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.
ABSTRACT
Background: Several studies have suggested that multiple sclerosis (MS) patients have low bone mineral density (LBMD) compared to healthy adults of same age. This fact, combined with the functional impairment of the disease, increases the risk of fractures. However, information about the prevalence and the risk factors of LBMD in Spanish patients with MS is still quite limited1-3. Objectives: To evaluate the prevalence of LBMD and low vitamin D in patients with MS from a unique center from the east of Spain, describing the clinical features of these patients. Methods: Type of study: observational, cross-sectional, descriptive. Patients with MS from a local cohort have been consecutively recruited for this study since Apr-2020. A cross-sectional visit which included a clinical interview, analytic test (blood and urine) and a dual-energy X-ray absorptiometry (DXA) was performed. We defined LBMD as T score ≤-1SD in postmenopausal women and men over 50 years and a Z score ≤-2SD in premenopausal women and men under 50 years. Low levels of vitamin D were defined as < 20ng/mL. A descriptive and associative analysis of these data was carried out using the SPSS software. Results: From a cohort of 288 MS patients, due to the COVID-19 pandemia, we have only been able to assess 60 patients, and only 48 out of them have undergone all the tests required. These were 30 women and 18 men, with a mean age of 49 (SD 11,6) years. The main type of MS was relapsing-remiting (77,1%) and 25% of them were not taking any maintenance treatment. Some of the classical factors related to a LBMD are shown in table a1. A 43,8% of the patients had a LBMD and 40,5% had low levels of vitamin D. Despite these results, as far as 89% of patients had never received any specific treatment, not even calcium and/or vitamin D supplementation. Furthermore, 13 patients (27,1%) must have received specific treatment, according to latest guidelines4, and only 4 of them (8,5%) were being adequately treated. Conclusion: These preliminary results show that almost half of the MS patients have LBMD and a low vitamin D, most of them without taking any specific treatment. Taking this in mind, it is necessary to integrate the early diagnosis of LBMDin MS patients, working together with neurologists, to prevent the appearance of fractures and protect the quality of life of these patients. An analysis of our whole cohort of MS patients will help us in correctly assessing the magnitude of this problem.
ABSTRACT
Background: Factors associated with the development of chronic heart failure (CHF) in systemic lupus erythematosus (SLE) have received little attention. On the other hand, recent data from the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection during the COVID19 pandemic have cast some doubts on its cardiological safety. Objectives: To identify factors associated to CHF in SLE. Methods: Retrospective cross-sectional study, including all patients with SLE (≥4 ACR-1997 criteria) recruited in RELESSER registry. The objectives and methodology of the registry have been described previously (1). CHF was defined according to the Charlson index item. Patients with CHF before diagnosis of SLE were excluded. Cumulative damage was measured with the SLICC/ ACR index, excluding cardiovascular (CV) items (mSDI). Multivariate analysis exploring factors associated with CHF was carried out. Results: 117 patients (3% of the entire cohort) with SLE and CHF and 3,506 controls with SLE without CHF were included. 90% were women. Disease duration: mean (SD), 120.2 (87.7) months. CHF appeared after a median (P25-P75) of 9.40 (4.2-18.3) years from SLE diagnosis. Patients with CHF were older (59.8 ± 18.2 vs. 46.2 ± 4.3). In the bivariate analysis, the association of CHF with greater severity [Katz severity index: median (IQR): 4 (3-5) vs. 2 (1-3)], damage [mSDI: 3 (2-4) vs 0 (0-1)], comorbidity [modified Charlson-excluding CV items: 4 (3-6) vs 1(1-3)] and both CV (37.5% vs 6.7%) and overall mortality (43.2% vs 4.7%) (p<0.0001 for all comparisons). Also, CHF patients were more refractory to SLE treatments (33.3% vs 24%, p=0.0377) and were more frequently hospitalised due SLE [median 3 (1-5) vs 1(0-2), p<0.0001]. The results of the multivariable model are depicted in table 1. Conclusion: -CHF is a rather late complication of SLE. -Patients with SLE and CHF have more severe SLE, with greater refractoriness to SLE treatments and higher overall mortality. -Treatment with antimalarials, as routinely used in SLE patients, is not only safe to heart, but even appears to have a cardioprotective effect. (Table Presented).