Background International task forces recommend conventional disease-modifying antirheumatic drugs (DMARDs) as first-line therapy in patients (pts) with rheumatoid arthritis (RA).1,2 In some pts, treatment with a biologic DMARD as monotherapy (MT) may provide clinical benefit without the potential undesirable side effects associated with conventional DMARDs; however, research on the persistency of biologic initiations as MT is limited.
Objectives To estimate the persistency of biologic use as MT using combination therapy (CMB) as a reference and to examine predictors of MT persistency in pts with RA participating in the Consortium of Rheumatology Researchers of North America (CORRONA) registry.
Methods Pts in CORRONA who initiated their first use of a particular biologic as on-label MT or in combination with methotrexate (MTX) between 2007 and 2013 were eligible for inclusion in this analysis. Unadjusted Kaplan-Meier analyses were performed to estimate the rates of persistency and failure (end of therapy) for all MT and CMB initiations. Failure of persistency was defined as any modification to a particular biologic initiation as MT or CMB, including switch/discontinuation of the biologic or addition/switch/discontinuation of conventional DMARD. Cox regression models were used to examine predictors of MT persistency. Factors from the unadjusted analysis significantly associated with persistency (P<0.2) and with <3% missing data were included in the full adjusted model.
Results There were 4422 eligible initiations, including 1518 MT and 2904 CMB initiations. At baseline, mean ± SD age was similar between pts initiating MT vs CMB (56.0±12.7 vs 56.1±13.4 years); however, MT initiators had longer mean ± SD duration of RA (10.3±9.4 vs 9.4±9.5 years; P<0.01) and higher mean ± SD clinical disease activity index (CDAI; 21.9±15.1 vs 20.7±14.2; P<0.05). Of MT initiators who previously discontinued MTX, reasons included toxicity (51.6%), loss of efficacy (17.4%) and other (e.g. insurance, pt preference etc; 45.3%). Unadjusted comparison of rates of persistency at 12, 24 and 36 months were in favor of CMB initiations (Figure). Factors associated with failure of MT persistency included shorter disease duration (HR 0.93; [95% CI 0.86, 0.99] per 10 years), previous smoking status (HR 1.23; 95% CI 1.05, 1.43), prednisone dose ≥10 mg (HR 1.31; 95% CI 1.06, 1.61), increased pt assessment of pain (HR 1.05; [95% CI 1.02, 1.07] per 10 units) and higher CDAI (HR 1.06; [95% CI 1.01, 1.11] per 10 units). The treatment modifications resulting in end of MT persistency were addition of a conventional DMARD (31.6%), switch of the biologic (32.9%), discontinuation of the biologic (22.4%) and switch to a conventional DMARD (13.0%).
Conclusions The proportion of pts remaining on their initiated biologic treatment decreased over time in both groups. Several clinical characteristics were associated with increased persistency of MT. Further analyses will investigate differences across individual biologics.
Singh JA, et al. Arthritis Care Res (Hoboken). 2012;64:625-39.
Smolen JS, et al. Ann Rheum Dis. 2013 Oct 25. [Epub ahead of print].
Acknowledgements This study is sponsored by CORRONA. In the last 2 years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex and UCB have supported CORRONA through contracted subscriptions.
Disclosure of Interest D. Pappas Employee of: CORRONA, Inc., Paid instructor for: Novartis., A. John Employee of: Genentech, Inc., G. Reed Employee of: CORRONA, Inc., C. Karki Employee of: CORRONA, Inc., J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca and Pfizer., A. Shewade Employee of: Genentech, Inc., J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc.