eculizumab (Ablyze)

Comparative Evaluation of Rituximab Versus Approved Therapies in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Network Meta-analysis.

Barzegar Mahdi M, Samadzadeh Sara S, Audoin Bertrand B, Berthele Achim A et al.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuro-autoimmune disease. Monoclonal antibodies targeting B cell antigens CD19 and CD20, the interleukin-6 receptor, or the complement cascade are used as preventive therapies to reduce relapse rates. We conducted a network meta-analysis (NMA) to compare the effect of rituximab on time to first relapse with ravulizumab, eculizumab, inebilizumab, and satralizumab in patients with NMOSD who are aquaporin-4 (AQP4)-IgG-positive. A systematic search was conducted in PubMed, Scopus, CINAHL, EMBASE, Web of Science, the Cochrane Library, and gray literature sources up to October 31, 2024, and updated on November 1, 2025, following PRISMA guidelines. A network meta-analysis of randomized and open-label trials was conducted to compare time to first relapse between rituximab and other monoclonal antibody therapies. From 6337 records, 3825 duplicates were removed; 2512 were screened, 2327 excluded, leaving eight trials. The prior treatment, relapse history, and definitions and adjudication of relapse varied across studies. Rituximab showed higher hazard ratio (HR) point estimates for time to first relapse compared with ravulizumab with or without immunosuppressive therapies (IST) (HR 5.00, 95% CI 0.25, 101.01) and eculizumab ± IST (HR 1.17, 95% CI 0.12, 10.89), but were lower compared with satralizumab ± IST (HR 0.29, 95% CI 0.04, 2.23). In patients not receiving IST, rituximab showed numerically higher HR compared with ravulizumab (HR 3.33, 95% CI 0.13, 83.16) and eculizumab (HR 1.59, 95% CI 0.05, 50.17), but lower point estimates compared with inebilizumab (HR 0.31, 95% CI 0.04, 2.31) and satralizumab (HR 0.27, 95% CI 0.03, 2.21). This NMA showed hazard ratio point estimates favoring eculizumab and ravulizumab over rituximab. However, wide, overlapping confidence intervals and between-study heterogeneity indicate substantial uncertainty. Head-to-head trials or registry-based studies are needed to determine the most effective treatment for AQP4-IgG-positive NMOSD.

A decade of complement inhibition in post-transplant atypical HUS: outcomes with eculizumab and ravulizumab.

Gopireddy Naga Sumanth Reddy NSR, Kumar Abhishek A, Smith Richard J H RJH, Nester Carla M CM et al.

Drug Induced Thrombotic Microangiopathy in Cancer Patients: A Clinicopathologic Series.

Pak Wai Lun Will WLW, Al Haddad Nadia N, Knezevic Andrea A, Salvatore Steven S et al.

Drug-induced thrombotic microangiopathy (TMA) is a major sequela of cancer therapies. The diagnosis of drug-induced TMA is often presumptive, making accurate clinical characterization difficult. We retrospectively reviewed clinical presentation and outcomes of 53 patients with biopsy-proven renal TMA due to cancer therapies in a cancer center between 2001 and 2023. Median age at presentation was 64 (44-81) years and our cohort was 72% (38/53) female. Most common malignancies treated were pancreatic (19%), breast (17%), ovarian (15%) and lung cancer (15%). Forty-one patients (77%) presented with acute kidney injury (AKI), out of which nine patients (17%) required dialysis. Most common implicated drugs were gemcitabine (51%), bevacizumab (25%), doxorubicin (15%), and various tyrosine kinase inhibitors (19%) including epidermal growth factor receptor blocker erlotinib (4%). Cessation of the offending drug was the mainstay of management in 51 patients (96%); other treatment strategies included steroid (15%) and eculizumab (8%). After median follow-up of 4 (1.1-7.1) years, median overall survival was 2.1 years and median kidney failure-free survival was 1.8 years. Among patients with AKI, 16 patients (39%) had kidney recovery within a year. One out of nine patients requiring dialysis was weaned off within a year. Older age, lower glomerular filtration rate at presentation and thrombocytopenia were associated with worse kidney prognosis. Chronic TMA was noted upon kidney biopsy in most patients (85%). Pathologic findings associated with worse kidney outcome were the presence of microvascular thrombi and endothelial swelling. Though limited by its retrospective nature, our study suggests that doxorubicin and erlotinib are underrecognized causes of drug-induced TMA. Many patients' biopsies had chronic changes in glomeruli, arterioles, as well as small arteries, indicating that mild, ongoing endothelial injury is present before development of overt TMA. Clinical vigilance with early cessation of offending drug may help kidney recovery.

Long-Term Ravulizumab Efficacy and Safety in AQP4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: Final CHAMPION-NMOSD Results.

Pittock Sean J SJ, Barnett Michael H MH, Bennett Jeffrey L JL, Berthele Achim A et al.

Ravulizumab, a complement component 5 inhibitor, was approved for the treatment of adults with anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) based on results of the primary treatment period (PTP) of CHAMPION-NMOSD, a phase 3, open-label, external placebo-controlled trial. Here, we report the final efficacy and safety results of CHAMPION-NMOSD (PTP and the long-term extension [LTE]). Adult patients with AQP4-Ab+ NMOSD received an IV, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. After completion of the PTP (up to 2.5 years), patients could enter the LTE. The primary endpoint was time to first adjudicated on-trial relapse. The placebo group of the eculizumab phase 3 trial PREVENT was used as an external comparator because eculizumab availability at CHAMPION-NMOSD initiation precluded the use of concurrent placebo control. Of 58 patients enrolled in the trial, 56 entered and 55 completed the LTE. The overall median (range) follow-up was 170.3 (11.0-243.0) weeks, with 100.8 (53-137) weeks during the LTE. No patient receiving ravulizumab had an adjudicated on-trial relapse throughout the PTP (84.0 patient-years) and LTE (105.7 patient-years); relative reduction in risk of relapse vs placebo (n = 47) was 98.9% (95% CI 91.8-100; p < 0.0001). Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 94.8% and 27.6% of patients, respectively, during the PTP and LTE. Most TEAEs were grade 1 and unrelated to ravulizumab. One patient discontinued ravulizumab because of TEAEs. Two cases of meningococcal infection occurred during the PTP; none occurred in the LTE. One death due to hypertensive heart disease (unrelated to ravulizumab) occurred during the LTE. Long-term ravulizumab treatment (median follow-up, >3 years) continued to show significant relapse risk reduction in patients with AQP4-Ab+ NMOSD, and the safety profile was consistent with the known safety profile for ravulizumab. ClinicalTrials.gov, NCT04201262; EudraCT: 2019-003352-37. Submitted December 11, 2019. First patient enrolled: December 13, 2019. clinicaltrials.gov/study/NCT04201262. This study provides Class III evidence that long-term ravulizumab treatment, as compared with placebo, decreases the probability of clinical relapse in patients with AQP4-Ab+ NMOSD.