Safety Of Eculizumab In Patients Research Articles

Real-life study to assess effectiveness and safety of eculizumab in patients with neuromyelitis optica spectrum disorders in France: protocol for ECUP4, an observational study.

Eculizumab, a humanized monoclonal antibody targeting the C5 complement protein, has been approved for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). The aim of this study is to evaluate the long-term effectiveness and safety of eculizumab in French adults with NMOSD and to describe patients' characteristics, disability, and quality of life using data collected in a real-world setting. This is the protocol for ECUP4, an ongoing prospective, observational, non-comparative, multicenter study conducted in 32 reference centers in France. Eligible patients must also be enrolled in NOMADMUS, a nested cohort of the French national multiple sclerosis registry (OFSEP). The primary endpoint is the annualized relapse rate. Secondary endpoints include the long-term safety of eculizumab, as well as patients' characteristics, treatment outcomes, disability, pain, visual acuity, and quality of life. Visits and treatments follow routine clinical practice. The case report forms (CRF) comprise data recorded in the context of the NOMADMUS cohort, collected during routine visits. The inclusion period is planned for 3 years, with no limitation on the number of patients enrolled. The maximum follow-up duration will be 5.5 years. The efficacy and safety of eculizumab in patients with AQP4+ NMOSD have been demonstrated in randomized clinical trials that showed a significant reduction in the risk of relapse, with a safety profile consistent with other indications. This study will provide clinical and patient-reported evidence of the benefits of eculizumab, using data from a real-world setting in France. This study is registered at the French public repertory Health data Hub, N° F20211228123801. All information can be accessed at: https://www.health-data-hub.fr/.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled. At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Efficacy and safety of eculizumab in patients with treatment-refractory anti-acetylcholine receptor antibody-positive generalised myasthenia gravis previously treated with rituximab

The phase 3 REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) evaluated eculizumab’s efficacy and safety in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (gMG). Although not approved for MG, rituximab has been used in such patients. The aim of this secondary analysis was to assess response to eculizumab in individuals with gMG previously treated with rituximab. Eculizumab is not reimbursed for neurology indications in Italy as of April 2021.

Efficacy and Safety of Eculizumab for Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis.

Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH. PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for prospective interventional studies treating PNH with eculizumab. The primary outcome was the change in lactate dehydrogenase (LDH) levels, whereas secondary outcomes included the change in hemoglobin (Hb) levels, transfusion rates, and adverse drug events. Patients (n=235) from 6 studies were included in this meta-analysis. LDH and Hb levels and transfusion rates decreased significantly at 12, 26 weeks, 12, 15, and >15 months. The most frequent adverse events included nasopharyngitis (effect size [ES]: 0.53; 95% confidence intervals [CI]: 0.47 to 0.60; P=0.00), headache (ES: 0.47; 95% CI: 0.25 to 0.69; P=0.00), upper respiratory tract infection (ES: 0.37; 95% CI: 0.27 to 0.46; P=0.00), nausea (ES: 0.31; 95% CI: 0.24 to 0.38; P=0.00), fatigue, diarrhea, cough, pyrexia, abdominal pain, pain in extremities, and contusion. Eculizumab is an effective and well-tolerated treatment for patients with PNH. It is effective at decreasing LDH levels and transfusion rates while increasing Hb levels. Further studies are needed to explore the safety of eculizumab.

Efficacy and Safety of Eculizumab in Patients with Neuromyelitis Optica Spectrum Disorder Previously Treated with Rituximab: Findings from the Phase 3 PREVENT Study (1788)

Efficacy and Safety of Eculizumab in Patients with Neuromyelitis Optica Spectrum Disorder Previously Treated with Rituximab: Findings from the Phase 3 PREVENT Study (1788)

Variability in management and outcomes of therapy with eculizumab in atypical hemolytic uremic syndrome

ABSTRACTObjectives: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by complement dysregulation. The aim of this study was to establish the efficacy and safety of eculizumab in patients with aHUS in clinical practice and to describe different individualization strategies.Methods: Authors performed an observational, longitudinal, and ambispective study at a tertiary care center. Clinical histories of patients in treatment with eculizumab were reviewed. Effectiveness and safety were assessed with the evolution of analytical parameters, symptoms and concomitant therapies required.Results: Authors included five patients (two children). The patients were followed up from diagnosis and first administration of eculizumab. Four patients discontinued eculizumab: one because he had anti-factor H autoantibodies that could be managed with immunosuppressive therapy, another because of non-response, and the other two because of clinical stabilization, resolution of TMA, and no findings of high-risk mutations in complement factors. Therapy was tapered in the remaining patients in aHUS remission. No adverse events were identified during or after treatment.Conclusion: Eculizumab is an effective and safe treatment for patients diagnosed with primary or secondary aHUS. Personalized treatment, tapering or discontinuation should be taken on an individual basis by a multidisciplinary team in order to increase the cost-effectiveness of this therapy.

A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barré Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS).

BackgroundGuillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation.ObjectiveThis clinical trial aims to evaluate the efficacy and safety of eculizumab, a humanized monoclonal antibody directed against complement component 5, for treatment of GBS.MethodsThe Japanese Eculizumab Trial for GBS (JET-GBS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 33 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3-5) were randomized at a 2:1 ratio to receive either intravenous eculizumab (900 mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow-up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial.ResultsEnrollment for the trial began in August 2015. This trial is still ongoing. All participants have been enrolled, and follow-up will be completed in October 2016.ConclusionsThis study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients.ClinicalTrialUMIN Clinical Trials Registry UMIN 000018171; https:/upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function= brows&action=brows&type=summary&language=J&recptno=R000020978 (Archived by WebCite at http://www.webcitation.org/ 6lTiG8ltG). Clinical Trials.gov NCT02493725; https://clinicaltrials.gov/ct2/show/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL)

Sustained efficacy and safety of eculizumab in patients with atypical hemolytic uremic syndrome with long disease duration and chronic kidney disease: 3-year update

• At the 3-year update: – The median treatment duration was 156 weeks, with a range of 26 to 176 weeks. – Sixteen patients completed ≥30 months of treatment. – Ten patients remained enrolled in the trial at data cutoff. • Patients exited the study following marketing authorization of eculizumab and as commercial supply became available in the study countries. • All patients will be enrolled in an observational 5-year long-term follow-up study (US National Institutes of Health ClinicalTrials.gov Identifier: NCT01522170).