Many randomized controlled trials that examine the treatment of rheumatoid arthritis (RA) with biologic disease-modifying antirheumatic drugs (DMARDs) and methotrexate are explanatory with very controlled conditions, according to results published in Arthritis Research and Care. The explanatory nature of these studies may affect the ability to generalize their results to clinical practice.
The systematic review included 96 randomized controlled trials that compared biologic or targeted synthetic therapy in combination with methotrexate with placebo or any other DMARDs. The researchers rated the trials using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool in 9 domains, rated from 1 (very explanatory) to 5 (very pragmatic).
The researchers rated most trials as explanatory, especially in the domains of eligibility, follow-up, and flexibility of delivery of the intervention. Mean PRECIS-2 scores for each of the domains were 2.0, 2.0, and 2.1, respectively, which indicate strict inclusion criteria, intensive follow-up, and rigid protocols.
The researchers rated most trials as pragmatic in terms of setting (mean score, 3.6), because many of the trials were international, multicenter trials. The trials were also rated as pragmatic in primary analysis (mean score, 4.1) because most used intention-to-treat analysis.
The majority (74%) of trials were rated as predominately explanatory. These studies tended to have larger sample sizes, funding from the industry, and participants with higher Disease Activity Score of 28 joints and health assessment questionnaire disability index scores.
“Moving forward, more pragmatic comparative effectiveness trials should be encouraged. The results from these more pragmatic studies would help inform clinicians and patients about the relative benefits and risks of active treatments to improve informed choice and patient outcomes,” the researchers wrote.
Choi MY, Barnabe C, Barber CE. Randomized controlled trials of biologic treatment with methotrexate in RA may not reflect real world practice: a systematic review and assessment of pragmatism. [published online June 15, 2018]. Arthritis Care Res. doi:10.1002/acr.23620