A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus.

OBJECTIVE: To explore long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE) who completed a Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP) trial and enrolled in the placebo-controlled 3-year long-term extension (LTE) study (ClinicalTrials.gov identifier: NCT02794285). METHODS: In the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks. Primary comparisons in the LTE study were between patients who received anifrolumab 300 mg or placebo throughout the TULIP and LTE studies. For rare safety events, comparisons included patients who received any anifrolumab dose during TULIP or LTE. When exposure differed, exposure-adjusted incidence rates (EAIRs) per 100 patient-years were calculated. RESULTS: In the LTE study, EAIRs of serious adverse events (SAEs) were 8.5 with anifrolumab compared with 11.2 with placebo; likewise, EAIRs of AEs leading to treatment discontinuation were 2.5 versus 3.2, respectively. EAIRs of non-opportunistic serious infections were comparable between groups (3.7 with anifrolumab versus 3.6 with placebo). Exposure-adjusted event rates of COVID-related AEs, including asymptomatic infections, were 15.5 with anifrolumab compared with 9.8 with placebo. No COVID-related AEs occurred in fully vaccinated individuals. EAIRs of malignancy and major acute cardiovascular events were low and comparable between groups. Anifrolumab was associated with lower cumulative glucocorticoid use and greater mean improvement in the SLE Disease Activity Index 2000, compared with placebo. CONCLUSION: This LTE study represents the longest placebo-controlled clinical trial performed in SLE to date. No new safety findings were identified in the LTE study, supporting the favorable benefit-risk profile of anifrolumab for patients with moderate-to-severe SLE receiving standard therapy.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

The role of antirheumatics in patients with COVID-19.

The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.