Opal Rheumatology Ltd.

To describe the demographics, disease burden and real-world management of patients with systemic lupus erythematosus (SLE) in Australian community practice.

Patients with a physician diagnosis of SLE and at least 1 visit between 1 January 2009 and 31 March 2021 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 112 Australian rheumatologists. Demographics, basic clinical features and prescribed medications were described, with medication combinations used as a surrogate of disease severity.

Of 5133 patients with a diagnosis of lupus, 4260 (83%) had SLE. Of these SLE patients, almost 90% of patients were female, with a median age of 49 years [IQR 37-61] at first-recorded visit. Of the 2285 SLE patients whose most recent visit was between 1 January 2019 and 31 March 2021, 52.5% had mild disease, 29.9% had moderate-severe disease and 7.4% had very severe disease. Visit frequency increased with disease severity. Most patients (85.8%) were treated with hydroxychloroquine, typically prescribed as first line-of-therapy.

In this large real-world Australian cohort of patients with SLE, a substantial burden of disease was identified, with a significant proportion (almost one-third of patients) considered to have moderate to severe disease based on medication use. This study provides a greater understanding of the path from symptom onset to treatment and the heterogeneous presentation of patients with SLE who are treated in community practice in Australia. Key messages • Most published studies describing patients with SLE are derived from specialist lupus centres, typically in the hospital setting, therefore little is known about the characteristics of patients with SLE who are receiving routine care in community clinics. • The OPAL dataset is a large collection of clinical data from the electronic medical records of rheumatologists predominantly practising in private community clinics, which is where the majority (73-80%) of adult rheumatology services are conducted in Australia [1-3] . Since data from community care has not been widely available for SLE research, this study contributes important insight into this large and under-reported patient population. • To improve access to care and effective treatments, and reduce the burden of SLE in Australia, a greater understanding of the characteristics and unmet needs of patients with SLE managed in the community setting is required.

To analyze comparative treatment persistence for first-line baricitinib (BARI) versus first-line tumor necrosis factor inhibitor (TNFi) in patients with rheumatoid arthritis (RA) and for first-line BARI initiated as monotherapy versus first-line BARI initiated with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD).

Patients with RA who initiated BARI or TNFi as first-line biologic or targeted synthetic DMARD from October 1, 2015, to September 30, 2021, were identified in the OPAL data set. Drug survival times to 6, 12, and 24 months were analyzed using restricted mean survival time (RMST). Multiple imputation and inverse probability of treatment weighting were used to address missing data and nonrandom treatment assignment.

A total of 545 patients initiated first-line BARI, including 118 as monotherapy and 427 as csDMARD combination therapy. Three thousand five hundred patients initiated first-line TNFi. There was no difference in drug survival to 6 or 12 months for BARI compared with TNFi; differences in RMST were 0.02 months (95% CI: -0.08 to 0.013; P = 0.65) and 0.31 months (95% CI: -0.02 to 0.63; P = 0.06), respectively. Patients in the BARI group had 1.00 month (95% CI: 0.14 to 1.86; P = 0.02) longer drug survival to 24 months. There was no difference in drug survival for BARI monotherapy compared with combination therapy, with differences in RMST to 6, 12, and 24 months of -0.19 months (95% CI: -0.50 to 0.12; P = 0.12), -0.35 months (95% CI: -1.17 to 0.42; P = 0.41), and -0.56 months (95% CI: -2.66 to 1.54; P = 0.60), respectively.

In this comparative analysis, treatment persistence up to 24 months was significantly longer for first-line BARI compared with TNFi, but the effect size of 1.00 month is not clinically meaningful. There was no difference in persistence for BARI monotherapy versus combination therapy.

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.

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).

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.

Treatment with either ADA (40 mg every 14 days) or TOF (10 mg daily).

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.

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.

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.