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07-01-2022 | COVID-19 | News

Rituximab and COVID-19 vaccination: Timing may be key for antibody response

Author: Claire Barnard


medwireNews: Findings from two studies suggest that among rituximab-treated patients, those with a longer time since their last infusion may be more likely to have an antibody response to vaccines against SARS-CoV-2.

For the first study, Xavier Mariette (Hôpital Bicêtre, Paris, France) and colleagues evaluated data from 24 rituximab-treated patients with immune-mediated inflammatory diseases (IMIDs), 35 patients on other immunosuppressants for IMIDs, and 26 age- and sex-matched healthy controls who received two doses of the Pfizer–BioNTech (BNT162b2) vaccine. The most common IMID diagnosis was rheumatoid arthritis (RA; 44%), followed by Sjögren’s syndrome (25%).

Overall, average levels of immunoglobulin (Ig)G antibodies against the SARS-CoV-2 spike protein at 1 month after the second vaccine dose were significantly lower among rituximab-treated patients than those on other immunosuppressants or healthy controls, at 69 versus 180 and 235 units/mL, respectively.

When response to vaccination was defined as anti-spike antibody levels of above 50 units/mL – the threshold at which 97% of participants had neutralizing antibody levels of at least 24 IU/mL – just 29.2% of rituximab-treated patients responded, compared with 80.0% of those on other immunosuppressants and 92.3% of healthy controls.

Mariette and team say that among rituximab-treated patients, those with an antibody response to vaccination had a significantly longer time since their last rituximab infusion than nonresponders, at a mean of 233 versus 106 days.

Moreover, “[n]o patient with an infusion in the last 6 months responded,” they report in Arthritis & Rheumatology.

In accordance with these findings, the authors of the second study, Ingrid Jyssum (Diakonhjemmet Hospital, Oslo, Norway) and colleagues, also demonstrated an association between time since the last rituximab infusion and serologic response to vaccination.

In the Nor-vaC study, 21.8% of 87 rituximab-treated patients with RA had a serologic response (anti-spike antibody concentration ≥70 units/mL) at a median of 16 days after their second dose of the Pfizer–BioNTech, Moderna (mRNA-1273), or Oxford–AstraZeneca (ChAdOx1 nCoV-2019) vaccine, compared with 98.4% of 1114 healthy controls, a significant difference.

Among the RA patients, the median time from the last rituximab infusion was 267 days for responders, decreasing to 137 days for those with a weak response (anti-spike antibody concentration 5–69 units/mL), and 107 days for nonresponders (<5 units/mL). Multivariable analysis demonstrated that longer time since rituximab infusion was significantly associated with vaccine response (odds ratio [OR]=2.97 for each additional 100 days), as was receipt of the Pfizer–BioNTech vaccine (OR=9.12 vs Moderna).

These findings suggest that “[f]or an optimal response, the interval between rituximab infusion and vaccination should be as long as possible, preferably at least 9 months,” write Jyssum et al in The Lancet Rheumatology.

In addition to their evaluations of serologic responses, the authors of both studies also assessed T cell-mediated responses to SARS-CoV-2 vaccines.

Mariette and colleagues found that functional CD4+ and CD8+ cellular responses were not significantly different among IMID patients treated with rituximab compared with those on other immunosuppressants or healthy controls, suggesting “the probable usefulness of vaccination in [rituximab]-treated patients even if they do not develop a humoral response.”

In Jyssum and team’s study, 53.0% of rituximab-treated RA patients had a CD4+ T-cell response after two vaccine doses and 74.0% had a CD8+ response. Patients who did not have a serologic response to two doses in this study were given a third vaccine dose; all 12 evaluated patients had CD4+ and CD8+ T-cell responses 3 weeks after the third dose, while just 16.3% had a serologic response.

These findings suggest that the third vaccine dose may enable “robust T-cell immunity in patients with rheumatoid arthritis treated with rituximab, potentially improving protection in this patient group,” write the authors. They note, however, that “[f]urther studies are needed to assess the clinical protection provided by a cellular response in the absence of anti-SARS-CoV-2 antibodies.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

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Arthritis Rheumatol 2021; doi:10.1002/art.42058
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00394-5