Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines.AimsTo fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine’s immunogenicity.MethodsHumoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls.ResultsPatients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines.ConclusionsPatients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.

Satisfaction and Adherence to Biological Treatment in Patients with Rheumatic Diseases

Background: Autoimmune inflammatory rheumatic diseases have long been treated by conventional disease-modifying anti-rheumatic drugs. Biological therapy is a new era in the treatment of rheumatic diseases, but satisfaction and adherence to it is still not well tested. Aim: To assess the satisfaction and adherence to biological treatment among patients with autoimmune inflammatory rheumatic diseases. Methods: A cross sectional study was conducted among 56 patients suffering from inflammatory rheumatic diseases using Morisky 8 questionnaire and Treatment Satisfaction Questionnaire for Medication (TSQM) over a period of one month Results: About 76.8% of the patients had medium adherence and the underlying cause of missing doses was the unavailability of the drugs. The mean satisfaction with biological treatment was 62.7±6.9. Patients who did not receive formal education had significantly higher satisfaction with the biological treatment than others 64.94±5.01 at a P value 0.04 (<0.05). Conclusion: Patients with inflammatory rheumatic diseases in our study showed medium adherence and satisfaction. Authorities in the medical field are providing great help to these patients in need of biological therapy, but ensuring the availability of all doses of the biological treatment regimen is still necessary. Patient, family and nurse education programs are also necessary to maximize adherence and satisfaction.

Organ Manifestation and Systematic Organ Screening at the Onset of Inflammatory Rheumatic Diseases

Background: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. Materials and Methods: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. Results: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. Conclusion: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Predictors of an Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab: A Multicenter Study

BackgroundTreatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral response. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX).MethodsWe analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls immunized with BNT162b2 mRNA vaccine participating in a multicenter vaccination study. Immunogenicity was defined by positive anti-SARS-CoV-2 S1/S2 IgG measured at 2 to 6 weeks after the second vaccine dose. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX patients (n=48) immunized with the BNT162b2 mRNA vaccine.Results AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from non-responders by lower number of RTX courses (median (range) 3 (1-10) vs 5 (1-15), p=0.007; lower cumulative RTX dose 6943.11±5975.74 vs 9780.95±7240.12 mg, p=0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78±576.28 vs. 884.33±302.31 mg/dL, p=0.002, and extended interval between RTX treatment and vaccination, 469.82±570.39 vs 162.08±160.12 days, p=0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046-0.96, p=0.044 and OR 0.189, 95% CI 0.036-0.987, p=0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, 63.3% positive and 88.9% negative predictive values.ConclusionsThe predicting calculator might guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.

Course and outcomes of COVID-19 in patients with immunoinflammatory rheumatic diseases: Preliminary data from the NIIR/APP-COVID-19 registry and literature review

The materials of the Russian NIIR/ARP-COVID-19 database, which included adult (over 18 years old) patients with immuno-inflammatory rheumatic diseases (IIRD) who underwent COVID-19 (coronavirus disease 2019), and a literature review concerning the course and outcomes of COVID-19 in patients with these diseases, are presented. From July 17, 2020 to April 23, 2021, 156 messages were received and analyzed. The study group was represented mainly by women (75%). The average age of patients was 52.0±14.8 years, of which 53 (33.9%) patients were aged 60 years and older. The most frequent clinical manifestations of COVID-19 were fever (62.2%), cough (40.4%), anosmia (37.8%), shortness of breath (33.3%). During the course of COVID-19, computed tomography of the chest organs was performed in 143 patients. When assessed on an “empirical” visual scale, stage 0 of lung lesion was observed in 49 (34.3%) patients, stage 1 in 40 (28%), stage 2 in 35 (24.5%), stage 3 in 19 (13.2%), stage 4 in 0. In the study group, a favorable outcome was observed in 137 (97.9%) patients. Fatal outcome was registered in 3 patients. The effect of COVID-19 on the course of IIRD was assessed in 131 patients: in 52 (39.7%) patients, the course of IIRD worsened, in 1 (0.8%) it improved, in 78 (59.5%) there was no effect. Literature data on the risk of infection with the SARS-CoV-2 virus, the course and outcomes of COVID-19 in rheumatic and musculoskeletal diseases are contradictory, which dictates the need to continue collecting data on the rheumatological problems of COVID-19 in the Russian patient population, taking into account international experience.

PolyMyalgia Rheumatica Treatment With Methotrexate in Optimal Dose in an Early Disease Phase (PMR MODE): Study Protocol for a Multicenter Double-blind Placebo Controlled Trial.

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder-, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe.The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5–10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing and dose of MTX in PMR remains unclear and therefore our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients. MethodsWe set up a double blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52. DiscussionNo relapsing PMR patients were chosen, since the the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exist. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects. Trial registrationDutch trial registration, NL8366 Registered on 2020-02-10