Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of bone turnover markers.

BACKGROUND: Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of this study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis. MATERIALS AND METHODS: Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA). RESULTS: Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta-Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agents than only with disease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration. CONCLUSIONS: The authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs further assessment. Age- and sex-adjusted reference rates of bone turnover markers need to be developed for Central European patients in order to assess individual values properly.