The emergence of de novo and relapsing anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following coronavirus disease 2019 (COVID-19) vaccination [1] in the midst of an unprecedented rapid global vaccination drive against COVID-19 is reminiscent of that reported after influenza vaccination [2]. A recent pharmacoepidemiological study of drug-associated AAV reported in the World Health Organization pharmacovigilance database between 2006 and 2020 found that influenza vaccination was one of the 15 drugs with disproportionate reporting for AAV [2].
However, earlier studies had noted that among prevalent AAV, disease activity scores did not change significantly after influenza vaccination, and flares temporally related to vaccination were infrequent [3]. A systematic review (PROSPERO registration number CRD42020181315) of the Cochrane Central Register of Controlled Trials, PubMed, Embase, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov up to 25 December 2021 noted that influenza vaccination safety was reported by five studies (422 patients) and was generally safe in AAV (Table 1) [4–8]. Conversely, influenza infection risk, morbidity and mortality are significantly amplified in autoimmune disease and immunosuppression [9], thus lending support for influenza vaccination in prevalent AAV and other autoimmune conditions [3].
Table 1.
Studies evaluating safety of influenza vaccine in ANCA-associated vasculitis
| Safety outcomes | ||||||
|---|---|---|---|---|---|---|
| Study | Study design | Participantsa | Follow-up, months | Relapse, n (%) | Disease activity | ANCA titer |
| Holvast et al. 2009 [4] | RCT | 49 | 1 | 1 (2.0) | NSC | NSC |
| 3–4 | 0 | NSC | NSC | |||
| Jeffs et al. 2015 [5] | RCT | 24 | 1 | 0 | NSC | NSC |
| 6 | 1 (4.2) | NSC | NSC | |||
| Saad et al. 2011 [6] | PC | 26 | 0.75 | NR | NR | NR |
| Stassen et al. 2008 [7] | RC | 156 | 12 | 3.4b | NR | NR |
| Zycinska et al. 2007 [8] | PC | 35 | 1 | 0 | NR | NR |
aParticipants who received influenza vaccination.
bPer 100 patients at risk.
ANCA, anti-neutrophil cytoplasmic antibody; RCT, randomized controlled trial; NR, not reported; NSC, not significantly changed; PC, prospective cohort; RC, retrospective cohort.
Since COVID-19 vaccine trial safety data in AAV are lacking as most trials have excluded immunosuppressed patients, a future pharmacoepidemiological study that includes emerging data such as that reported by Fillon et al. [1] may provide insights into the role of COVID-19 vaccines in de novo and relapsing AAV. In the meantime, the benefit of vaccinations for preventable infections such as influenza and COVID-19 with elevated infection-related mortality in immunosuppression likely outweighs the possibility of a disease flare. Increased physician and patient awareness and surveillance postvaccination may be considered in patients with immune-mediated kidney disease, including AAV [10].
Contributor Information
Jackie Sim, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tung Lin Lee, Department of Renal Medicine, Singapore General Hospital, Singapore.
Cynthia Ciwei Lim, Department of Renal Medicine, Singapore General Hospital, Singapore.
CONFLICT OF INTEREST STATEMENT
This article has not been published previously in whole or part. All authors declare no potential conflict of interest.
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