Background TNF inhibitors (TNFi) can be used as monotherapy (mono) or in combination (combo) with conventional DMARDS (cDMARDS). Clinical trial data and European registry data have shown evidence of better effectiveness of TNFi combo therapy than mono. Effectiveness of mono vs combo in US clinical practice, in particular among biologic naïve and experienced patients, has not been assessed.
Objectives This study was carried out to quantify the prevalence and effectiveness of TNFi monotherapy use in US clinical practice. A secondary objective was to contrast this with tofacitinib (tofa) monotherapy use and effectiveness.
Methods RA patients initiating a TNFi (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) or tofa with a six month follow-up in Corrona US were identified. A subcohort of TNFi initiations after 11/6/2012 (market approval of tofa) were used for comparisons with tofa initiators. We defined combo therapy as TNFi or tofa used with MTX alone and mono as no use of any cDMARD. The primary outcome was achieving low disease activity (LDA) or remission based on CDAI (≤10) at 6 months. Patients switching to another biologic prior to 6 months were defined as non-responders. Secondary outcomes included modified ACR20/50/70 and mean change in CDAI. Combo and mono initiators were matched within line of therapy using a propensity score. Covariates for the model were selected if the standardized mean difference between the groups >0.1.
Results There were 7076 TNFi initiations in Corrona, with 2091 (30%) mono initiations. Mono by line of therapy was 21%, 35% and 41% for 2nd, 3rd and 4th line therapy, respectively. There were 325 tofa initiations with 201 (61%) mono and mono rates of 50%, 65% and 63% for 2nd, 3rd and 4th line therapy, respectively. In the matched populations, across outcome measures (Table 1), TNFi combo was more effective than TNFi mono in 2nd line therapy (55.6% LDA vs 47.1% LDA) and similar in 3rd and 4th line therapy. Tofa combo therapy was similar to mono in the matched populations (35.4% LDA vs 32.3% LDA). Tofa mono was similar to TNFi combo therapy in the matched populations (33.3% LDA vs 33.3% LDA).
Conclusions TNFi monotherapy is common in U.S. clinical practice. TNFi monotherapy is less effective than combination therapy especially in biologic naïve patients. There is no evidence that tofa monotherapy is less effective than tofa combination therapy or TNFi combination therapy.
Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.
Disclosure of Interest G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Gerber Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., Y. Shan Employee of: Corrona, LLC, L. Takiya Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., K. Dandreo Employee of: Corrona, LLC, D. Gruben Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), G. Wallenstein Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc.