Impact of rituximab on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with autoimmune diseases

E Oliosi; A Flahault; C Charre; D Veyer; A Combier; E Lafont; A Karras; L Mouthon; J Avouac; B Terrier; J Hadjadj

doi:10.1007/s10067-023-06638-0

Impact of rituximab on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with autoimmune diseases

Clin Rheumatol. 2023 Sep;42(9):2485-2490. doi: 10.1007/s10067-023-06638-0. Epub 2023 May 27.

Authors

E Oliosi^{1

2}, A Flahault³, C Charre⁴, D Veyer⁵, A Combier⁶, E Lafont⁷, A Karras³, L Mouthon⁸, J Avouac⁶, B Terrier⁸, J Hadjadj⁸

Affiliations

¹ Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, Hôpital Cochin, Université de Paris Cité, 75014, Paris, France. emma.oliosi@aphp.fr.
² Service de Maladies infectieuses et tropicales, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France. emma.oliosi@aphp.fr.
³ Department of Nephrology, AP-HP, Hôpital Européen Georges Pompidou, 75015, Paris, France.
⁴ Department of Virology, AP-HP, Hôpital Cochin, 75014, Paris, France.
⁵ Department of Virology, AP-HP, Hôpital Européen Georges Pompidou, 75015, Paris, France.
⁶ Department of Rheumatology, AP-HP, Hôpital Cochin, 75014, Paris, France.
⁷ Department of Internal Medicine, AP-HP, Hôpital Européen Georges Pompidou, 75015, Paris, France.
⁸ Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, Hôpital Cochin, Université de Paris Cité, 75014, Paris, France.

Abstract

SARS-CoV-2 infection is more severe in patients undergoing rituximab (RTX) treatment. Humoral response to vaccination is severely impaired in patients already treated with RTX, but data on antibody persistence in patients initiating RTX are lacking. We evaluated the impact of RTX initiation on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with immune-mediated inflammatory diseases. We performed a retrospective, multicenter study evaluating the evolution of anti-spike antibodies and breakthrough infections after initiation of RTX in previously vaccinated patients with protective levels of anti-SARS-CoV-2 antibodies. Threshold for anti-S antibodies positivity and protection were 30 and 264 BAU/mL, respectively. We included 31 previously vaccinated patients initiating RTX (21 female, median age 57 years). At first RTX infusion, 12 (39%) patients had received 2 doses of vaccine, 15 (48%) had received 3 doses, and 4 (13%) had received 4 doses. The most frequent underlying diseases were ANCA-associated vasculitis (29%) and rheumatoid arthritis (23%). Median anti-S antibody titers at RTX initiation, 3 months, and 6 months were 1620 (589-2080), 1055 (467-2080), and 407 (186-659) BAU/mL, respectively. Overall, antibody titers waned by almost two-fold at 3 months and four-fold at 6 months. Median antibody titers were significantly higher in patients who received ≥3 doses compared to those who received only 2 doses. Three patients developed SARS-CoV-2 infection without any severe symptom. Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after RTX initiation similarly to general population. Specific monitoring is useful to anticipate prophylactic strategies. Key Points • Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after rituximab initiation similarly to the general population. • The number of dose of vaccine before rituximab initiation is associated with higher antibody titers at month 3. • Monitoring antibody levels is mandatory to initiate prophylactic strategies in this population.

Keywords: Biological therapy; Rituximab; SARS-CoV-2; Vaccines.

Publication types

Multicenter Study

MeSH terms

Antibodies, Viral
Autoimmune Diseases* / drug therapy
COVID-19 Vaccines
COVID-19* / prevention & control
Female
Humans
Middle Aged
Retrospective Studies
Rituximab / therapeutic use
SARS-CoV-2
Vaccination

Substances

Rituximab
COVID-19 Vaccines
Antibodies, Viral