ABSTRACT
Introduction: Inflammatory cytokines are central to the pathogenesis of the systemic autoinflammatory diseases (SAID) and agents targeting these pathways have transformed the management of SAID. These same pathways are involved in the balance between viral clearance and hyperinflammation during infection and have therefore been areas of active research interest into COVID-19. As a result, among patients with SAID on biologics, there are legitimate concerns regarding the risk of COVID-19 infection and safety of vaccination, which are exacerbated by the scarcity of published data on the outcomes of COVID-19 infection and vaccination in these patients. Objectives: This study establishes the prevalence and outcomes of COVID-19 infection and early outcomes of vaccination among a cohort of 248 patients with SAID on biologics. Methods: Data were collected from the electronic medical records of 248 patients with SAID on biologics at a national centre up to 26/7/ 21. Patients were also surveyed using a web-based survey completed in clinic or remotely between 4/3/21 and 26/7/21. Results: No deaths were recorded in this cohort of 248 patients between 29/1/20 and 26/7/21. In line with national guidance, all patients in this cohort were advised that the diagnosis of SAID managed with single-line biologic therapy was not an indication for shielding and that they should continue their biologic therapy unless otherwise instructed by a medical professional. Survey responses were received from 195 patients (195/248, 78.6%). Biologic therapy was as follows: anakinra (129/195, 66.2%), canakinumab (55/195, 28.2%), tocilizumab (8/195, 4.1%), etanercept (3/195, 1.5%), adalimumab (co-prescribed with anakinra) (1/195, 0.5%). Among survey respondents, 32 cases of suspected COVID-19 infection were reported, of which 15 were confirmed on testing (15/195, 7.7%). Two patients on anakinra were hospitalised due to dehydration. No patient required supplemental oxygen, mechanical ventilation or intensive care admission. Biologic therapy continued uninterrupted in all patients managed in the outpatient setting and was temporailty discontinued in the two hospitalised patients by the admitting team. Three patients with suspected or confirmed COVID-19 infection reported new symptoms that persisted for more than twelve weeks. 164/195 (84.1%) respondents had received the first vaccine dose and 79/195 (40.5%) had received two doses. 162/164 (98.8%) patients continued biologic therapy uninterrupted around the time of vaccination. Of the 243 vaccine doses administered, 138 (56.8%) were the Oxford Astra-Zeneca vaccine and 105 (43.2%) were the Pfizer-BioNTech vaccine. Following vaccination, no serious adverse events were reported and no patient required hospital admission. Side effects were reported following 130/243 (53.5%) doses and symptoms reported by patients to be in keeping with a flare of the underlying SAID were reported following 40/243 (16.5%). Side effects had fully resolved by 72 hours following 92.2% of doses (224/243). No cases of COVID-19 were reported following administration of both vaccine doses and only one early case was reported after the first dose, with symptom onset within five days of vaccine administration. Median follow up following vaccination was 10.5 weeks following the first dose and 6.0 weeks following the second. Conclusion: This study shows COVID-19 infection rates broadly in line with that of the UK general population among patients with SAID on biologics and demonstrates no significant concerns regarding outcomes of infection in these patients. We also present the largest series of patients with SAID or on IL-1/6 biologics to have received an adenoviral vector or mRNA vaccine and observe no significant early safety concerns. Whilst longer follow-up is needed to establish the efficacy of vaccination in these patients, these findings will support patients and their clinicians to make informed decisions around continuation of biologic therapy and vaccination during the ongoing COVID-19 pandemic.