Priyanka Vashisht1, Harlan Sayles1, Amy C Cannella1, Ted R Mikuls1, Kaleb Michaud2. 1. Priyanka Vashisht, MD, Harlan Sayles, MS, Amy C. Cannella, MD, MS, Ted R. Mikuls, MD, MSPH: VA Nebraska-Western Iowa Health Care System and Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, Nebraska. 2. Kaleb Michaud, PhD: VA Nebraska-Western Iowa Health Care System and Nebraska Arthritis Outcomes Research Center, University of Nebraska Medical Center, Omaha, Nebraska, and the National Bank for Rheumatic Diseases, Wichita, Kansas. kmichaud@unmc.edu.
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.
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 RApatients in the US have had biologic treatment exposure. We identified the proportion of RApatients 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 RApatients 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 RApatients and may provide insight into the differential responses to biologic agents reported in prior observational studies.
Authors: Robin K Dore; Jenya N Antonova; Chakkarin Burudpakdee; Lawrence Chang; Magdaliz Gorritz; Mark C Genovese Journal: ACR Open Rheumatol Date: 2021-11-18
Authors: Naomi H Martin; Fowzia Ibrahim; Brian Tom; James Galloway; Allan Wailoo; Jonathan Tosh; Heidi Lempp; Louise Prothero; Sofia Georgopoulou; Jackie Sturt; David L Scott Journal: Trials Date: 2017-12-08 Impact factor: 2.279