scholarly journals Correction to: The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab

2020 ◽  
Author(s):  
Kazuki Tanaka ◽  
Brigitte Adams ◽  
Alvaro Madrid Aris ◽  
Naoya Fujita ◽  
Masayo Ogawa ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Pediatric Patients ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Uremic Syndrome ◽  
Previously Treated ◽  
Long Acting

scholarly journals The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab

2020 ◽  
Author(s):  
Kazuki Tanaka ◽  
Brigitte Adams ◽  
Alvaro Madrid Aris ◽  
Naoya Fujita ◽  
Masayo Ogawa ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Pediatric Patients ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Initial Evaluation ◽  
Disease Stage ◽  
Evaluation Period ◽  
Uremic Syndrome ◽  
Previously Treated ◽  
Long Acting

Abstract Background Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, a long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report outcomes from a pediatric patient cohort from the ravulizumab clinical trial (NCT03131219) who were switched from chronic eculizumab to ravulizumab treatment. Methods Ten patients received a loading dose of ravulizumab on Day 1, followed by maintenance doses administered initially on Day 15, and then, every 4–8 weeks thereafter, depending on body weight. All patients completed the initial evaluation period of 26 weeks and entered the extension period. Results No patients required dialysis at any point throughout the study. The median estimated glomerular filtration rate values remained stable during the trial: 99.8 mL/min/1.73m2 at baseline, 93.5 mL/min/1.73m2 at 26 weeks, and 104 mL/min/1.73m2 at 52 weeks. At last available follow-up, all patients were in the same chronic kidney disease stage as recorded at baseline. Hematologic variables (platelets, lactate dehydrogenase, and hemoglobin) also remained stable throughout the initial evaluation period and up to the last available follow-up. All patients experienced adverse events; the most common were upper respiratory tract infection (40%) and oropharyngeal pain (30%). There were no meningococcal infections reported, no deaths occurred, and no patients discontinued during the study. Conclusions Overall, treatment with ravulizumab in pediatric patients with aHUS who were previously treated with eculizumab resulted in stable kidney and hematologic parameters, with no unexpected safety concerns when administered every 4–8 weeks. Trial registration Trial identifiers: Trial ID: ALXN1210-aHUS-312 Clinical trials.gov: NCT03131219 EudraCT number: 2016-002499-29

scholarly journals Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anja Gäckler ◽  
Ulf Schönermarck ◽  
Vladimir Dobronravov ◽  
Gaetano La Manna ◽  
Andrew Denker ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Multicenter Trial ◽  
Efficacy And Safety ◽  
Meningococcal Infections ◽  
Phase 3 ◽  
Alternative Complement ◽  
Uremic Syndrome ◽  
Long Acting ◽  
Inhibitor Treatment

Abstract Background Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum. Methods This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 × 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred. Conclusions Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Trial registration Clinical trial identifier:NCT02949128.

Whole-exome sequencing detects mutations in pediatric patients with atypical hemolytic uremic syndrome in Taiwan

2019 ◽  
Vol 494 ◽  
pp. 143-150 ◽  
Author(s):  
Min-Hua Tseng ◽  
Jeng-Daw Tsai ◽  
I-Jung Tsai ◽  
Shih-Ming Huang ◽  
Jing-Long Huang ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Patients ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Whole Exome ◽  
Uremic Syndrome

scholarly journals Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis

2020 ◽  
Author(s):  
Anja Gäckler ◽  
Ulf Schönermarck ◽  
Vladimir Dobronravov ◽  
Gaetano La Manna ◽  
Andrew Denker ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Multicenter Trial ◽  
Efficacy And Safety ◽  
Meningococcal Infections ◽  
Phase 3 ◽  
Alternative Complement ◽  
Uremic Syndrome ◽  
Long Acting ◽  
Inhibitor Treatment

Abstract Background: Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum.Methods: This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 x 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results: Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred.Conclusions: Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Clinical trial identifier: NCT02949128

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