Comparative Effectiveness of Adalimumab vs Tofacitinib in Patients With Rheumatoid Arthritis in Australia.

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.

A novel electronic patient-reported outcome delivery system to implement health-related quality of life measures in routine clinical care: An analysis of 5 years of experience.

Objective: To develop a simple and secure technological solution to incorporate electronic patient-reported outcomes (ePROs) into routine clinical care. Methods: A novel ePRO questionnaire delivery system was developed by Software for Specialists (S4S) in partnership with OPAL Rheumatology Australia. Validated questionnaires were sent from the electronic medical record (EMR) (Audit4) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), lupus or giant cell arteritis (GCA) and delivered to the patient's email address or completed in the clinic waiting room using a smart device (in-practice). Completed questionnaires were encrypted and returned to the patient's Audit4. Deidentified clinical data was extracted and aggregated across all sites. Data collected between April 2016-Dec 2020 were analysed descriptively. Results: Between April 2016 to Dec 2020, 221,352 Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Patient Health Questionnaire-2 (PHQ-2) and/or HealthCare Resource Utilization (HCRU) questionnaires were sent from 39 of 42 contributing clinics (93%). 85% of questionnaires were delivered via email and 15% in-practice. Overall, 85% of patients completed at least one questionnaire, and of all questionnaires sent, 73% were completed. Females were more likely to engage with the questionnaires than males (87% vs. 81%), and older patients were slightly more likely to complete all questionnaires delivered. Conclusions: The novel Audit4 ePRO delivery system is an effective tool for incorporating PROs into routine clinical care. The data generated provides a unique opportunity to understand the full burden of disease for patients in the real-world setting and the impact of interventions.