Background A recent randomized controlled trial in patients with rheumatoid arthritis (RA) showed non-inferiority of clinical benefit when starting on triple therapy (sulfasalazine (SSZ)+hydroxychloroqiune (HCQ)+methotrexate (MTX)) as compared to etanercept (ETN) and MTX in combination among highly adherent patients (taking >80% of medication) over a 48-week period.1 In addition, the study did not report persistence and real-world persistence with triple therapy is unknown.
Objectives To estimate 1-year adherence and persistence with triple therapy and ETN + MTX combination therapy in adult RA patients in a commercially-insured population in the US.
Methods Adults with RA newly initiating ETN+MTX combination therapy or triple therapy (MTX+HCQ+SLZ) were identified in the Truven Health MarketScan® Commercial and Medicare Supplemental Databases from January 2009-July 2012. The index date was the start of ETN for the ETN+MTX cohort; a 28-day overlap of days of supply was required to assure combination use of ETN+MTX. Triple therapy was defined as having at least 28 days overlapping use of MTX, HCQ, and SLZ, measured from the first date for the third therapy (index date); triple therapy patients could start MTX, HCQ, and SLZ in any order (including simultaneously) but could not have pre-index use of the third agent. Patients were required to be enrolled in their health plan for 6-months pre- and 12-months post-index, have a pre-index RA diagnosis, no pre-index biologic use, and no other diagnoses where the study drugs are FDA-approved. Patients with other non-biologic DMARDs (e.g., leflunomide) within 30 days of the index date were excluded. Outcomes included adherence and persistence. Adherence was defined as having Percent of Days Covered (PDC)>80% for each therapy [(ETN and MTX)/(MTX and HCQ and SLZ)]. For ETN+MTX, non-persistence was defined as a 45 day gap in ETN or MTX or switching biologic agents. For triple therapy, non-persistence was defined as a 45 day gap in MTX, HCQ, or SLZ or initiating a biologic agent. Gaps were measured following the end of the previous days supply, appending extra from prior prescriptions to early refills. Sensitivity analysis was conducted using gap lengths of 15, 30, and 60 days.
Results A total of 3,724 ETN+MTX patients (mean age 52, 78% female) and 818 triple therapy patients (mean age 55, 74% female) met the selection criteria. After 12 months, 53% more ETN+MTX patients were adherent relative to those on triple therapy (27.9% vs. 18.2%, p<0.0001). In the ETN+MTX group, 49.7% were adherent on ETN and 45.4% on MTX compared to 32.8% adherent on SSZ, 52.6% on HCQ and 55.7% on MTX individually. Adherence dropped to between 23.3% and 36.2% when factoring in a second agent in the triple therapy group. ETN+MTX patients were 24% more likely to be persistent than triple therapy patients (23.7% vs. 19.1%, p=.005). Overall, 25.7% of triple therapy patients switched to biologic therapy compared to 19.5% of ETN+MTX patients (p<.001) switching biologic agents.
Conclusions In this real-world analysis, patients initiating treatment on ETN+MTX had greater adherence and persistence than those initiating on triple therapy.
O'Dell et al. N Engl J Med 2013;369:307-18.
Acknowledgements Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc.
Disclosure of Interest : M. Bonafede: None declared, B. Johnson: None declared, D. Tang Shareholder of: Amgen, Employee of: Amgen, N. Shah Shareholder of: Amgen, Employee of: Amgen, D. Harrison Shareholder of: Amgen, Employee of: Amgen, D. Collier Shareholder of: Amgen, Employee of: Amgen