Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.

Objectives: To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients. Methods: This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions. Results: There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1-25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08-0.26). Conclusions: SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.

Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases.

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients.

Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a long-term, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients.

[Vaccine prevention in patients with rheumatic diseases]. / Prévention vaccinale chez les patients avec des maladies rhumatismales.

Patients with inflammatory rheumatologic diseases are at increased risk for infectious complications, including SARS-CoV-2, which represent one of the leading causes of death in this population. This risk is due to both the numerous comorbidities of this patient's group and the immunosuppressive therapies they receive. Vaccination reduces the incidence, complications, and mortality from infections. For patients receiving immunosuppressors, exacerbation of underlying diseases is rarely observed after immunization and only live-attenuated vaccines are contraindicated. A vaccination history and updated vaccination plan should be part of the clinical follow-up of patients with inflammatory rheumatism.

Les patients souffrant de maladies rhumatologiques inflammatoires sont plus à risque de complications infectieuses, y compris avec le SARS-CoV-2, qui représentent l'une des premières causes de mortalité dans cette population. Ce risque est attribuable à la fois aux nombreuses comorbidités de ces patients et aux thérapies immunosuppressives qu'ils reçoivent. La vaccination diminue l'incidence, les complications et la mortalité dues aux infections. Pour les patients recevant des immunosuppresseurs, une exacerbation significative des maladies sous-jacentes n'est qu'exception nellement observée après vaccination et seuls les vaccins vivants atténués sont en principe contre-indiqués. Une anamnèse vaccinale et une mise à jour du plan vaccinal doivent faire partie du suivi clinique de patients souffrant d'un rhumatisme inflammatoire.

Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab.

IMPORTANCE: The SARS-CoV-2 variant B.1.1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. OBJECTIVE: To determine T-cell responses to the Omicron spike protein in anti-CD20-treated patients with multiple sclerosis (MS) before and after a third messenger RNA COVID-19 vaccination. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study conducted from March 2021 to November 2021 at the University Hospital Geneva, adults with MS receiving anti-CD20 treatment (ocrelizumab) were identified by their treating neurologists and enrolled in the study. A total of 20 patients received their third dose of messenger RNA COVID-19 vaccine and were included in this analysis. INTERVENTIONS: Blood sampling before and 1 month after the third vaccine dose. MAIN OUTCOMES AND MEASURES: Quantification of CD4 and CD8 (cytotoxic) T cells specific for the SARS-CoV-2 spike proteins of the vaccine strain as well as the Delta and Omicron variants, comparing frequencies before and after the third vaccine dose. RESULTS: Of 20 included patients, 11 (55%) were male, and the median (IQR) age was 45.8 (37.8-53.3) years. Spike-specific CD4 and CD8 T-cell memory against all variants were maintained in 9 to 12 patients 6 months after their second vaccination, albeit at lower median frequencies against the Delta and Omicron variants compared with the vaccine strain (CD8 T cells: Delta, 83.0%; 95% CI, 73.6-114.5; Omicron, 78.9%; 95% CI, 59.4-100.0; CD4 T cells: Delta, 72.2%; 95% CI, 67.4-90.5; Omicron, 62.5%; 95% CI, 51.0-89.0). A third dose enhanced the number of responders to all variants (11 to 15 patients) and significantly increased CD8 T-cell responses, but the frequencies of Omicron-specific CD8 T cells remained 71.1% (95% CI, 41.6-96.2) of the responses specific to the vaccine strain. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with MS treated with ocrelizumab, there were robust T-cell responses recognizing spike proteins from the Delta and Omicron variants, suggesting that COVID-19 vaccination in patients taking B-cell-depleting drugs may protect them against serious complications from COVID-19 infection. T-cell response rates increased after the third dose, demonstrating the importance of a booster dose for this population.

[Rheumatology: 2021 update]. / Rhumatologie.

In rheumatology, this year has seen an expansion of knowledge about the effects of COVID and the vaccine response in patients with autoimmune diseases, but also a re-examination of the usual doses of glucocorticoids in vasculitides and new treatments strategies for diseases such as systemic lupus erythematosus, spondylarthritis and rheumatoid arthritis. New criteria for imaging assessment in spondylarthritis and new management guidelines for patients with low back pain have also been proposed.

En rhumatologie, dans les nouveautés que nous avons choisi de mettre en avant, cette année a vu l'élargissement des connaissances sur le Covid et la réponse vaccinale chez les patients avec maladies autoimmunes, la remise en question des doses habituelles des corticostéroïdes dans les vascularites et la possibilité de nouveaux traitements ou stratégies de prise en charge, dans le lupus érythémateux systémique, les spondylarthrites et la polyarthrite rhumatoïde. De nouveaux critères pour l'évaluation de l'imagerie des spondylarthrites ont aussi été proposés et des précisions quant au type de prise en charge nécessaire pour les patients lombalgiques ont également été apportées.

Incidence of COVID-19 in patients treated with infliximab compared with patients treated with rituximab.

OBJECTIVE: To determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors. METHODS: We included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group. RESULTS: 190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher's exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry. CONCLUSION: While the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.

Robust T-Cell Responses in Anti-CD20-Treated Patients Following COVID-19 Vaccination: A Prospective Cohort Study.

BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.

EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.

BACKGROUND: Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA). METHODS: An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1-10) for each PTC. RESULTS: Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants' knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach. CONCLUSION: These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

Impact of the COVID-19 pandemic on the disease course of patients with inflammatory rheumatic diseases: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To investigate whether the transient reduction in rheumatology services imposed by virus containment measures during the COVID-19 pandemic was associated with disease worsening in axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA). METHODS: Patient-reported disease activity assessed during face-to-face visits and/or via a smartphone application were compared between three periods of each 2 months duration (before, during and after the COVID-19-wave) from January to June 2020 in 666 patients with axSpA, RA and PsA in the Swiss Clinical Quality Management cohort. RESULTS: The number of consultations dropped by 52%, whereas the number of remote assessments increased by 129%. The proportion of patients with drug non-compliance slightly increased during the pandemic, the difference reaching statistical significance in axSpA (19.9% vs 13.2% before the pandemic, p=0.003). The proportion of patients with disease flares remained stable (<15%). There was no increase in mean values of the Bath Ankylosing Disease Activity Index, the Rheumatoid Arthritis Disease Activity Index-5 and the Patient Global Assessment in patients with axSpA, RA and PsA, respectively. CONCLUSION: A short interruption of in-person patient-rheumatologist interactions had no major detrimental impact on the disease course of axSpA, RA and PsA as assessed by patient-reported outcomes.

Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: a survey among EULAR countries.

OBJECTIVES: To investigate how the first wave of COVID-19 pandemic influenced decisions of rheumatologists and health professionals in rheumatology regarding the management of patients with inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: An English-language questionnaire was developed by a EULAR working group and distributed via national rheumatology societies of EULAR countries, EMEUNET and individual working group members. Responses were collected using an online survey tool. Descriptive statistics were calculated. RESULTS: We analysed 1286 responses from 35/45 EULAR countries. Due to containment measures, 82% of respondents indicated cancellation/postponement of face-to-face visits of new patients (84% of them offering remote consultation) and 91% of follow-up visits (96% with remote consultation). The majority of respondents (58%) perceived that the interval between symptom onset and first rheumatological consultations was longer during containment restrictions than before. Treatment decisions were frequently postponed (34%), and the majority (74%) of respondents stated that it was less likely to start a biological disease modifying anti-rheumatic drug (DMARD)/targeted synthetic DMARD during the pandemic, mainly because of patients' fear, limited availability of screening procedures and decreased availability of rheumatological services. Use of (hydroxy)chloroquine (HCQ) and tocilizumab (TCZ) for the COVID-19 indication was reported by 47% and 42% of respondents, respectively, leading to a shortage of these drugs for RMDs indications according to 49% and 14% of respondents, respectively. CONCLUSION: Measures related to containment of COVID-19 pandemic led to a perceived delay between symptom onset and a first rheumatological visit, postponement of treatment decisions, and shortage of HCQ and TCZ, thereby negatively impacting early treatment and treat-to-target strategies.