Trial Exclusions May Skew RA Drug Comparisons

Nearly 40% of registry patients would have been excluded from phase 3 randomized controlled trials, with exclusion criteria distributed unevenly across drug classes.

By
Andrea Surnit
June 12, 2026
5 min

MDSpire News

Objective:

To analyze the outcomes of rheumatoid arthritis patients who would have been excluded from phase 3 randomized controlled trials when treated with biologic or targeted synthetic disease-modifying antirheumatic drugs in routine care.

Approach:

Key Findings:

40% of patients met at least one exclusion criterion, with anemia and lymphopenia being the most common.
Patients meeting exclusion criteria had higher baseline disease activity and greater functional disability.
After propensity score adjustment, remission rates were similar between groups: 24% for patients with no exclusion criteria and 23% for those with at least one criterion.
Janus kinase inhibitors showed higher remission rates compared to tumor necrosis factor inhibitors among patients who met no exclusion criteria.

Interpretation:

Limitations:

The observational design limits causal inference and residual confounding could not be excluded.
The definition of trial ineligibility was restricted to variables captured in the registry, omitting some exclusions like psychiatric disorders and pregnancy intention.
Findings may not be generalizable outside Japan due to differing methotrexate practices and patient characteristics.