticoid use.

Conclusions:

• While numerous studies address biologic discontinuation in RA, they are generally characterized by small sample sizes.
• Registries may offer valuable real-world data but necessitate broader, more inclusive definitions of treatment failure.
• Standardization of failure definitions is crucial for enhancing the comparability and interpretability of findings across studies.