Breakthrough COVID-19 After Tixagevimab/Cilgavimab Among Patients With Systemic Autoimmune Rheumatic Diseases

Abstract

ObjectiveTo determine the incidence and baseline factors associated with breakthrough COVID-19 after pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs).MethodsWe performed a retrospective cohort study among patients with SARDs who received tixagevimab/cilgavimab between January 2, 2022 and November 16, 2022. The primary outcome was breakthrough COVID-19 after tixagevimab/cilgavimab. We performed multivariable Cox regression models adjusted for baseline factors to identify risk factors for breakthrough COVID-19.ResultsWe identified 444 SARD patients who received tixagevimab/cilgavimab (mean age 62.0 years, 78.2% female). There were 83 (18.7%) breakthrough COVID-19 cases (incidence rate 31.5 per 1000 person-months [95% CI 24.7 - 38.2]), 7 (1.6%) hospitalizations and 1 (0.2%) death. Older age was inversely associated with breakthrough COVID-19 (adjusted hazard ratio [aHR] 0.86 per 10 years, 95% CI 0.75 - 0.99). Higher baseline spike antibody levels were associated with lower risk of breakthrough COVID-19 (aHR 0.42, 95% CI 0.18 - 0.99 for spike antibody levels >200 vs. <0.4 units). CD20 inhibitor users had a similar risk of breakthrough COVID-19 (aHR 1.05, 95% CI 0.44 - 2.49) compared to conventional synthetic DMARD users.ConclusionWe found that SARD patients had frequent breakthrough COVID-19, but the proportion experiencing severe COVID-19 was low. DMARD type, including CD20 inhibitors, did not significantly affect risk of breakthrough COVID-19. Evidence of prior humoral immunity was protective against breakthrough infection, highlighting the continued need for a multimodal approach to prevent severe COVID-19 as novel PrEP therapies are being developed.

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“…Similarly, in a retrospective cohort study of 400 rituximab (RTX)-treated patients in the UK, Yusof et al reported that whereas one-third of the cohort experienced breakthrough COVID-19, only a small proportion of patients experienced severe COVID-19. 8 These findings in the current Kawano et al study 7 and the recent Yusof et al 8 study are in stark contrast to those of numerous other studies throughout the pandemic that demonstrated a strong association between severe COVID-19 and B cell-depleting therapies, throughout all periods of the pandemic. 5 The reasons for these varying outcomes in terms of risk of severe COVID-19 in patients with B cell depletion remain unclear.…”

“…In this issue of The Journal of Rheumatology, Kawano et al report outcomes of breakthrough COVID-19 in patients with systemic rheumatic disease after receipt of tixagevimab/ cilgavimab and are the first to report this experience over nearly the entire approval period of the product, collecting cases through November 2022. 7 Out of 444 patients, almost one-fifth experienced breakthrough COVID-19 over 2637.6 person-months of follow-up with mostly favorable outcomes. Only 7 patients were hospitalized and 1 died.…”

“…Overall, MELODY found that having small-vessel vasculitis was the leading associated disorder among all conditions for having a nonresponse to 3 or more vaccines (49%). 9 Given that Kawano et al 7 and Yusof et al 8 both examined a predominantly RA population receiving B cell-depleting agents, with only a minority with underlying small-vessel vasculitis, the diagnosis may be an important contributing factor to the welcome but surprisingly favorable outcomes of COVID-19 in these investigations.…”