Efficacy and safety of a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) in the pre-exposure prevention of novel coronavirus infection in immunocompromised pediatric patients with rheumatic diseases. Preliminary results of the first prospective observational cohort study in the Russian Federation
Authors:   National Medical Research Center for Children Health, Moscow, Russian Federation, Kokina M.Yu. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Fomina D.S. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   City Clinical Hospital No 52, Moscow, Russian Federation, Lebedkina M.S. ,   City Clinical Hospital No 52, Moscow, Russian Federation, Mutovina Z.Yu. ,   City Clinical Hospital No 52, Moscow, Russian Federation,   National Association of Non-Governmental Medical Organizations, Moscow, Russian Federation, Zholobova E.S. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Morozov Children City Clinical Hospital, Moscow, Russian Federation, Kurbanova S.Kh. ,   Morozov Children City Clinical Hospital, Moscow, Russian Federation, Nargizyan A.K. ,   Morozov Children City Clinical Hospital, Moscow, Russian Federation, Fetisova A.N. ,   National Medical Research Center for Children Health, Moscow, Russian Federation, Angel A.E. ,   Morozov Children City Clinical Hospital, Moscow, Russian Federation, Dvoryakovskaya T.M. ,   National Medical Research Center for Children Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation, Shilkrot I.Yu. ,   National Association of Non-Governmental Medical Organizations, Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation, Alexeeva E.I. ,   National Medical Research Center for Children Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Central State Medical Academy, Moscow, Russian Federation
Published: July 2023

Rationale. Children with rheumatic diseases receiving immunosuppressants and/or genetically engineered biopharmaceutical drugs (GEBDs) and/or glucocorticosteroids (GCs) are at high risk of developing severe and/or long-term symptoms of novel coronavirus infection. The possibilities of pre-exposure prophylaxis of COVID-19 in this patient population are significantly limited due to the risks of insufficient immunogenicity of the vaccine in the presence of secondary immunodeficiency developed under the conditions of immunosuppressive therapy and exacerbations/increasing activity of the underlying disease after vaccination. The use of a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) may become a priority method for the pre-exposure prevention of COVID-19 in children with rheumatic diseases. Objective. To evaluate the efficacy and safety of using a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) in the pre-exposure prophylaxis of novel coronavirus infection in immunocompromised pediatric patients with rheumatic diseases. Patients and methods. This study enrolled 234 patients aged 12 to 17 years and 11 months with body weight ≥40 kg and a confirmed diagnosis of rheumatic disease. Indications for the use of tixagevimab/cilgavimab for the pre-exposure prophylaxis of COVID-19, as stated in the medication information leaflet, included individuals not infected with SARS-CoV-2 and who had no contact with a person infected with SARS-CoV-2. An additional inclusion criterion was a moderate or severe decrease in immunity due to a pathological condition and/or the use of immunosuppressive medications in patients observed at the National Medical Research Center for Children’s Health and the Morozov Children’s City Clinical Hospital. The tixagevimab/cilgavimab medication was administered intramuscularly as two consecutive injections of each component at a dose of 300 mg (150 mg of each component) to 153 patients, 600 mg (300 mg of each component) to 81 patients. Endpoints used in this study were: • considering efficacy: the incidence rate of novel coronavirus infection in 3 and 6 months after pre-exposure prophylaxis with tixagevimab/cilgavimab in children with rheumatic diseases; • considering safety: exacerbation rates of the underlying disease after pre-exposure prophylaxis with tixagevimab/cilgavimab; the nature, frequency, severity, and outcomes of adverse events, including serious ones directly related to the drug administration. Results. This prospective observational cohort study involved 234 patients with rheumatic diseases, among them were 140 (60%) girls and 94 (40%) boys aged 12 to 17 years and 11 months (median (IQR): 14.79 (13.00, 16.17) years); 168 patients (71.79%) with various types of juvenile arthritis, 66 (28.21%) with systemic connective tissue disorders (SLE, dermatomyositis, systemic sclerosis, vasculitis), 171 (73.08%) with the underlying disease in remission and 63 (26.92%) with exacerbations. All patients received disease-modifying antirheumatic drugs (DMARDs) (methotrexate/mycophenolate, mofetil/cyclophosphamide/sulfasalazine) and/or biological DMARDs (inhibitors of TNF-α/CD20+B-lymphocytes/IL-1, IL-6/IL-17 receptor/T-cell co-stimulation), or targeted synthetic DMARDs (tofacitinib/upadacitinib); 71 (30.34%) patients received oral GCs; 160 (68.37%) patients received 2 to 4 antirheumatic drugs. Before inclusion in the study, 140 (59.83%) children had COVID-19. Within 3 months of preexposure prophylaxis, 2 cases of COVID-19 were reported (0.85%). No exacerbations/increasing activity of the rheumatic disease were recorded in patients immunized in the remission/exacerbation stage with tixagevimab/cilgavimab at doses of 300 mg and 600 mg, respectively. No adverse events directly related to the drug administration were observed. Conclusion. Preliminary results of a prospective observational cohort study indicate a high efficacy and a favorable safety profile of a combination of two monoclonal antibodies against SARS-CoV-2 (tixagevimab/cilgavimab) in the pre-exposure prevention of novel coronavirus infection in immunocompromised pediatric patients with rheumatic diseases. Key words: COVID-19, SARS-CoV-2, monoclonal antibodies, pre-exposure prophylaxis, tixagevimab, cilgavimab, rheumatic diseases, children