Dataset Information

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

ABSTRACT:

Rationale & objective

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS.

Study design

This analysis reports 2-year data from 2 phase 3, single-arm studies.

Setting & participants

One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219).

Exposure

Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight.

Outcomes

The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart.

Analytical approach

All analyses used descriptive statistics. No formal statistical comparisons were performed.

Results

In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m²) and pediatric patients (82.5 mL/min/1.73 m²). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years.

Limitations

Limitations were the small sample of pediatric switch patients and limited availability of genetic data.

Conclusions

Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.

SUBMITTER: Dixon BP

PROVIDER: S-EPMC11298908 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Dixon Bradley P BP Kavanagh David D Aris Alvaro Domingo Madrid ADM Adams Brigitte B Kang Hee Gyung HG Wang Edward E Garlo Katherine K Ogawa Masayo M Amancha Praveen P Chakravarty Sourish S Heyne Nils N Kim Seong Heon SH Cataland Spero S Yoon Sung-Soo SS Miyakawa Yoshitaka Y Luque Yosu Y Muff-Luett Melissa M Tanaka Kazuki K Greenbaum Larry A LA

Kidney medicine 20240614 8

<h4>Rationale & objective</h4>Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS.<h4>Study design</h4>This analysis reports 2-year data from 2 phase 3, single-arm studies.<h4>Setting & participants</h4>One study included C5i-naïve adults (NCT02949128), and the othe ...[more]

PMID: 39105067

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Project description:BackgroundAtypical 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.MethodsThis 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.ResultsEight 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.ConclusionsTreatment 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 registrationClinical trial identifier: NCT02949128 .

Dataset Information

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Rationale & objective

Study design

Setting & participants

Exposure

Outcomes

Analytical approach

Results

Limitations

Conclusions

Publications

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Similar Datasets

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