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Background: To our knowledge, no published work has described precisely the severity and evolution of SARS-CoV-2 infection in patients with spondyloarthritis (SpA). Data on COVID-19 from cohorts of patients with immune-mediated infam-matory diseases concern small samples of SpA. Objectives: Our objective was to describe the severity and course of COVID-19 in a large cohort of patients with SpA, including axial SpA (axSpA) and psoriatic arthritis (PsA), and to identify factors associated with severe forms. Methods: Patients: individuals with Spondyloarthritis (SpA) from the French RMD COVID-19 cohort (observational, national, multicenter cohort) with a diagnosis of COVID-19 (clinical, PCR, CT or serology) were included. Data collected: demographics, type of SpA, comorbidities, treatments, severity of COVID-19. Severity of COVID-19 was graded according to care needed: mild = outpatient care;moderate = non-intensive hospital treatment;severe = intensive care unit admission or death;severe = moderate or severe. Statistical analyses: Logistic regression models were used to identify factors associated with these severe forms. All variables with p <0.20 in the univariate analysis were proposed in the multivariate model. Treatment variables (non-ste-roidal anti-infammatory drugs (NSAIDs), methotrexate (MTX), sulfasalazine (SLZ), TNF inhibitors (TNFi), IL-17 inhibitors (IL-17i) and IL-23p19/p40 inhibitors (IL-23p19/p40i)) were included in the models, even if p≥0.20. Results: Between March 2020 and April 2021, 626 SpAs reported COVID-19 with a mild course in 508 cases (81.1%), moderate in 93 cases (14.8%), and severe in 25 cases (3.9%), including 6 deaths. The cohort analyzed included 349 women (55.8%), mean age 49.3 ± 14.1 years, mean BMI 27.1 ± 5.4 with 403 axSpA (64.4%), 187 PsA (29.9%) and 36 other SpA, duration of disease 11.3 ± 9.8 years;352 (56.2%) had at least one comorbidity, of which obesity (23.6%), hypertension (15.5%), and smoking (10.4%) were the most frequent. Among them, 104 were treated with NSAIDs (16.6%), 186 with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) including 156 MTX, and 460 (73.5%) with biological DMARDs (379 TNFi, 57 IL-17i, 15 IL-23p19/p40i, 9 others). The following variables were associated with severe COVID-19 outcomes: age, body mass index, chronic obstructive lung disease, cardiovascular disease, diabetes, hypertension, interstitial lung disease, renal failure, and corticosteroids intake. The factors independently associated with severe COVID-19 outcomes were cor-ticosteroid intake (3.15 [CI95%: 1.46-6.76], p 0.004), and age (OR=1.06 [CI95%: 1.04-1.08], p <0.001] while anti-TNF (OR=0.26 [CI95%: 0.09-0.78], p=0.01]) was protective. NSAIDs intake (OR=0.97 [CI95%: 0.48-1.98]), SLZ (OR=7.9 [CI95%: 0.60-103]), or anti-IL17 (OR=0.37 [CI95%: 0.10-1.31]) was not associated with infection severity. Conclusion: The course of COVID-19 was mild for the majority of SpA patients (81.1%). Corticosteroid intake was associated with more severe COVID-19 outcomes, whereas TNFi were found to be protective.
