Flares in autoimmune rheumatic diseases in the post-COVID-19 vaccination period - A Cross-sequential study based on COVAD surveys

OBJECTIVE: Flares of autoimmune rheumatic disease (AIRDs) following COVID-19 vaccination are an outstanding 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 among 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 15165 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 (MHD) (p < 0.001), and autoimmune multimorbidity (AIDm) (p < 0.001).In regression analysis, the presence of AIDm (OR = 1.4;95%CI:1.1-1.7;p=0.003), MHD (OR = 1.7;95%CI:1.1-2.6;p=0.007), and Moderna vaccine (OR = 1.5;95%CI:1.09-2.2;p=0.014) recipients were predictors of flares. Mycophenolate (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 to before vaccination (OR = 1.3;95%CI:1.1-1.5;p<0.001).

CONCLUSION: Flares occur in nearly one in ten individuals with AIRDs after COVID vaccination, with people with comorbidities, especially AID multimorbidity, mental health disorders and use of the Moderna vaccine being particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.