Factors influencing prescribing the first add-on disease-modifying antirheumatic drugs in patients initiating methotrexate for rheumatoid arthritis

BACKGROUND: Advances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX. METHODS: This retrospective cohort study utilized the MarketScan data (2012–2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with continuous enrollment for the 6-month pre-index period. The combination therapy users received the first treatment addition of DMARD starting from day 30 after the index MTX over one year period. The study focused on the addition of csDMARDs, Tumor Necrosis Factor Inhibitors (TNFi) bDMARDs, non-TNFi bDMARDs, or tsDMARDs. Baseline covariates were measured in the 6-month pre-index and grouped into predisposing, enabling, and need factors, as per the Andersen Behavior Model. Multivariable logistic regression examined the factors associated with the addition of TNFi compared to adding a csDMARD. An additional regression model evaluated the factors associated with adding any biologic (combining TNFi and non-TNFi biologics). RESULTS: Among 8350 RA patients starting MTX, 31.92% (n = 2665) initiated any DMARD within the 1-year post-index period. Among RA patients initiating a DMARD prescription after starting MTX, 945 (11.32%) received combination therapy with treatment addition of a DMARD to MTX regimen; majority added TNFi (550, 58%), followed by csDMARD (352, 37%); non-TNF biologic (40, 4%), or tsDMARD (3, 0.3%). The tsDMARD group was limited and was not included for further analysis. The multivariable model found Preferred Provider Organization insurance coverage (odds ratio [OR], 1.43; 95% confidence interval (CI), 1.06–1.93), chronic pulmonary disease (OR, 1.98; 95% CI, 1.14–3.44), liver disease (OR, 5.24; 95% CI, 1.77–15.49), and Elixhauser score (OR, 0.91; 95% CI, 0.86–0.97) were significantly associated with the addition of TNF-α inhibitors. The separate multivariable model additionally found that patients from metropolitan areas (OR, 1.50; 95% CI, 1.04–2.16) were positively associated with adding any biological agent. CONCLUSIONS: TNFi are often added to MTX for managing RA. Enabling and need factors contribute to the prescribing of a TNFi add-on therapy in RA. Future research should examine the impact of these combination therapies on RA management.