ABSTRACT
BackgroundCOVID-19 is associated with higher morbidity and mortality burdens in immunocompromised individuals, including patients with systemic lupus erythematosus (SLE;1). These patients might benefit from treatment with anti-SARS-CoV-2-specific antiviral agents and monoclonal antibodies, but clinical evidence is to date limited.Objectivesto comparatively assess the course of COVID-19 in patients with SLE treated or untreated with COVID-19-specific agents.MethodsPatients with SLE and COVID-19 treated with antivirals and/or monoclonal antibodies from February 2020 to December 2022 were identified within a three-centre cohort of tertiary referral centres and age-, sex- SLE extension- and SLE duration-matched 1:2 with patients with a history of untreated COVID-19. Data on COVID-19 presentation, course (including time to viral clearance) and sequelae, along with SLE treatment at COVID-19 onset and SLE course after COVID-19 were collected. COVID-19 severity at presentation was quantitated through a 0-4 analogue scale [2]. Data are expressed as median (interquartile range, IQR) unless otherwise specified.ResultsOver three years, 39% of patients with SLE had at least one COVID-19 event. Eighteen subjects (16 women) were treated with antivirals (n=12) or monoclonal antibodies (n=6) and were matched with 36 controls. There was no difference in the frequency of organ involvement between the two groups. Treated patients were receiving significantly higher prednisone daily doses at COVID-19 onset (6.25 (0-10) vs 0 (0-2.5) mg;p=0.005) and had a higher prevalence of previous high-dose steroid treatments (83% vs 47%;p=0.019) compared to controls. SLE disease activity index (3 (0-5) vs 1 (0-4)) and SLE International Collaborating Clinics Damage Index scores (1 (0-3) vs 0 (0-1)) were also numerically higher in treated patients at COVID-19 onset. Patients in the treated group had more severe COVID-19 at presentation but showed no significant differences with control subjects in terms of COVID-19 resolution, prevalence of sequelae and viral clearance (Table 1). There was also no difference in flare occurrence between the two groups (Log-rank=0.02, p=0.889). Two patients reported mild adverse events with monoclonal antibodies (muscle cramps and chest pain, both self-resolving).ConclusionThese data support the safe use of COVID-19 specific treatments in patients with SLE. Patients treated with antivirals and monoclonal antibodies had a favourable COVID-19 course, despite a more severe presentation and a higher risk of deterioration due to SLE and corticosteroid treatment burden, suggesting the potential efficacy of COVID-specific treatments in preventing severe COVID-19 in patients with SLE.References[1]Strangfeld A et al, Ann Rheum Dis, 2021[2]World Health Organization. Clinical management of COVID-19;Interim guidance 27 May 2020.Table 1.COVID-19 presentation and courseTreated (n=18)Untreated (n=36)Number of vaccine doses3 (2-3)3 (2-3)Time from last vaccine administration (days)118 (53-184)134 (30-210)COVID-19 featuresWHO class at presentation1 (1-1)**0 (0-1)Symptoms at presentation: n(%)Dyspnoea3 (17)3 (8)Fever10 (56)22 (61)Upper Respiratory Symptoms16 (89)29 (81)GI symptoms1 (6)2 (6)Pneumonia3 (17)3 (8)COVID-19 courseTime to symptom resolution (days)5 (4-8)7 (3-8)Time to viral clearance (days)10 (7-14)9 (7-14)Any complication: n(%)1 (6)6 (17)Hospitalisations: n(%)1 (6)0 (0)Long COVID: n(%)3 (17)6 (17)Deaths: n(%)0 (0)1 (3)AcknowledgementsWe thank Dr. Giordano Vitali and his staff for assisting and treating patients with SLE and COVID-19 from IRCCS San Raffaele Hospital in the local mild COVID-19 clinic.Disclosure of InterestsGiuseppe Alvise Ramirez Consultant of: Astrazeneca, Maria Gerosa: None declared, Daniel Arroyo-Sánchez: None declared, Chiara Asperti: None declared, Lorenza Maria Argolini: None declared, Gabriele Gallina: None declared, Chiara Bellocchi: None declared, Martina Cornalba: None declared, Isabella Scotti: None declared, Ilaria Suardi: None declared, Lorenzo Beretta: None declared, Luca Moroni Consultant of: strazeneca, Enrica Bozzolo: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB, Lorenzo Dagna Consultant of: Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), and Takeda, Grant/research support from: Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.
