For demographics, the most common reason for trial exclusion was patients exceeding the disease duration maximum. On average, this aspect affected 10% of VARA patients and 2.5% of RAIN-DB patients across 20 of the trials. Additionally, a mean of 72% of VARA patients and 29% of RAIN-DB patients were excluded due to previous medication use. The authors write, “Prior methotrexate use, which excluded, on average, 16% in VARA and 6.8% in RAIN-DB, and the use of other disease-modifying anti-rheumatic drugs, which excluded, on average, 62% in VARA and 27% in RAIN-DB, were most striking.”
The authors note the importance of the aggressive treatment of RA, and in clinical practice, patients with fewer disease-affected joints are offered biologic agents as first-line therapy and/or when traditional disease-modifying anti-rheumatic drugs are not effective.
“These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients,” write the authors. “Patients recruited into these studies commonly have much higher levels of disease activity than seen in clinical practice, and comparator arms may include placebo. … However, when eligibility criteria are overly restrictive, [the criteria] can compromise external validity and sacrifice the generalizability of the results to the patient populations in whom the answer to the question is desired.”
The authors note the value of observational data for putting the results of randomized clinical trials in perspective. “There is a need for more real world/observational studies to guide prescribing protocols and provide comparative effectiveness of the many medications in treating patients with RA in clinical practice,” they conclude.
Vashisht P, Sayles H, Cannella AC, et al. Generalizability of patients with rheumatoid arthritis in biologic agent clinical trials. Arthritis Care Res (Hoboken). 68(10):1478–1488. doi: 10.1002/acr.22860.
