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Celebrating Diversity Within the Sickle Cell Community: Commitment, Innovation, Practice
Friday, October 12 • 3:45pm - 4:00pm
Crizanlizumab 5.0 Mg/Kg Increased the Time to First On-Treatment Sickel Cell Pain Crisis (SCPC) and the Likelihood of not Experiencing SCPC While on Treatment: Subgroup Analyses of the Phase 2 Sustain Study

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Abstract

Authors:
Dr. Julie Kanter, Division of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA , Dr. Abdullah Kutlar, Sickle Cell Center, Medical College of Georgia, Augusta University, Augusta, Georgia, US, Dr. Darla Liles, Division of Hematology–Oncology, East Carolina University, Greenville, North Carolina, USA , Dr. Rodolfo Cancado, Department of Hematology–Oncology, Santa Casa Medical School of São Paulo, São Paulo, Brazil, Dr. Andreas Bruederle,  Novartis Pharma AG, Basel, Switzerland, Dr. Michael Shi, Novartis Pharma AG, Basel, Switzerland, Dr. Zewen Zhu, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA, Dr. Kenneth Ataga, Division of Hematology–Oncology, University of North Carolina, Chapel Hill, North Carolina, USA , Dr. Menaka Bhor, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA        

Objective: In the 52-week SUSTAIN study, crizanlizumab 5.0 mg/kg significantly reduced frequency of SCPCs versus placebo (1.6 vs 3.0, P=0.01) and increased time to first on-treatment SCPC (4.1 vs 1.4 months, P=0.001) in patients with sickle cell disease (SCD). Objectives of this study included evaluating time to first SCPC in patient subgroups and likelihood of not experiencing SCPC for the duration of the trial using post hoc analyses.
Methods: SUSTAIN was a randomized, double-blind, placebo-controlled, phase 2 study (NCT01895361). Inclusion criteria were: SCD patients aged 16-65 years; 2-10 SCPCs in previous 12 months; concomitant hydroxyurea use permitted if ≥6 months and stable dose for ≥3 months. Patients were randomized 1:1:1 to receive intravenous crizanlizumab 5.0 mg/kg, 2.5 mg/kg, or placebo. Study treatments were administered on days 1 and 15, then every 4 weeks to week 50, with the final assessment at week 52. Median time to first SCPC after first dose was summarized for crizanlizumab 5.0 mg/kg or placebo in these subgroups: 2-4 or 5-10 SCPCs in previous 12 months; SCD genotype; and hydroxyurea use at baseline. Hazard ratios (HRs) for crizanlizumab 5.0 mg/kg versus placebo were calculated based on Cox regression analysis, with treatment as a covariate. Descriptive statistics were used to summarize frequency of patients who were SCPC event-free for the duration of the study by prior SCPC events, SCD genotype, and hydroxyurea use at baseline.
Results: 67 patients received crizanlizumab 5.0 mg/kg and 65 received placebo. There was a meaningful delay in time to first SCPC with crizanlizumab 5.0 mg/kg versus placebo observed in the entire study population. The effect was present in both SCPC subgroups, and the largest treatment difference was observed in HbSS SCD versus other genotypes (4.1 vs 1.1 months; HR: 0.50). In patients taking hydroxyurea who experienced 2-10 SCPCs in the previous year, time to first on-study SCPC was longer with crizanlizumab 5.0 mg/kg versus placebo (2.4 vs 1.2 months; HR: 0.58). A greater proportion of patients treated with crizanlizumab 5.0 mg/kg were SCPC event-free versus placebo in each of the analyzed subgroups. One third of patients who were taking hydroxyurea and treated with crizanlizumab 5.0 mg/kg were SCPC event-free during the study versus 17.5% with placebo, possibly suggesting an additive effect.  
Conclusions: With crizanlizumab 5.0 mg/kg, there was a clinically meaningful delay in time to first SCPC and an increased likelihood of being SCPC-free versus placebo in all subgroups investigated, including patients taking hydroxyurea who had still experienced 2-10 SCPCs in the previous year, indicating that P-selectin inhibition provided additional beneficial treatment effect compared with hydroxyurea alone.



         
       
       
     
         
     
       
       


Speakers
avatar for Julie Kanter, MD

Julie Kanter, MD

Lifespan Hematologist, Medical University of South Carolina
Dr. Julie Kanter is a lifespan hematologist specializing in sickle cell disease.  She is an associate professor of Pediatrics at the Medical University of South Carolina and runs the first all-ages, Lifespan Comprehensive Sickle Cell Center.  Dr. Kanter works closely with national... Read More →


Friday October 12, 2018 3:45pm - 4:00pm
Constellation C

Attendees (15)