Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia
Authors: Deakin Claire T. , De Stavola Bianca L. , Littlejohn Geoffrey , Griffiths Hedley , Ciciriello Sabina , Youssef Peter , Mathers David , Bird Paul , Smith Tegan , O’Sullivan Catherine , Freeman Tim , Segelov Dana , Hoffman David , Seaman Shaun R. ,   OPAL Rheumatology Network, Rischin Adam , Scott-Charlton Adam , Quinlivan Alannah , Stockman Alex , Capon Alexandra , Ananda Ana , Foote Andrew , Dorai-Raj Anna , Finniss Anna , Sweeney Aoife , Salonga Armi , Damodaran Arvin , Hennessey Ashleigh , Shenstone Bain , Kane Barry , Sutu Benjamin , Omidvar Bita , Nataraja Champa , Inderjeeth Charles , Tong Chiwai , Mack Chris , Barrett Claire , Sumpton Dan , Boulos Daniel , Lewis Daniel , Nicholls Dave , Mathers David , Speden Deb , Chessman Diana , MA Dickson , Ong Emily , Romas Evange , Laska Frank , Joshua Fred , Strickland Gemma , Ngian Gene-Siew , Littlejohn Geoff , Tracey Gerald , Griffiths Hedley , Cooley Helen , Telegdy Ildiko , Hutton Ingrid , Chay Jacky , Oliver Jane , Zochling Jane , Ly Jason , Moxey Jayne , Harmer Jennifer , Wang Jeremy , He Jianna , Hall Joanna , May John , Moi John , vander-Kallen John , Aw Juan , Pui Karen , Franklyn Kate , Gregory-Wong Kate , Tymms Kathy , Morrisroe Katie , Over Katy , Cai Ken , Khoo Ken , Maguire Ken , Langford Kiri , Dissanayake Kokum , Yap Kristy , Girgis Laila , Young Laurel , Alblas Leanne , Barnsley Les , Deveza Leticia , Voight Louisa , Croyle Lucy , Handel Malcolm , Turner Malcolm , Mundae Maninder , Micallef Maree , Feletar Marie , Arnold Mark , Collins Mark , Reynolds Mathew , Isbel Maxine , Szramka Maxine , Wong Melinda , Marabani Mona , Mian Mueed , Wood Nigel , Shamdasani Pallavi , Bird Paul , Mansfield Paul , Pentony Peta , Nash Pete , Youssef Peter , Buchbinder Rachelle , Penglase Ross , Jayalath Ruvinka , Ciciriello Sabina , Kempe Sarina , Fayez Sayed , Oon Shereen , Patel Shreeya , Sharma Shunil , Chatfield Simon , Joshi Sonam , Seah Stanley , Truong Steve , Jayaweera Suren , Tahir Talib , Tsai Ted , Godfrey Tim , Racunica Tina , Chang Winston , Loew Yuen , Papandony Michelle , Oh Yumi 
Published: June 2023

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.