RESUMEN
The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus;currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur"). Objective - to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study. Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 - rheumatoid arthritis, 9 - Sjogren's syndrome (SS), 4 - IgG4-related disease, 3 - systemic lupus erythematosus (SLE), 3 - dermatomyositis (DM), 2 - systemic scleroderma (SSD). Median age was 59 (19-82) years;male: female ratio - 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age - 45 (35-71) years;male: female ratio - 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions. Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV - 10, SS - 3, SSD - 2, SLE - 1, DM - 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1-2), there were no deaths. Good TC's tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA - 3 MPA - 1, RA - 2, SLE - 1, IgG4-related disease - 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death. Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
RESUMEN
Coronavirus disease 2019 (COVID-19) can manifest with a wide range of extrapulmonary symptoms and have long-term consequences (so-called post-covid syndrome (PCS) or "long COVID-19"). Manifestations of PCS show a wide clinical spectrum and include cardiac, pulmonary, neurological, gastrointestinal, dermatological, mental symptoms, vascular thrombosis and avascular necrosis (AVN) of the bones. We present our own observations of the development of bone's AVN in 3 patients who underwent COVID-19 with bilateral lung disease, in whom after 4-6 months the first signs of AVN were noted and characterized by a progressive multifocal lesion, which was accompanied by an increase of C-reactive protein concentration. The pathogenetic mechanisms of AVN development in the framework of PCS are discussed. The importance of conservative and surgical methods in the treatment of the disease are considered. Since the development of AVN of various localizations with a long latent period is possible after COVID-19, long-term monitoring of patients is required. Further study of the problem of PCS in general and AVN in particular is required. Copyright © 2022 Ima-Press Publishing House. All rights reserved.
RESUMEN
In the last decade, anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (SV) has been treated with the anti-B-cell drug, rituximab (RTM) both for induction and maintenance therapy. One of the problems of the treatment with RTM in patients with ANCA-SV is the risk of late-onset neutropenia (LON), mechanisms of development of which have not been studied enough yet. Objective: To evaluate the incidence and outcomes of LON in patients with ANCA-SV treated with RTM. Patients and methods. A retrospective analysis of the register of 140 patients with ANCA-SV who received RTM treatment at the V.A. Nasonova Research Institute of Rheumatology from 2009 to 2021 years. The median duration of RTM treatment was 49 (6–121) months, the median of the total RTM dose was 3.5 (0.5–9.5) grams. The duration of follow-up exceeded 6 months after the first administration of RTM. Results and discussion. LON was detected in 16 (11.4%) patients, of which 6 suffered from Wegener's granulomatosis with polyangiitis (GPA), 4 – microscopic polyangiitis (MPA), 4 – Churg-Strauss eosinophilic granulomatosis with polyangiitis (EGPA) and 2 – undifferentiated ANCA-SV. In 8 (50%) out of 16 patients, LON developed within 2 months after the 1st course of RTM, in the remaining 8 patients, on average, after 10 (4–15.5) months. A lethal outcome was documented in 5 (31.2%) of 16 cases of LON (1 with MPA, 3 with GPA, and 1 with EGPA) on average 2 (1.5–9) months after the 1st course of RTM, at the same time, in 4 patients LON was complicated by pneumonia, including 2 with septic shock, in another 1 case LON was combined with the development of acute myocardial infarction and progression of chronic renal failure. Overall mortality among 140 patients with ANCA-SV treated with RTM was 11.4%, while in cases with a fatal outcome, the frequency of LON reached 31.2%. Conclusion. Thus, LON induced by RTM is a common (11%) and clinically significant consequence of B-cell depletion in patients with ANCA-SV, in every 5th case it is complicated by serious infections (including sepsis in 13%) and accounts for a significant proportion in the structure of lethal outcomes (31.2%). Patients treated with RTM require careful monitoring of absolute neutrophil count both during the first months after initiation of anti-B-cell therapy and thereafter. In the combined administration of RTM with cytotoxic drugs (primarily cyclophosphamide) in patients with ANCA-SV, it is necessary to consider the risk of LON developing, secondary immunodeficiency, and infectious complications. During the coronavirus pandemic, one should remember that treatment with interleukin 6 inhibitors used in severe COVID-19 can also be accompanied by neutropenia and requires careful dynamic monitoring of the absolute number of neutrophils in patients with ANCA-SV treated with RTM. It is necessary to inform both patients and physicians of the risk of LON development during the treatment of RTM in ANCA-SV and other rheumatic diseases. © Institut français des relations internationales.
RESUMEN
Actual problems of rheumatology include the possibility of developing a wide range of long-term consequences of COVID-19, so-called post-COVID syndrome (PCS). The results of our own research are presented, during which among 45 patients over 18 years with rheumatic diseases (RD) PCS was detected in 20% cases: 6 of them had ANCA-associated vasculitis (AAV) and one each for rheumatoid arthritis, juvenile arthritis and osteoarthritis. In AAV cases PCS was more severe and varied than in other RD: lung lesions according to computed tomography (up to the damage 75% of the lung parenchyma), skin and nervous (Guillain – Barré syndrome) lesions, myalgias, arthralgias were present. In most patients PCS ended in recovery, sudden death occurred only in the patient with AAV. The frequency of RD’s relapses in patients with PCS was 9%. Relapses were not noted in AAV, against the background of anti-B cell therapy with rituximab. Our own results and literature data indicate that patients with RD after COVID-19 need careful continuous monitoring to detect long-term complications of coronavirus infection and early diagnosis of relapses of the underlying disease.