Image by Betty Pace
A sickled red blood cell beside a normal one
Crizanlizumab can reduce vaso-occlusive crises (VOCs) across subgroups of patients with sickle cell disease (SCD), according to a post-hoc analysis of the phase 2 SUSTAIN trial.
Researchers found crizanlizumab was more effective than placebo at delaying time to first VOC and eliminating crises in patients who had numerous previous crises, exhibited the HbSS genotype, or were taking concomitant hydroxyurea.
Abdullah Kutlar, MD, of the Medical College of Georgia in Augusta, and his colleagues reported these findings in the American Journal of Hematology.
The phase 2 SUSTAIN trial previously showed that crizanlizumab—a humanized, anti–P-selectin monoclonal antibody—reduced the frequency of VOCs by 45% and delayed time to first crisis by about 3 months.
Additionally, a subgroup analysis showed there was a lower frequency of VOCs with crizanlizumab at 5 mg/kg, compared with placebo, regardless of the number of prior VOCs, concomitant hydroxyurea use, or the SCD genotype.
The present post-hoc analysis took a deeper look at these observations across the same subgroups. Specifically, the investigators assessed elimination of VOCs, time to first crisis, and adverse events in 132 patients.
Crizanlizumab eliminated VOCs about seven times more frequently than did placebo in patients who had a high frequency of VOCs before the study (5 to 10 VOCs in the year prior)—28.0% and 4.2%, respectively.
Crizanlizumab eliminated VOCs about twice as often as placebo in patients with the HbSS genotype—31.9% and 17.0%, respectively—and in patients who were using concomitant hydroxyurea—33.3% and 17.5%, respectively.
Further analysis showed that crizanlizumab delayed time to first VOC across all subgroups.
In patients with the HbSS genotype, the time to first VOC was 4.07 months with crizanlizumab and 1.12 months with placebo.
In patients with a higher frequency of previous VOCs, the time to first on-study VOC was 2.43 months with crizanlizumab and 1.03 months with placebo.
In patients taking hydroxyurea, the time to first VOC was 2.43 months with crizanlizumab and 1.45 months with placebo.
Safety was comparable across subgroups.
This study was sponsored by Novartis. The authors reported financial relationships with Novartis, Bluebird Bio, AstraZeneca, and others.