SAT0140 COMPARATIVE EFFECTIVENESS OF TOFACITINIB AND NON-TNF AGENTS SINCE 2014. IMPACT OF COMBINATION WITH METHOTREXATE
Authors: Denis Choquette, Louis Bessette, Loïc Choquette Sauvageau, Isabelle Ferdinand, Paul Haraoui, Frédéric Massicotte, Jean-Pierre Pelletier, Jean-Pierre Raynauld, Marie-Anaïs Rémillard, Diane Sauvageau, Édith Villeneuve, Louis Coupal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Tofacitinib (TOFA), a targeted synthetic DMARD, has been approved for the treatment of rheumatoid arthritis (RA) in Canada since April 2014. This oral agent preferentially inhibits signalling by cytokine receptors associated with JAK1 and JAK3 subunits. It is now indicated for the treatment of psoriatic arthritis (PsA) and ulcerative colitis (UC) since October 2018. Clinical experience with this molecule has been increasing, and questions relating to its efficacy and long-term safety are of interest. Data collection through RHUMADATA®, a Quebec based clinical database and registry, allows comparison of various advanced treatment options including TOFA and non-TNFi biologic agents (i.e., agents with other modes of action - OMA) such as fusion proteins (abatacept), and IL-6 (sarilumab, tocilizumab) and CD20 inhibitors (rituximab). <h3>Objectives</h3> This analysis compares TOFA and OMAs used with and without methotrexate (MTX). <h3>Methods</h3> Data collected since January 1, 2014 (since TOFA became available in Canada) at the <i>Institut de Recherche en Rhumatologie de Montréal</i> (IRRM) and the <i>Centre de l'Ostéoporose et de Rhumatologie de Québec</i> (CORQ) was extracted from the Rhumadata® on January 7, 2019. The selected patients had initiated therapy with either TOFA or OMA (either without or in combination with MTX). The collected data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (laboratory test results, patient and physician-reported outcomes, and disease activity measures such as CDAI and DAS28(4)-ESR) and persistence data (treatment duration, reason for cessation). The groups were compared to identify potential confounder, and persistence data were analyzed using Kaplan-Meier and proportional hazard methods. <h3>Results</h3> A total of 483 patients were initiated on TOFA (n=162) or an OMA (n=321) since January 1, 2014. Of those, 57% (n=92) and 59% (n=191) were treated with MTX in the TOFA and OMA group respectively. These represent the first treatment following csDMARD inadequate response for 33%(TOFA) and 29%(OMA) of these patients. These patients had a mean disease duration of 12.1 (standard deviation=11.0) and 11.1 (10.3) years. In the TOFA group, 84% were women, 15% were smokers, and the mean age at treatment initiation was 57.7 (11.5). In the OMA group, 75% were women, 18% were smokers, and the mean age at treatment initiation was 57.3 (12.0) years. Patient global, pain and fatigue assessments, made on a visual analogue scale ranging from 1 to 10, were 5.6 (2.5), 5.9 (2.7) and 5.7 (2.9) in the TOFA group and 5.7 (2.5), 6.1 (2.7) and 6.0 (2.8) in the OMA group. Disease activity was assessed as moderate or high/severe in 85.9% and 88.3% of patients (DAS28(4)-ESR criteria). Among the 56 (35%) TOFA and 149 (46%) OMA patients ceasing therapy, reasons for cessation were "inefficacy" (TOFA: 64% vs OMA: 59%) and "adverse events" (TOFA: 16% vs TNFi: 17%). Patients remaining on TOFA and OMA therapy at last follow-up had an average treatment duration of 1.7 (1.1) and 2.6 (1.4) years. No difference in retention was observed between TOFA and OMA treated patients (log-rank p=0.6138). Patients treated with an OMA+/-MTX had similar retention (log-rank p=0.2640) as did patients treated with TOFA+/-MTX (log-rank p=0.9553). These results remain unchanged when we adjust for age at treatment initiation, gender, disease duration, and comorbidities (CCI) using Cox models. <h3>Conclusion</h3> OMA and TOFA have similar retention as do subjects treated with OMA or TOFA with or without MTX. <h3>Disclosure of Interests</h3> Denis Choquette Grant/research support from: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Celgene, Eli Lilly, Novartis, Pfizer Inc, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant for: AbbVie, Amgen, Novartis, Pfizer, Speakers bureau: Amgen, Pfizer, Paul Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Consultant for: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Speakers bureau: Pfizer, Frédéric Massicotte Consultant for: AbbVie, Pfizer, Janssen, Eli Lilly, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: Shareholder in ArthroLab Inc., Grant/research support from: Study funded by TRB Chemedica SA, Consultant for: TRB Chemedica SA, Jean-Pierre Raynauld Consultant for: ArthroLab Inc., Marie-Anaïs Rémillard Consultant for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant for: AbbVie, UCB, Celgene, Roche, Pfizer, Amgen, BMS, Sanofi-Genzyme, Paid instructor for: AbbVie, Speakers bureau: AbbVie, Pfizer, BMS, Roche, Louis Coupal: None declared