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Background: Patients with autoimmune/infammatory rheumatic diseases (AIRD) were suspected to be an at-risk population of severe COVID-19. However, whether this higher risk is linked to the disease or to its treatment is difficult to determine. Objectives: To identify, among AIRD patients, factors associated with occurrence of moderate-to-severe COVID19 infection and to evaluate if having an AIRD was associated with an increased risk of severe form of COVID19 infection (defned by hospitalization in ICU or death), compared to general population. Methods: Data source: The 'Entrepôt des Données de Santé (EDS)' collect data from electronic health records of all patients hospitalized or followed in the AP-HP (39 hospitals in Paris area, France). The French RMD COVID19 cohort is a national multi-center cohort that included patients with confrmed AIRD and diagnosed with COVID-19. All AIRD patients diagnosed with COVID-19 before September 2020 from both cohorts were included.-We Identifed factors associated with severe COVID-19 was made in a combined analysis of the 2 cohorts.-Then, we compared COVID-19 infection severity in the EDS-COVID database in AIRD patients and controls, by a propensity score (PS)-matched case-control (1:4) study Results: Among 1213 patients (334 in EDS and 879 in RMD cohort), 195 (16.1%) experienced a severe COVID19. In multivariate analysis, greater age, history of interstitial lung disease, arterial hypertension, obesity, sarcoidosis, vas-culitis, auto-infammatory disease and treatment with corticosteroids or rituximab were associated with severe COVID-19 (Table 1). Among 35741 COVID-19 patients in EDS, 316 with AIRD were compared to 1264 PS-matched controls. Severe form occurred in 118 (37,3%) AIRD cases and 384 (30.4%) controls (Adjusted OR (aOR) for severe form= 1.43 [1.1;1.9], p=0,01). In analysis restricted to rheumatoid arthritis (RA) and spondylarthritis (SpA), no increased risk of severe form (aOR=1.11 [0.68;1.81]) form or death (aOR=1.00 [0.55;1.81]) was observed. Conclusion: In this multicenter study we confirmed that AIRD patients treated with rituximab or corticosteroids were at increased risk of severe COVID-19, as were those with vasculitis, auto-inflammatory disease, and sarcoidosis. Also, when compared to controls from the same cohort of hospitalized patients, AIRD patients had, overall, an increased risk of severe COVID-19, increased risk not observed in an analysis restricted to patients with RA or SpA.
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Introduction Il n’y a pas, à notre connaissance, de publication décrivant précisément la sévérité et l’évolution de l’infection à SARS-CoV-2 dans la spondyloarthrite (SpA). Les données sur la COVID-19 issues des cohortes de patients avec maladies inflammatoires à médiation immunitaire concernent de faibles effectifs de SpA. Notre objectif était de décrire la sévérité et l’évolution de la COVID-19 dans une large cohorte de patients atteints de SpA (SpA axiale et rhumatisme psoriasique) et d’identifier les facteurs associés aux formes sévères. Patients et méthodes Patients : spondyloarthrites (SpA) de la French RMD COVID-19 cohort (cohorte observationnelle, nationale, multicentrique) avec un diagnostic de COVID-19 (clinique, PCR, scanner ou sérologie). Données collectées : démographiques, type de SpA, comorbidités, traitements, gravité de la COVID-19. La gravité de la COVID-19 a été classée en fonction des soins nécessaires : bénin=soins ambulatoires ;modéré=traitement hospitalier non intensif ;sévère=admission en unité de soins intensifs ou décès ;grave=modéré ou sévère. Analyses statistiques : des modèles de régression logistique ont été utilisés pour identifier les facteurs associés à ces formes graves. Toutes les variables avec p<0,20 en analyse univariée ont été proposées dans le modèle multivarié. Les variables de traitement (AINS, méthotrexate [MTX], sulfasalazine [SLZ], anti-TNF et anti-IL17) étaient incluses dans les modèles, même si p≥0,20. Résultats Entre mars 2020 et avril 2021, 626 SpA ont déclaré une COVID-19 dont l’évolution avait été bénigne dans 508 cas (81,1 %), modérée dans 93 cas (14,8 %) et sévère dans 25 cas (3,9 %), dont 6 décès. La cohorte analysée comprenait 349 femmes (55,8 %), âge moyen 49,3±14,1 ans, IMC moyen 27,1±5,4 avec 403 SpA axiale (64,4 %), 187 RPso (29,9 %) et 36 autres SpA, durée de la maladie 11,3±9,8 ans ;352 (56,2 %) avaient au moins une comorbidité dont l’obésité (23,6 %), l’hypertension artérielle (15,5 %) et le tabagisme (10,4 %) étaient les plus fréquentes. Parmi eux, 104 étaient traités par AINS (16,6 %), 186 par csDMARD dont 156 méthotrexate, et 460 (73,5) % par biomédicaments (379 anti-TNF, 57 anti-IL17 : 57, 15 anti-IL12/23, 9 autres). Les facteurs indépendamment associés à une COVID-19 grave étaient la corticothérapie (OR=2,83 [IC95 % : 1,41–5,66]) et l’âge (OR=1,07 [1,05–1,09]) alors le genre féminin (OR=0,64 [0,41–0,99]) et les anti-IL17 (OR=0,51 [0,32–0,81]) avaient un caractère protecteur. Un traitement par AINS (OR=0,91 [IC95 % : 0,47–1,77]), par sulfasalazine (OR=6,81 [0,59–77,41]) ou par anti-TNF (OR=0,67 [0,33–1,35]) n’était pas associé à la gravité de l’infection. Conclusion L’évolution de la COVID-19 a été bénigne pour la majorité des patients atteints de SpA (81,1 %). La corticothérapie était associée à des infections plus graves alors que les anti-IL17 avaient un caractère protecteur.
