At the American College of Rheumatology Convergence, researchers presented a study in which they sought to identify demographic, clinical, and disease activity predictors of difficult-to-treat rheumatoid arthritis (D2T-RA) in patients with established disease undergoing their first treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). 

Data were drawn from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective registry. The study included patients treated with a first-line b/tsDMARD, with the index date defined as the earliest BRASS visit documenting such therapy. D2T-RA was classified using EULAR 2021 criteria, and participants had at least one follow-up visit. Multiple imputation addressed missing values for potential predictors, and Cox proportional hazards (PH) models identified predictors of D2T-RA onset. Hazards ratios (HRs) and 95% confidence intervals were reported for both unadjusted and multivariable-adjusted models.

The study included 662 participants from 1581 enrollees in BRASS who met the inclusion criteria for first-line b/tsDMARD therapy. Patient demographics showed a median age of 56 years (IQR 46–65), and were predominantly female (84%) non-Hispanic White (91%), with a median disease duration of 9 years (IQR 4–20). Over a median follow-up period of 60 months (IQR 36–120), 113 patients (17%) developed D2T-RA. 

The final multivariable-adjusted model, with a C-index of 0.705, identified key predictors of D2T-RA. Obesity (BMI >30 kg/m², HR=1.65), concurrent prednisone use (HR=1.48), higher patient global activity scores (HR=1.15 per unit increase), and elevated MDHAQ fatigue scale scores (HR=1.01 per 5-unit increase) were associated with an increased risk of developing D2T-RA. Conversely, concurrent methotrexate use was protective, reducing the hazard by 36% (HR=0.64).

Predictors of D2T-RA included clinical factors such as obesity, prednisone use, and the absence of concurrent methotrexate therapy, along with patient-reported outcomes such as higher fatigue and disease activity levels. These findings underscore the need for targeted interventions to address modifiable risk factors such as obesity and glucocorticoid use. 

The study highlights the importance of individualized treatment strategies for RA, particularly for mitigating risks of D2T-RA. Further research should explore subphenotypes of inflammatory and noninflammatory D2T-RA to better understand underlying mechanisms and guide therapeutic decisions. By addressing both clinical and patient-reported factors, clinicians may improve outcomes for this challenging subset of patients with RA.

Reference
Paudel M. Obesity, prednisone use, and patient-reported outcomes are predictors of becoming difficult-to-treat in an RA population treated with a first-line biologic DMARD. Presented at: American College of Rheumatology. November 14-19, 2024; Washington, DC.