Rituximab Linked to Worse COVID-19 Vaccine Response than Immunosuppressants

Samuel Bitoun, MD, PhD

Rituximab-treated patients with autoimmune disorders may be discriminately burdened by lacking response to COVID-19 mRNA vaccination, according to an American College of Rheumatology (ACR) 2021 Convergence study which complemented similar research presented at the annual meeting.

The findings from a team of France-based investigators contribute to a more specified understanding of minimal neutralizing antibody response observed in patients being treated with immunosuppressants—namely, showing how rituximab may be particularly reduced the benefit of mRNA vaccines in treated patients.

Led by Samuel Bitoun, MD, PhD, a rheumatologist at the Bicetre Hospital in Paris, investigators sought to compare the response to available COVID-19 mRNA vaccines in patients with autoimmune disease treated with either rituximab or immunosuppressants, versus health controls.

As they noted, though the pandemic is beginning to come under control with “massive vaccination” efforts, there has been burden nonetheless in assuring high-risk immunosuppressed patients are protected; they cited data showing patients with autoimmune disease treated with rituximab face a 3-fold increased risk of COVID-19 death than the general public (HR, 4.04; 95% CI, 2.32 – 7.03).

“Despite the tremendous efficacy of novel mRNA vaccines, some immunocompromised patients seem not to respond at the same level compared to healthy controls to these vaccines when anti-spike antibodies are considered,” investigators wrote.

Bitoun and colleagues observed samples of autoimmune disorder patients and healthy controls, all of whom were vaccinated with Pfizer-BioNTech’s BNT162b2, at 28 and 56 days after initial vaccination with the 2-dose regimen.

Patients were stratified by those who received rituximab for ≤1 year, and those who received any other immunosuppressant therapy. Investigators conducted serologic vaccine response and neutralization assessments; a threshold of ≥50 anti-Spike immunoglobulin G (IgG) was defined as vaccine response. Any patients with detectable anti-nucleocapsid levels at any point were excluded from assessment.

Investigators included 57 autoimmune disease patients and 28 healthy controls. Among patients, 24 were receiving rituximab and 33 were receiving other immunosuppressants. At day 28, healthy controls reported a median anti-Spike IgG level of 46.7, versus a median 0.4 in patients on rituximab and 4.5 in patients on immunosuppressants. Response rates were similarly worse in patients treated with rituximab (29.2%) versus patients on immunosuppressants (79.4%) and healthy controls (92.2%).

Investigators observed an association between lesser time to last rituximab infusion and non-response to mRNA vaccination; no patients to receive rituximab in the previous 6 months had responded to BNT162b2.

Such findings were consistent with other data presented this week at ACR 2021, in which Israel investigators reported that rituximab frequency and recent use were positively correlated with minimal immune response to the mRNA vaccine.

Indeed, Bitoun and colleagues concluded that the lower initial vaccine response observed in both patients on rituximab and other immunosuppressants was only continued in rituximab patients after 1 month post-vaccination.

“Given the low frequency of patients on rituximab having a humoral response, it will be key to assess if these patients will have or not a cellular response,” they wrote.

The study, “Rituximab Treatment Dramatically Reduces Neutralizing Humoral Response to mRNA SARS-COV-2 Vaccines in Patients with Autoimmune Diseases,” was presented at ACR 2021.