ABSTRACT
Introduction Les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD) n’ont pas été inclus dans les études de tolérance des vaccins contre le SARS-CoV-2 et sont souvent inquiets quant à la tolérance de la vaccination. Notre objectif est d’étudier la tolérance des vaccins contre le SARS-CoV-2 chez les patients atteints de maladies musculosquelettiques inflammatoires/auto-immunes (I-RMD). Patients et méthodes Pour cela, nous avons créé avec l’EULAR un registre international de cas rapportés par les médecins rhumatologues et internistes de patients atteints d’I-RMD et de RMD non inflammatoire (NI-RMD) vaccinés contre le SARS-CoV-2. Du 5 février 2021 au 27 juillet 2021, nous avons recueilli des données sur la démographie, la vaccination, le diagnostic de RMD, l’activité de la maladie, les traitements immunomodulateurs/immunosuppresseurs, les poussées, les événements indésirables (EI) et les infections COVID-19 chez les patients vaccinés. Les données ont été analysées de manière descriptive. Résultats L’étude a inclus 5121 participants de 30 pays, la majorité de France (40 %), Italie (16 %) et Portugal (14 %), 90 % avec des I-RMD (n=4604, 68 % de femmes, âge moyen 60,5 ans) et 10 % avec des NI-RMD (n=517), 77 % de femmes, âge moyen 71,4 ans. La polyarthrite rhumatoïde (33 %), les connectivites (18 %), les spondyloarthrites (11 %), le rhumatisme psoriaqique (10 %) et les vascularites (12 %) étaient les diagnostics les plus fréquents ;54 % des patients ont reçu des traitements de fond synthétiques conventionnels (csDMARD), 42 % des DMARD biologiques ou ciblés et 35 % des immunosuppresseurs. La plupart des patients ont reçu le vaccin Pfizer/BioNTech (70 %), 17 % AstraZeneca/Oxford et 8 % Moderna. Une infection COVID post-vaccination a été signalée dans 0,7 à 1,1 % des cas, selon le statut vaccinal (entièrement/partiellement vacciné) et le groupe RMD. Des poussées d’I-RMD ont été signalées dans 4,4 % des cas (0,6 % de poussées sévères), dont 1,5 % ont entraîné des changements de médicaments. Des EI ont été signalés dans 37 % des cas (37 % I-RMD, 40 % NI-RMD), des EI sévères dans 0,4 % des cas, très divers et avec une fréquence comparable et même inférieure à celle observée chez les patients atteints de NI-RMD (1,1 %). Discussion La tolérance au vaccin n’était pas différente entre les groupes I-RMD et NI-RMD. Dans les essais cliniques de vaccins à ARN contre le SRAS-CoV-2 dans la population générale, les taux d’EI graves étaient très semblables à ceux de notre étude, allant de 0,4 % à 0,6 % dans le groupe vacciné et de 0,5 % à 0,6 % dans le groupe témoin, ce qui suggère que ces EI graves ne sont pas nécessairement liés au vaccin. Conclusion Il s’agit de la plus grande étude de la tolérance des vaccins anti-SRAS-CoV-2 chez près de 5000 patients atteints de maladies inflammatoires/auto-immunes rhumatologiques. Le profil de sécurité des vaccins contre le SRAS-CoV-2 chez les patients atteints d’I-RMD était rassurant, et comparable à celui des patients atteints de NI-RMD. La majorité des patients ont bien toléré leur vaccination, avec de rares poussée d’I-RMD et de très rares EI sévères probablement non liés à la vaccination. Ces résultats devraient rassurer les rhumatologues et les personnes vaccinées, et favoriser la confiance dans la sécurité du vaccin COVID-19 chez les patients atteints de I-RMD.
ABSTRACT
Background: The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system. Objectives: Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines. Methods: The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff;patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented. Results: As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine;mycophenolate;cyclosporine;cyclophosphamide;tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown;66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/ SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae). Conclusion: The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%;1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system.