Background 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 also indicated for the treatment of PsA and 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 newer options with more traditional agents such as tumor necrosis factor inhibitors (TNFi).
Objectives The current analysis compares TOFA to TNFi used with and without methotrexate (MTX) among patients with RA.
Methods Data collected since January 1, 2014 (when TOFA became available in Canada) at the Institut de Recherche en Rhumatologie de Montréal (IRRM) and the Centre de l’Ostéoporose et de Rhumatologie de Québec (CORQ) was extracted from Rhumadata® on January 7, 2019. Patients initiated on TOFA or a TNFi (adalimumab, certolizumab, etanercept, golimumab, infliximab) without or with MTX were selected. Data include baseline characteristics (socio-demographic variables, concomitant and past medication, comorbidities and the Charlson comorbidity index (CCI)), variables measured over time (lab results, patient and physician-reported outcomes, and disease activity measures) 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 Cox methods.
Results A total of 480 patients were prescribed TOFA (n=162) or a TNFi (n=318) since January 1, 2014. Of those, 57% (n=92) and 70% (n=224) were treated with MTX in the TOFA and TNFi group respectively and mean disease duration was 12.1 (standard deviation=11.0) and 7.2 (8.1) years. TOFA and TNFi represent the first treatment following csDMARD-IR for 33%(TOFA) and 62%(TNFi). In the TOFA group, 84% were women, 15% were smokers and the mean age at treatment initiation was 57.7 (11.5) years. In the TNFi group, 77% were women, 12% were smokers and the mean age at treatment initiation was 54.2 (13.7) years. At treatment initiation, 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 5.0 (2.9), 5.5 (3.0) and 5.1 (3.1) in the TNFi group. Baseline disease activity was assessed as moderate or high/severe in 85.9% and 76.7% of TOFA (?) patients (DAS28(4)-ESR criteria). Among the 56 (35%) TOFA and 146 (46%) TNFi patients ceasing therapy, reasons for cessation were “inefficacy” (TOFA: 64% vs TNFi: 56%) and “adverse events” (TOFA: 16% vs TNFi: 11%). Patients remaining on TOFA and TNFi therapy at last follow-up had an average treatment duration of 1.7 (1.1) and 2.7 (1.5) years and no difference in retention was observed between TOFA and TNFi treated patients (log-rank p=0.41). Patients treated with a TNFi in combination with MTX had better treatment retention than those treated without MTX (log-rank p=0.04) while patients treated with TOFA+/-MTX had similar retention (log-rank p=0.96). These results remain unchanged when adjusted for gender, age at treatment initiation, disease duration, and comorbidities.
Conclusion In our real-world data registry, treatment with TNFi and TOFA yielded similar retention over time. Subjects treated with TNFi and MTX remained on treatment longer than those treated without MTX while subjects treated with tofacitinib with or without MTX had similar retention.
Disclosure of Interests 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
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