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Background: Various observations have suggested that the course of the COVID-19 infection may be less favorable in patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving rituximab (RTX). Objectives: To investigate whether treatment with RTX is associated with severe infection and death. Methods: We performed an observational, multicenter, French national cohort study querying the French RMD COVID-19 cohort, including highly suspected/ confirmed iRMD-COVID-19 patients. The primary endpoint was to assess the severity rate of COVID-19. Severe disease was defined by hospitalization in intensive care unit or death. The secondary objectives were to analyze death rate and length of hospital stay. Two control groups were considered for comparison with RTX treated patients: a first group including all non-RTX treated iRMD patients and a second consisting on RTX untreated iRMD patients with diseases for which RTX is a recognized therapeutic option. Adjusting on potential confounding factors was performed by using inverse probability of treatment weighting (IPTW) propensity score method. Results: We collected a total of 1090 records. Patients were mainly females (67.3%, 734/1090) with a mean age of 55.2±16.4 years, and 51.1% (557/1090) were over the age of 55. Almost 70% of the population had at least one comorbidity (756/1090). A total of 63 patients were treated with RTX, mainly for rheumatoid arthritis (RA) (31/63, 49.2%). RTX treated patients were more likely to be males, with older age, higher prevalence of comorbidities and corticosteroid use. The control population consisted on 1027 non-RTX treated iRMD patients, and 495 RTX untreated iRMD patients with diseases for which RTX is a recognized therapeutic option. Of the 1,090 patients, 137 developed severe disease (12.6%). After adjusting on 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), severe disease was confirmed to be observed more frequently in patients receiving RTX compared to all RTX untreated iRMD patients (effect size, ES 3.26, 95% confidence interval, CI 1.66 to 6.40, p<0.001) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (ES 2.62, 95% CI 1.34 to 5.09, p=0.005). Patients who developed a severe disease had a more recent rituximab infusion compared to patients with mild or moderate disease. Indeed, the time between the last infusion of rituximab and the first symptoms of COVID-19 was significantly shorter in patients who developed a severe form of COVID-19 (Figure 1). Eighty-nine patients in our cohort died, resulting in an overall death rate of 8.2%. Death rate was numerically higher in RTX treated patients (13/63, 20.6%) compared to all RTX untreated iRMDs patients (76/1027, 7.4%) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (49/495, 9.9%). After considering the previously described confounding factors, the risk of death was not significantly increased in patients treated with RTX compared to all RTX untreated iRMDs patients (ES 1.32, 95% CI 0.55 to 3.19, p=0.53) (Table 2) and the subgroup of untreated RTX patients with diseases eligible for RTX therapy (ES 1.48, 95% CI 0.68 to 3.20, p=0.32). In line with a more severe COVID-19 disease, the length of hospital stay was markedly longer in patients treated with RTX compared to both untreated RTX patient groups. Conclusion: RTX therapy is associated with a more severe COVID-19 infection. RTX will have to be applied with particular caution in patients with iRMDs.