The operational definition of old age and impact on outcomes in DMARD-treated patients with rheumatoid arthritis: A systematic literature review.

Objective: To systematically review operational definitions of old(er) age in rheumatoid arthritis (RA) patients and investigate differences in disease-modifying anti-rheumatic drug (DMARD) efficacy, safety and drug survival between young(er) and old(er) patients.

Methods: A systematic review was performed on studies conducting research in an old(er) RA patient population. Two reviewers independently performed data extraction and risk of bias assessment. Operational definitions of old(er) age were described using frequency statistics. For studies comparing effects of DMARDs, random effects meta-analyses estimated pooled odds ratios (ORs) of young(er) vs. old(er) patients reaching remission, experiencing adverse events (AEs) and discontinuing drug treatment due to unfavourable events.

Results: This review included 324 studies. The operational definition for old(er) age ranged from 40.0 to 77.3 years. The most frequent definition was 65 (45.1 %), followed by 60 years or older (20.4 %). Fifty-eight percent of studies reported no reason for using a specific age-threshold. Seventy-nine studies evaluated DMARD efficacy, safety and/or survival, with 37 eligible for meta-analysis. No statistically significant difference in reaching remission was observed between old(er) and young(er) patients (OR=0.76 (95 %-CI: 0.57-1.02)) (n = 11 studies). AEs and drug discontinuation were experienced more often in old(er) patients (OR=1.33 (95 %-CI: 1.01-1.74) (n = 19 studies) and OR=1.12 (95 %-CI: 1.02-1.23) (n = 25 studies), respectively).

Conclusion: Definitions of old(er) age vary across studies including RA patients. Old(er) age appears to affect DMARD safety and discontinuation. To ensure meaningful comparisons across studies, studies should justify the chosen definition and report and account for potential impacts of indicators of ageing, such as multimorbidity, polypharmacy, and geriatric syndromes.