Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia
Claire T. Deakin, Bianca De Stavola, Geoffrey Littlejohn, Hedley Griffiths, Sabina Ciciriello, Peter Youssef, David A. Mathers, Paul Bird, Tegan Smith, Catherine O’Sullivan, Tim Freeman, Dana Segelov, David Hoffman, Shaun R. Seaman, OPAL Rheumatology Network, Adam Rischin, Adam Scott-Charlton, Alannah Quinlivan, A. Stockman, Alexandra Capon, Ana Ananda, Andrew Foote, Anna Dorai-Raj, Anna Finniss, Aoife Sweeney, Armi Salonga, Arvin Damodaran, Ashleigh Hennessey, Bain Shenstone, Barry Kane, Benjamin Sutu, Bita Omidvar, Champa Nataraja, Charles Inderjeeth, Chiwai Tong, Chris Mack, Claire Barrett, Dan Sumpton, Daniel Boulos, Daniel J. Lewis, Dave Nicholls, David A. Mathers, Deb Speden, Diana Chessman, Dickson MA, Emily Ong, Evange Romas, Frank J. Laska, Fredrick Joshua, Gemma Strickland, Gene‐Siew Ngian, Geoff Littlejohn, Gerald Tracey, Hedley Griffiths, Helen Cooley, Ildiko Telegdy, Ingrid Hutton, Jacky Chay, Jane Oliver, Jane Zochling, Jason Ly, Jayne Moxey, Jennifer Harmer, Jeremy Wang, Jianna He, J. N. Hall, John M. May, John Moi, John vander-Kallen, Juan Aw, Karen Pui, Kate Franklyn, Kate Gregory-Wong, Kathy Tymms, Katie Morrisroe, Katy Over, Ken Cai, Ken Khoo, Ken Maguire, Kiri Langford, Kokum Dissanayake, Kristy Yap, Laila Girgis, Laurel Young, Leanne Alblas, Les Barnsley, Leticia A. Deveza, Louisa Voight, Lucy Croyle, M. Händel, Malcolm E. Turner, Maninder Mundae, Maree Micallef, Marie Feletar, Mark Arnold, Mark Collins, Matthew J. Reynolds, Maxine Isbel, Maxine Szramka, Melinda Wong
Abstract
Importance: There is a need for observational studies to supplement evidence from clinical trials, and the target trial emulation (TTE) framework can help avoid biases that can be introduced when treatments are compared crudely using observational data by applying design principles for randomized clinical trials. Adalimumab (ADA) and tofacitinib (TOF) were shown to be equivalent in patients with rheumatoid arthritis (RA) in a randomized clinical trial, but to our knowledge, these drugs have not been compared head-to-head using routinely collected clinical data and the TTE framework. Objective: To emulate a randomized clinical trial comparing ADA vs TOF in patients with RA who were new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Design, Setting, and Participants: This comparative effectiveness study emulating a randomized clinical trial of ADA vs TOF included Australian adults aged 18 years or older with RA in the Optimising Patient Outcomes in Australian Rheumatology (OPAL) data set. Patients were included if they initiated ADA or TOF between October 1, 2015, and April 1, 2021; were new b/tsDMARD users; and had at least 1 component of the disease activity score in 28 joints using C-reactive protein (DAS28-CRP) recorded at baseline or during follow-up. Intervention: Treatment with either ADA (40 mg every 14 days) or TOF (10 mg daily). Main Outcomes and Measures: The main outcome was the estimated average treatment effect, defined as the difference in mean DAS28-CRP among patients receiving TOF compared with those receiving ADA at 3 and 9 months after initiating treatment. Missing DAS28-CRP data were multiply imputed. Stable balancing weights were used to account for nonrandomized treatment assignment. Results: A total of 842 patients were identified, including 569 treated with ADA (387 [68.0%] female; median age, 56 years [IQR, 47-66 years]) and 273 treated with TOF (201 [73.6%] female; median age, 59 years [IQR, 51-68 years]). After applying stable balancing weights, mean DAS28-CRP in the ADA group was 5.3 (95% CI, 5.2-5.4) at baseline, 2.6 (95% CI, 2.5-2.7) at 3 months, and 2.3 (95% CI, 2.2-2.4) at 9 months; in the TOF group, it was 5.3 (95% CI, 5.2-5.4) at baseline, 2.4 (95% CI, 2.2-2.5) at 3 months, and 2.3 (95% CI, 2.1-2.4) at 9 months. The estimated average treatment effect was -0.2 (95% CI, -0.4 to -0.03; P = .02) at 3 months and -0.03 (95% CI, -0.2 to 0.1; P = .60) at 9 months. Conclusions and Relevance: In this study, there was a modest but statistically significant reduction in DAS28-CRP at 3 months for patients receiving TOF compared with those receiving ADA and no difference between treatment groups at 9 months. Three months of treatment with either drug led to clinically relevant average reductions in mean DAS28-CRP, consistent with remission.