Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials

Priyanka Vashisht, Harlan Sayles, Amy C Cannella, Ted R Mikuls, Kaleb D Michaud

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1478-1488
Number of pages11
JournalArthritis Care and Research
Volume68
Issue number10
DOIs
StatePublished - Oct 1 2016

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Biological Factors
Rheumatoid Arthritis
Randomized Controlled Trials
Clinical Trials
Joints
Drug Approval
Rheumatology
Veterans
Arthritis
Observational Studies
Registries
Publications
Necrosis
Demography
Databases
Food
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Rheumatology

Cite this

Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials. / Vashisht, Priyanka; Sayles, Harlan; Cannella, Amy C; Mikuls, Ted R; Michaud, Kaleb D.

In: Arthritis Care and Research, Vol. 68, No. 10, 01.10.2016, p. 1478-1488.

Research output: Contribution to journalArticle

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abstract = "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.",
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