key: cord-0961681-bpk04kix
authors: Quartuccio, Luca; Treppo, Elena; Binutti, Marco; Del Frate, Giulia; De Vita, Salvatore
title: Timing of Rituximab and immunoglobulin level influence the risk of death for COVID-19 in ANCA-associated vasculitis
date: 2021-02-20
journal: Rheumatology (Oxford)
DOI: 10.1093/rheumatology/keab175
sha: f612236b0fe8197881182d00085d3451575f3daa
doc_id: 961681
cord_uid: bpk04kix

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Since RTX primarily interferes with the humoral response, some reports have already highlighted the risk of facilitating severe consequences in SARS-CoV-2 infection by RTX (1) (2) (3) (4) . The latest data coming from the COVID-19 Global Rheumatology Alliance (C19-GRA) physician-reported registry reported the strongest association of rituximab (RTX) with the worst outcomes in rheumatic patients getting SARS-CoV-2 infection (5) . Yet, patients carrying systemic vasculitis or systemic lupus erythematosus may be at higher risk of hospitalisation due to COVID-19 (6) . While the registry collected a large amount of clinical data, unfortunately, the C19-GRA physician-reported registry did not capture the exact timing of infection after RTX administration, the possible role of concurrent glucocorticoids and previous immunosuppression, and, finally, the level of baseline immunoglobulins.

RTX became a licenced therapy for remission induction of ANCA-associated vasculitis (AAV) in 2011, and it has been recently proposed even as a treatment option in remission maintenance (7). Importantly, RTX or cyclophosphamide are the drugs of choice as induction therapy in severe or lifethreatening AAV (7) . Recently, baseline low immunoglobulin levels have been listed among the main risk factors for serious infections under RTX in AAV (8) .

From February to December 2020, we evaluated 100 patients (53 females; 47 males) with the diagnosis of granulomatosis with polyangiitis (GPA) (56%), granulomatosis eosinophilic with polyangiitis (EGPA) (31%), or microscopic polyangiitis (MPA) (13%). SARS-CoV-2 infection was diagnosed in 2 cases (2%) by nose-pharyngeal (NP) swab. Notably the incidence of SARS-CoV-2 infection in the general population of the same geographical area was 6.3% (29680 cases/466700 inhabitants). In that period, RTX was employed as maintenance in 15 patients with AAV. Low doses of glucocorticoids were concomitantly taking by 6 out of 15 (≤ 5 mg/day of prednisone equivalent).

Both the two cases of SARS-CoV-2 infection were undergoing RTX as remission maintenance. Timing of RTX and IgG levels were quite different between the two cases (Figure 1 ), and may have conditioned the final outcome greatly. SARS-CoV-2 viral load was not available for these cases, but it could be of importance for the outcome of patients undergoing RTX who develop COVID-19.

Importantly, while AAV patients do not appear at higher risk of COVID-19 than the general population, those patients undergoing anti-CD20 therapy could be at higher risk of developing critically ill COVID-19. Thus, patients needing RTX require prioritization for SARS-CoV-2 vaccination.

There are no competing interests for any author 

There are no funders to report for this submission

The study was conducted in accordance with the ethical principles of the Helsinki Declaration, and approved by the local Ethics Committee (ID number CEUR-2020-Os-129). 54x30mm (300 x 300 DPI)

Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature

The impact of COVID-19 pandemic on patients with ANCA associated vasculitis

Rituximab for granulomatosis with polyangiitis in the pandemic of covid-19: lessons from a case with severe pneumonia

Increased risk for severe COVID-19 in patients with inflammatory rheumatic diseases treated with rituximab

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID

Global Rheumatology Alliance physician-reported registry

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry

BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis

Long-term maintenance rituximab for ANCA-associated vasculitis: relapse and infection prediction models. Rheumatology (Oxford)

Legend to the Figure

Figure 1. Summary of the course of COVID-19 in the two AAV cases. ARDS, acute respiratory distress syndrome

All data relevant to the study are included in the article. No additional data are available.

Immunoglobulins, timing and SARS-CoV-2 vaccination should be carefully considered during maintenance with RTX in AAV