Zeitschrift fur Rheumatologie最新文献

Rituximab (RTX) causes B‑cell depletion by binding to the CD20 antigen. A less well-known adverse drug reaction of RTX is late-onset neutropenia (LON), which occurs approximately 6 months after treatment initiation. As clinical management, regular differential blood cell counts should be performed during RTX treatment. Besides a watch-and-wait strategy, supportive administration of granulocyte colony-stimulating factor (G-CSF) can be discussed for acute LON episodes. Re-exposure to RTX after LON has occurred is generally considered acceptable after diligent benefit-risk evaluation and thorough patient information. In this case series, we would like to present 2 cases of rheumatology patients with severe LON after RTX administration.

Despite substantial advances in the treatment of inflammatory rheumatic diseases, not all patients respond adequately to conventional, biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD). In particular, in systemic diseases such as systemic sclerosis or systemic lupus erythematosus, disease progression can lead to irreversible organ damage and increased mortality. For these refractory patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) has been successfully used for the past 30 years. The available data suggest that by the elimination of autoreactive immunological memory and the resetting of the immune system drug-free remission is possible; however, this approach can be associated with substantial side effects, including the risk of transplantation-related mortality (TRM), which can substantially vary depending on the disease, treatment protocol and individual risk factors and is between 0% and 5% in currently available studies. The TRM can be minimized by careful patient selection, treatment by a qualified multidisciplinary team and standardized treatment and monitoring protocols. This review article presents the current state of research and the results of an updated recommendation of an international expert panel of the European Society for Blood and Marrow Transplantation (EBMT) regarding the use of HSCT in inflammatory rheumatic diseases. These recommendations include detailed information on the indications, contraindications and warning signals for disease and comprehensive recommendations for diagnostic evaluation and monitoring. They are intended to guide rheumatologists in identifying suitable patients and providing interdisciplinary care.

Background: Chimeric antigen receptor T-cells (CAR T-cells) are an effective therapeutic approach in the treatment of B-cell driven malignancies. In addition to malignant B-cells, autoreactive B-cells are important targets for CD19 CAR T-cells, as they are a source of autoantibody production and support both the onset and progression of systemic lupus erythematosus (SLE). We and others have shown that their use in severe and therapy-refractory cases of SLE is effective and, moreover, safe.

Objective: The current status and an interim analysis of the efficacy and safety of CD19-CAR T‑cell therapy in SLE.

Material and methods: Patients with severe, treatment-refractory, and active SLE received autologous CD19-CAR T‑cell therapy (MB19.1, Miltenyi Biotec, Bergisch Gladbach, Germany) as part of an individual compassionate treatment attempt and are regularly followed up at our center.

Results: 11 patients with progressive, therapy-refractory SLE received an autologous CD19 CAR T-cell therapy as part of an individual treatment attempt. The median follow-up time is 2.5 years [0.5 - 4 years]. All patients achieved a DORIS remission within 6 months. Immunosuppressive therapy was completely discontinued in all patients. Five out of the 11 patients experienced grade 1 cytokine release syndrome (CRS). Grade 2 CRS was observed only once. No higher-grade CRS occurred in this cohort. So far, no neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS) has been observed in our SLE patients. All patients remain in a sustained and drug-free remission to date. One patient experienced an SLE flare. Initial data, despite similar CD19 CAR T-cell expansion and kinetics, suggest a better safety profile of CD19 CAR T-cell therapy in SLE compared to lymphoma cohorts. Additionally, adaptive immunity in SLE patients recovers rapidly after CD19 CAR T-cell therapy.

Conclusion: The use of CD19-CAR T‑cells in patients with severe SLE proved to be safe and effective.

The VEXAS (vacuoles, E1 enzyme, X‑linked, autoinflammatory, somatic) syndrome is an acquired autoinflammatory disease, which is based on somatic mutations in the UBA1 gene and described as an hematoinflammatory disease. It is clinically expressed as an inflammatory systemic disease with general vegetative symptoms and organ manifestations of the skin, lungs and the hematopoietic system. The symptoms are not uncommonly refractory to conventional anti-inflammatory therapeutic agents. The disease is associated with a clearly increased mortality and morbidity.

Objective: The study aimed to assess whether a denosumab biosimilar is as effective and safe as the original denosumab for treating postmenopausal osteoporosis.

Methods: A comprehensive search of MEDLINE, Embase, and the Cochrane databases identified six randomized controlled trials (RCTs) relevant to this study. The meta-analysis focused on evaluating percentage changes in bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip, alongside monitoring adverse events (AEs), serious adverse events (SAEs), and infections.

Results: The analysis encompassed 1784 patients, with 978 and 816 receiving biosimilar and originator therapy, respectively. Regarding standardized mean differences (SMDs) for BMD changes, a lumbar spine SMD of -0.048 (95% confidence interval [CI]: -0.142 to 0.046; P = 0.317), femoral neck SMD of 0.089 (95% CI: -0.068 to 0.247; P = 0.266), and total hip SMD of 0.029 (95% CI: -0.153 to 0.212; P = 0.755) were found, showing no significant differences between the two treatments. Safety profiles were also comparable, with odds ratios (ORs) of 1.168 (95% CI: 0.795-1.716; P = 0.428) for AEs, 1.120 (95% CI: 0.644-1.946; P = 0.689) for SAEs, and 1.576 (95% CI: 0.657-3.780; P = 0.308) for infections.

Conclusion: The denosumab biosimilars demonstrated efficacy and safety profiles comparable to the originator in the treatment of postmenopausal osteoporosis.