Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE

Randomized controlled trials (RCTs) exist along a spectrum, from explanatory, designed to evaluate interventions under ideal conditions, to pragmatic, designed to reflect usual care. This study assessed the pragmatism of RCTs of advanced therapeutics in rheumatoid arthritis (RA).

METHODS

A systematic review was conducted to identify RA RCTs comparing biologic or targeted synthetic therapy in combination with methotrexate, to placebo or any other disease-modifying antirheumatic drugs (DMARDs). Trials were rated using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool in 9 domains, each rated from 1 (very explanatory) to 5 (very pragmatic). Latent class and regression analyses examined the heterogeneity in PRECIS-2 scores and the relationship to trial characteristics.

RESULTS

In total, 96 trials were included. Eligibility, follow-up, and flexibility of delivery of the intervention were rated as explanatory, with mean ± SD PRECIS-2 scores of 2.0 ± 0.7, 2.0 ± 1.1, and 2.1 ± 0.7, respectively, reflecting strict inclusion criteria, intensive follow-up, and rigid protocols. Studies were rated as pragmatic in setting (3.6 ± 1.5) because many were international, multicenter trials, and in primary analysis (4.1 ± 1.3), because most used intent-to-treat analyses. In latent class analyses, 2 groups were identified; the majority (74%) were rated as explanatory for most domains assessed. These trials had larger sample sizes, were more likely to be industry-funded, and enrolled patients with higher Disease Activity Score in 28 joints and Health Assessment Questionnaire disability index scores, but were less likely to be at high risk of bias.

CONCLUSION

RCTs of biologic DMARD treatment in combination with methotrexate for RA were rated as predominantly explanatory, which may affect the generalizability of trial results to clinical practice.