ABSTRACT
BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.
ABSTRACT
Background: Vaccination against SARS-CoV-2 has shown efficacy and safety in patients with chronic infammatory rheumatic disease, similar to the general population. However, in patients treated with rituximab (RTX) it is known that usually have a lower vaccination response rate (1-2), and recent studies suggest that it also happens with the new SARS-CoV 2 vaccine (3), which entails an increased risk of hospitalization and mortality in this specifc group of patients. Objectives: To describe humoral immune response to SARS-CoV-2 vaccine in rituximab-treated patients after one and six months from the vaccination, and study if there is any other factor associated with a lower response rate. Methods: Prospective analysis of a cohort of patients treated with RTX who received the SARS-CoV-2 vaccine between the months of April and October 2021. Demographic and medical data were collected through electronic medical records. Blood tests and serologies with levels of antibodies against SARS-CoV-2 were performed one and six months after having received the vaccine against SARS-CoV-2. The administration of a booster dose of the vaccine was recorded. A descriptive and statistical analysis of the data was carried out using the SPSS program. Results: From a cohort of 41 patients, of whom 81,4% were women with a mean age of 56 (13,4 SD) years, vaccine response rate was only 36,7% after a 6-month follow-up. The 88,4% of them received a booster dose of the vaccine, but this failed to produce a vaccine response in any of the patients who had not developed it with the previous ones. One patient became infected after receiving one dose of the vaccine and failed to develop a serological response either. Hypogammaglobulinemia was associated with a statistically signifcant lower probability of vaccine response (p=0,04). A trend of lower vaccination response rate was observed in patients who had received the last cycle of RTX in the 6 months prior to vaccination (p=0,058). In addition, the antibody levels developed one month after vaccination were statistically signifcantly correlated with the time between the last RTX cycle and vaccination (p=0,014) and also with CD19 B cells levels prior to vaccination (p<0,001);however, there was no correlation with the antibody levels detected at the 6-months serology. No statistically signifcant differences were found in relation to the number of previous cycles of RTX, concomitant treatment with synthetic disease-modifying drugs (DMARDs) or corticosteroids. Conclusion: In our sample, after a 6-month follow-up only 36,9% achieved a vaccine response against SARS-CoV-2, which did not improve despite the administration of a booster dose. Hypogammaglobulinemia, the time between the last RTX cycle and vaccination (at least 6 months), and previous CD19 B cells levels signifcantly influenced in the development of a humoral response to the vaccine.