Citations

Abstract Objectives We investigated coronavirus disease 2019 (COVID-19) vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares and AID-related treatment modifications were analysed upon diagnosis of AID vs healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. Results Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, P = 0.01; minor AE 40% vs 25.9%, P = 0.03; major AE 17.5% vs 4.6%, P < 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination disease flares were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a disease flare were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. Conclusion This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and for the fetus by passive immunization appear to outweigh potential risks.

Introduction: Rare cardiac complications of COVID-19 and COVID-19 mRNA vaccination include pericarditis and myocarditis. Patients with recurrent pericarditis may be at increased risk of triggered recurrence. The known efficacy of the interleukin (IL)-1 antagonist rilonacept in treating and preventing recurrence could inform COVID-19 disease and vaccination management. Methods: The Phase 3 trial RHAPSODY was a global, double-blind, placebo-controlled, randomized-withdrawal study. A long-term extension (LTE) enabled up to 24 months further open-label treatment from May 2020 until June 2022. Concomitant vaccination data and adverse events, including COVID-19, were collected. Results: No COVID-19 cases were reported during the run-in and randomized withdrawal periods (n=86). As of the 6 May 2022 data cutoff, a COVID-19 AE was reported in 19% (14/74) of LTE subjects, of whom 12 were on rilonacept: 5 of 44 fully-vaccinated (≥14 days beyond second serial dose) subjects (11.4%) and 9 of 30 unvaccinated or partially-vaccinated subjects (30.0%). Of the fully-vaccinated subjects, 1 case occurred ~11 months post primary vaccination cycle (no booster). COVID-19 severity was mild (n= 11), moderate (n=2), or severe (n=1). All cases resolved except the severe AE complicated by comorbidities; the subject discontinued. Of 12 subjects receiving rilonacept at the time of COVID-19 diagnosis, 10 maintained dosing with rilonacept, 1 interrupted rilonacept for ~4 weeks, and 1 discontinued rilonacept permanently; none experienced a pericarditis recurrence (PR) after the AE. The remaining 2 subjects had previously interrupted rilonacept for off-treatment observation: one had a PR >4.5 months after suspending rilonacept and 18 days after COVID-19 resolution; no PR in the other (>6 months). There were no PR AEs associated with COVID-19 vaccination (all subjects were receiving rilonacept). Conclusions: In patients on rilonacept in this study, although numbers are small, vaccination reduced COVID-19 events, pericarditis recurrence was not increased by vaccination or disease, and no pericarditis recurrences occurred during rilonacept treatment. One pericarditis recurrence occurred remotely after rilonacept suspension in the peri-COVID-19 period.

Introduction: Rilonacept reduced pericarditis recurrence in the phase 3 trial RHAPSODY. The long-term extension (LTE) enabled further insights into efficacy, safety, and clinical decision making. Methods: The RHAPSODY run-in (RI) and randomized-withdrawal periods were followed by an LTE that enabled open-label rilonacept treatment up to 24 additional months. A decision at 18 months after the most recent recurrence was based on clinical status at investigator discretion: 1) continue rilonacept on-study, 2) suspend rilonacept for observation or 3) discontinue from the LTE without observation. Endpoints included recurrence and quality of life. Results: In May 2020, 74 of 75 eligible subjects continued to LTE; US subjects (n=45) switched to commercial therapy or discontinued in April 2021 (treatment duration from RI baseline [median; maximum] 18; 27 months). Non-US subjects (n=29) completed the LTE in June 2022 (treatment duration from RI baseline [median; maximum] 27; 33 months). Concomitant oral medications during LTE: 22% NSAIDS, 20% colchicine, 0% corticosteroids, 43% none. Inflammation signs (CRP), RP symptoms (PGIPS), and recurrences were low on-treatment. Before the 18-month decision (n=74), there were 3 investigator-assessed recurrences (0.04 per patient-year). At the 18-month decision (n=52), 64% (n=33) continued rilonacept on-study, 15% (n=8) suspended rilonacept for observation, and 21% (n=11) discontinued the study without observation, of whom 7 switched to commercial rilonacept. There was a 75% recurrence rate (n=6/8) in the off-treatment observation group (median time to event 11.8 [3.7, Not-Estimable (NE)] weeks) but only 1 recurrence in subjects on rilonacept (time to event NE [too few events]) associated with a 4-week interruption; HR 0.018, p<0.0001; Fig 1. Conclusions: Continued rilonacept treatment resulted in continued treatment response, whereas treatment suspension at 18 months may be associated with pericarditis recurrence.

Abstract Objectives We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. Methods A cross-sectional ancillary analysis of the ‘COVID-19 vaccination in auto-immune disease’ (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. Results Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. Conclusion We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.

Abstract Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with &gt;7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. Results Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7–235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P &lt; 0.001) were associated with disparity between self-reported and IS-denoted flares. Conclusion A diagnosis of IIMs confers an equal risk of flares in the post–COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P &lt; 0.001) and autoimmune disease multimorbidity (AIDm) (P &lt; 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P &lt; 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.