Background Despite the availability of multiple therapies for treatment of RA in the US, there exists a high rate of discontinuation/change of therapy. This may be attributed to multiple factors including: loss of efficacy, adverse effects, patient/physician preference, access and/or expectation bias. This study was designed to examine initiation of biologic therapies within the US CORRONA database and characterize reasons for their discontinuation.
Methods In the CORRONA registry, patients meeting the following criteria during calendar years 2002-2011 were included: age >18; RA onset age >16 years; and ≥6 months follow-up after initiation of first or subsequent biologic therapy, defined as a visit ≥180 days after initiation of biologic therapy. Biologic agents included TNF inhibitors (TNFi’s) and non-TNFi‘s. Treatment discontinuation was defined as the first report of stopping initial therapy or initiation of a new biologic at/or between visits on a follow-up MD questionnaire. Up to 3 reasons for discontinuation were captured.
Results 6209 patients (78.5% female; mean age 57.6±12.8, median RA duration 8 years; 43.4% biologic naïve, 26.1% CDAI >22) met inclusion criteria. 5010 (80.7%) were receiving TNFi’s and 1199 (19.3%) non-TNFi’s. Overall median time to discontinuation/change of therapy was 25.1 months: 82.2% remained on initiated treatment at 6 months and 67.3% at 1 year. Median time to discontinuation was 26.5 months in those receiving TNFi’s (n=5010) vs 20.5 months for non-TNFi’s (n=1199) [log rank p<0001]. Overall proportions of patients receiving TNFi’s vs non-TNFi’s remaining on treatment were 82.5%, 68.2% and 52.2% at 6, 12, and 24 months vs 80.9%, 63.4% and 46.0%, respectively. Of 3584 discontinuations, reasons were captured for 1763 including: loss of efficacy: 35.8%; safety: 20.1%; MD/patient preference: 27.8%/ 17.9% and access to treatment: 9.0%. In patients receiving TNFi’s: percentages were 34.2, 20.8, 27.5, 17.9 and 9.6% and non-TNFi’s: 44.2, 16.8, 29.1, 17.9 and 6.0% respectively. Those 5010 initiating TNFi’s had shorter RA duration, lower disease activity, mHAQ, pain and fatigue scores than 1199 initiating non-TNFi’s. Biologic naïve patients (n=2693) had slightly higher durability although not significant [log-rank p=0.0601]. In multivariate analyses, the strongest predictors of discontinuation were higher CDAI and mHAQ scores, patient report of anxiety/depression, and year of biologic initiation.
Conclusions Patients in the US discontinue roughly 1/3rd of biologic therapies at 1 year, and 1/2 by 2 years. Rates and recorded reasons for treatment discontinuation were similar for both TNFi’s and non-TNFi biologics. Lack of efficacy was the single most common reason for discontinuation, although others reported were multifactorial and in part reflect expectations on the part of both patients and physicians.
Disclosure of Interest V. Strand Consultant for: CORRONA, Inc., S. Williams Shareholder of: AstraZeneca, Employee of: AstraZeneca, P. Miller Shareholder of: AstraZeneca, Employee of: AstraZeneca, K. Saunders Employee of: CORRONA, Inc., S. Grant Employee of: Axio Research LLC, J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc.