Increased risk for severe COVID-19 in patients with inflammatory rheumatic diseases treated with rituximab.
TL;DR: Accumulating data suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome and that some caution may have to be applied when employing rituximab (RTX), a B-cell depleting b DMARD, in patients with immune-mediated disease.
Abstract: It is currently unknown whether immunosuppressive and/or immunomodulating agents such as biological disease-modifying antirheumatic drugs (bDMARDs) affect the rate and the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections of patients with inflammatory rheumatic diseases (IRDs) While several national authorities have defined patients under immunosuppressive therapy as at risk for severe COVID-19,1 accumulating data from individual cases and also from case series, such as a series from Italy published in the Annals of the Rheumatic Diseases by Monti et al 2 and a report about patients with immune-mediated inflammatory diseases from New York,3 suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome Although the idea of a potentially protective effect of bDMRADs in COVID-19 is intriguing, we feel that extrapolation of these initial data is dangerous and potentially harmful In particular, some caution may have to be applied when employing rituximab (RTX), a B-cell depleting bDMARD, in patients with immune-mediated disease This notion may be illustrated by the following observations:
We recently lost two patients with rheumatoid arthritis (RA) treated with RTX to lethal COVID-19 The first patient, a 71-year-old man with rheumatoid factor positive, …
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TL;DR: In this paper, the efficacy and safety of anti-SARS-CoV-2 mRNA vaccines in a cohort of immunosuppressed patients as compared with healthy controls were presented for the first time.
Abstract: Introduction In light of the SARS-CoV-2 pandemic, protecting vulnerable groups has become a high priority. Persons at risk of severe disease, for example, those receiving immunosuppressive therapies for chronic inflammatory cdiseases (CIDs), are prioritised for vaccination. However, data concerning generation of protective antibody titres in immunosuppressed patients are scarce. Additionally, mRNA vaccines represent a new vaccine technology leading to increased insecurity especially in patients with CID. Objective Here we present for the first time, data on the efficacy and safety of anti-SARS-CoV-2 mRNA vaccines in a cohort of immunosuppressed patients as compared with healthy controls. Methods 42 healthy controls and 26 patients with CID were included in this study (mean age 37.5 vs 50.5 years). Immunisations were performed according to national guidelines with mRNA vaccines. Antibody titres were assessed by ELISA before initial vaccination and 7 days after secondary vaccination. Disease activity and side effects were assessed prior to and 7 days after both vaccinations. Results Anti-SARS-CoV-2 antibodies as well as neutralising activity could be detected in all study participants. IgG titres were significantly lower in patients as compared with controls (2053 binding antibody units (BAU)/mL ±1218 vs 2685±1102). Side effects were comparable in both groups. No severe adverse effects were observed, and no patients experienced a disease flare. Conclusion We show that SARS-CoV-2 mRNA vaccines lead to development of antibodies in immunosuppressed patients without considerable side effects or induction of disease flares. Despite the small size of this cohort, we were able to demonstrate the efficiency and safety of mRNA vaccines in our cohort.
256 citations
25 Mar 2021
TL;DR: In this article, the authors investigated whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.
Abstract: Summary Background Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases Methods In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19 The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group) Severe disease was defined as that requiring admission to an intensive care unit or leading to death Secondary objectives were to analyse deaths and duration of hospital stay The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]) Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD This study is registered with ClinicalTrialsgov, NCT04353609 Findings Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66–6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46–0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55–3·19, p=0·53) Interpretation Rituximab therapy is associated with more severe COVID-19 Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases Funding None
188 citations
TL;DR: In this article, SARS-CoV-2-specific T-cell responses were quantified by IFNγ enzyme-linked immunosorbent spot assays using the Elecsys Anti-SARS CoV2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests.
Abstract: Objectives Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. Methods Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. Results All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p Conclusions The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.
179 citations
TL;DR: In this paper, the authors have assessed antibody response and T cell mediated immune response to the BNT162b2 (Pfizer/BioNTech) vaccine in patients undergoing rituximab (RTX) treatment at the end of the treatment interval.
Abstract: Treatment with rituximab (RTX), a monoclonal antibody targeting CD20, constitutes an important therapeutic strategy for patients with inflammatory rheumatic diseases. Some recent reports have already highlighted the risk of SARS-CoV-2 infection in patients treated with RTX.1–4 Besides the risk of a more severe disease course during B cell depleting therapy, a major concern relates to a risk of reduced immunogenicity of vaccination. Therefore, the question arises if patients should withhold or interrupt RTX therapy around COVID-19 vaccination or delay vaccination. To address this question, we have assessed antibody response and T cell mediated immune response to the BNT162b2 (Pfizer/BioNTech) vaccine in patients undergoing RTX treatment at the end of the treatment interval.
Five patients under regular and recent RTX treatment were selected for COVID-19 vaccination with BNT162b2 (Pfizer/BioNTech). A detailed description of the methods and the patient characteristics (online supplemental table S1) can be found in the online supplemental material. The last RTX infusion was administered between 4 and 12 months ago (online supplemental figure S1). At the time of the vaccination, peripheral CD19+ B cells could only be detected in two patients (online supplemental table S2). Antibodies against the SARS-CoV-2 nucleocapsid …
107 citations
TL;DR: In this paper, the authors select plasma from a cohort of convalescent patients with COVID-19 and selectively deplete immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma.
86 citations
References
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TL;DR: The survey investigated the patients’ health conditions, the presence of contacts with subjects known to be affected by COVID-19 and management of patients with chronic arthritis treated with biological disease-modifying antirheumatic drugs followed up at the biological outpatient clinic in Pavia, Lombardy.
Abstract: Different viral agents are associated with an increased risk of more severe disease course and respiratory complications in immunocompromised patients.1–3 The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) responsible for a severe acute respiratory syndrome (SARS) represents a source of concern for the management of patients with inflammatory rheumatic diseases. Lombardy is the region in Northern Italy with the highest incidence of COVID-19 cases, with more than 33 000 confirmed patients and 1250 requiring admission to the intensive care unit within 1 month. Since the first reports of COVID-19 cases in Italy, we have circulated a survey with a 2-week follow-up contact to patients with chronic arthritis treated with biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) followed up at our biological outpatient clinic in Pavia, Lombardy. The survey investigated the patients’ health conditions, the presence of contacts with subjects known to be affected by COVID-19 and management of …
404 citations
TL;DR: Patients in New York City with known immune-mediated inflammatory disease in whom Covid-19 developed while they were receiving treatment with the drug are described.
Abstract: Covid-19 in Immune-Mediated Inflammatory Diseases The authors describe patients in New York City with known immune-mediated inflammatory disease in whom Covid-19 developed while they were receiving...
372 citations
TL;DR: In this paper, COVID-19 had a mild clinical course in patients with Agammaglobulinemia lacking B lymphocytes, whereas it developed aggressively in Common Variable Immune Deficiency.
Abstract: Summary COVID-19 had a mild clinical course in patients with Agammaglobulinemia lacking B lymphocytes, whereas it developed aggressively in Common Variable Immune Deficiency. Our data offer mechanisms for possible therapeutic targets.
269 citations
TL;DR: The authors rightly recommend a continuous surveillance of patients under immunosuppressants, especially since data are lacking in many systemic autoimmune/inflammatory diseases.
Abstract: In the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (covid-19),1 2 the preliminary experience reported by Monti S and colleagues3 suggests that patients with chronic arthritis (rheumatoid arthritis and spondyloarthritis) receiving bDMARDs (biologic disease-modifying anti-rheumatic drugs) or tsDMARDs (targeted synthetic DMARDs) may not exhibit an increased risk of severe covid-19. These data must be strengthened and confirmed at a larger scale, but remain positive in this drastic context. The authors rightly recommend a continuous surveillance of patients under immunosuppressants, especially since data are lacking in many systemic autoimmune/inflammatory diseases. Notably, anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of vasculitides that can involve the respiratory tract (upper and lower airways) and the recent outbreak of covid-19 raises many specific questions concerning the severity of viral infection in AAV patients as well as the therapy with rituximab. Indeed, rituximab, a monoclonal antibody targeting CD20, has become the cornerstone of treatment in the last decade, but is responsible for long-lasting B-cell depletion and potentially severe infectious events (IE) independently from covid-19.4 A recent observation from our centre illustrates some specific issues with this drug.
A 52-year-old woman was followed for granulomatosis …
117 citations
TL;DR: Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumsumab 2.5mg only achieved two co-primary end points, but there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA -OA.
Abstract: Objective Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up. Methods This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient’s Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study. Results From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE –0.62±0.18, p=0.0006), WOMAC Physical Function (–0.71±0.17, p Conclusion Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups. Trial registration number NCT02709486.
106 citations