Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials

Arthritis Care Res (Hoboken). 2016 Oct;68(10):1478-88. doi: 10.1002/acr.22860. Epub 2016 Sep 16.


Objective: Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs.

Methods: Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure.

Results: The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4-7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date.

Conclusion: The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Factors / therapeutic use*
  • Eligibility Determination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patient Selection
  • Randomized Controlled Trials as Topic / methods
  • Randomized Controlled Trials as Topic / standards*
  • Research Design / standards*
  • Young Adult


  • Antirheumatic Agents
  • Biological Factors