Abstract Body: Introduction: Sickle cell disease causes recurrent vaso-occlusive crises (VOCs) that drive morbidity and healthcare use. Hydroxyurea (HU) is standard therapy, yet many still experience VOCs. Crizanlizumab offers a new option to prevent VOCs. The phase 2 SUSTAIN trial showed reduced VOC rates versus placebo, whereas the phase 3 STAND trial found no significant benefit, leaving uncertainty about its effectiveness in practice. We hypothesized that crizanlizumab (±HU) would have similar annualized VOC rates compared with usual care in real-world practice.
Methods: We conducted a new-user cohort study using electronic health record data from TriNetX (2018–2025). Eligible patients were aged ≥16 years with ≥3 claims for sickle cell disease and ≥12 months of clinical activities. The exposure group included patients initiating crizanlizumab (±HU); the comparator group included those receiving usual care (HU users or HU non-users). The outcome was the annualized rate of VOCs requiring healthcare visits, identified using ICD-10 codes and IV pain medication use. We assigned a pseudo-index date for HU non-users by matching them to the crizanlizumab cohort on demographics. We used stabilized inverse probability of treatment weighting and negative binomial regression to estimate adjusted incidence rate ratios (IRRs).
Results: The study included 891 crizanlizumab users (234 with HU, 657 without HU) and 12,196 usual-care patients (3,255 HU users, 8,941 HU non-users). The mean age was 31 vs. 32 years; 61% were female, and 93% vs. 97% were Black. After weighting, covariates were well balanced. For the primary comparison of crizanlizumab (±HU) vs. usual care, unadjusted VOC rates were 1.62 vs. 0.37 per year; weighted VOC rates were 1.62 vs. 1.52 per year, and the IRR for VOCs was 1.08 (95% CI, 0.82–1.41). For the subgroup comparison of crizanlizumab plus HU vs. HU users, unadjusted VOC rates were 2.20 vs. 0.76 per year; weighted VOC rates were 2.20 vs. 1.60 per year, and the IRR for VOCs was 1.36 (95% CI, 0.89–2.08). For the subgroup comparison of crizanlizumab without HU vs. HU non-users, unadjusted VOC rates were 1.41 vs. 0.23 per year; weighted VOC rates were 1.41 vs. 2.45 per year, and the IRR for VOCs was 0.58 (95% CI, 0.41–0.82).
Conclusions: In this real-world study, crizanlizumab (±HU) showed similar VOC rates to usual care overall. Crizanlizumab with HU showed no added benefit over HU users, while crizanlizumab without HU reduced VOCs compared with HU non-users.