Rituximab Frequency Could Influence Rheumatic Patient Response to COVID-19 Vaccines

Victoria Furer, MD

Humoral response to the Pfizer-BioNTech COVID-19 vaccine BNT162b2 among patients with autoimmune inflammatory rheumatic diseases may be harmed by their use of rituximab, according to a new study.

In new data presented at the American College of Rheumatology (ACR) 2021 Convergence this week, a team of Israel-based investigators observed that the monoclonal antibody commonly used in treatment of various rheumatic diseases was negatively associated impaired humoral response in adult patients administered the mRNA vaccine for COVID-19.

Rituximab is currently approved by the US Food and Drug Administration (FDA) to treat a litany of rheumatic and autoimmune diseases including rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyganiitis, and pemphigus vulgaris. Its potential impact on patient immunization against SARS-CoV-2, contrasted with its benefit for managing rheumatic and autoinflammatory disease, leads investigators to stress that COVID-19 vaccination timing needs to be “optimized” in at-risk patients.

Led by Victoria Furer, MD, of the Tel Aviv Sourasky Medical Center, investigators sought to identify what predictors are associated with lacking humoral response in patients treating their autoimmune inflammatory rheumatic diseases who have received the Pfizer-BioNTech COVID-19 vaccine. They conducted a sub-analysis of a prospective trial that investigated the immunogenicity of the 2-dose BNT162b2 regimen in adults treating autoimmune rheumatic disease with rituximab

Eligible patients for the trial included adults diagnosed with:

• Rheumatoid arthritis
• Systemic lupus erythematosus (SLE)
• Systemic vasculitis
• Inflammatory myositis

Furer and colleagues compared the rituximab-treated cohort to controls without rheumatic disease or patients not using immunosuppressants.

Investigators collected data on the serum immunoglobulin G (IgG) level of patients prior to the last administered course of rituximab, as well as post-vaccination serum IgG levels against SARS-CoV-2 spike (S1/S2) proteins 2-6 weeks after the second vaccine dose.

They defined seropositivity as IgG 315 binding antibody units (BAU)/ml, and predicted seropositive results in autoimmune rheumatic patients through a stepwise backward multiple logistic regression.

The trial population consisted of 98 patients and 122 controls, of which females were the majority in each (75.5% and 64.8%, respectively). Patients with autoinflammatory rheumatic disease were on average 12 years older than the mean control age (62.3 vs 50.8 years; P >.001), and 4 patients with a past history of lymphoma were identified.

Seropositivity rates among patients treated with rituximab were significantly lower (38.8%) than controls (100%; P <.0001), as were mean S1/S2 IgG levels (49.9 vs 218.4 BAU/ml, respectively; P <.0001).

Among seronegative and seropositive patients treated with rituximab, total courses of therapy differed significantly—as did IgG levels prior to the last course of rituximab and the interval between the last course of rituximab and COVID-19 vaccination.

Furer and colleagues additionally observed that patients with rheumatoid arthritis were associated with the greatest probability for COVID-19 vaccine response among the rituximab cohort, while patients specifically with ANCA-associated vasculitis were associated with an approximately 78% reduced chance of vaccine response (OR, 0.223; P = .059).

IgG levels in patients prior to their last course of rituximab and days between last rituximab course and COVID-19 vaccination were associated positively with seropositive response.

Investigators concluded that patients with autoinflammatory rheumatic disease who had no humoral response to COVID-19 vaccination with BNT162b2 had these consistent traits:

• A high exposure to rituximab over time
• Low IgG levels prior to their final course of therapy
• Short interval between last rituximab course and COVID-19 vaccination

“These data should guide the optimal timing of vaccination in patients treated with rituximab,” they wrote.

The study, ”Factors Associated with Reduced Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) Treated with Rituximab,” was presented at ACR 2021.