Crizanlizumab’s Role in Reducing Vaso-Occlusive Crises and Opioid Use in SCD

Vaso-occlusive crises (VOCs) are a major burden for individuals living with sickle cell disease (SCD), often causing frequent emergency visits, hospitalizations, and significant opioid use for pain management. Despite the availability of hydroxyurea (HU) as a standard disease-modifying therapy, many patients continue to experience recurrent crises and associated complications. The need for alternative therapeutic options has prompted investigation into targeted treatments such as crizanlizumab, a monoclonal antibody that inhibits P-selectin, a key mediator of cell adhesion involved in vaso-occlusion.

A study published in February 2025 in the European Journal of Haematology provides valuable real-world evidence of crizanlizumab’s effectiveness in reducing VOC frequency and opioid use over 12 months. This analysis was conducted through a global managed access program (MAP) that provided pre-approval access to patients with severe SCD who were ineligible for clinical trials or lacked alternative treatment options.

Here's a brief overview of the study, its results, and its clinical implications.

Study Design and Patient Profile

The analysis included 112 patients with confirmed SCD aged 16 to 70 years who completed 12 months of treatment with crizanlizumab (5 mg/kg, intravenously). Participants were recruited from Brazil, Italy, Spain, Canada, and Israel. Eligible patients had confirmed SCD of any genotype and a history of recurrent VOCs despite preventive therapies such as HU, L-glutamine, or erythropoietin-stimulating agents. Concurrent HU use was reported in 73.7 percent of patients.

Importantly, 85.7 percent of patients had been hospitalized for SCD-related complications in the year before enrollment, underscoring the severity of disease in this population.

Reduction in Vaso-Occlusive Crises

Looking at the results, over 12 months, treatment with crizanlizumab led to marked reductions in both home- and healthcare-managed VOCs.

• Home-managed VOCs: The proportion of patients experiencing at least one home-managed VOC decreased from 99.1 percent to 81.3 percent, with a median reduction of 3.0 events over 12 months (IQR: −6.0, −1.0).
• Healthcare-managed VOCs: The proportion of patients requiring a healthcare visit for a VOC dropped from 93.8 percent to 59.8 percent, with a median reduction of 2.0 events (IQR: −4.0, 0).

Similar reductions were observed across SCD genotypes and regardless of prior HU use, indicating broad therapeutic potential.

Lower Opioid Use

Crizanlizumab was also associated with a 35.5 percent reduction in opioid use for VOC-related pain. At the start of the study, 95.5 percent of patients required opioids to manage their pain. After 12 months of treatment, this number dropped to 61.6 percent. Morphine was the most prescribed, followed by tramadol and codeine. Frequency of opioid use shifted toward more infrequent dosing, reflecting improved pain control.

Safety Profile

Adverse events (AEs) occurred in 51.8 percent of patients, consistent with prior clinical trial data. The most common AEs included SCA with VOC at 17 percent, general pain at 13.4 percent, fever at 11.6 percent, arthralgia at 7.1 percent, and extreme pain at 5.4 percent. Infusion-related reactions were reported in three patients, or three percent, leading to discontinuation in two cases. Ten deaths occurred during the study, none of which were attributed to crizanlizumab.

Implications for Clinical Practice

These real-world findings align closely with the pivotal SUSTAIN trial, which demonstrated a 45.3 percent reduction in annual VOC rates versus placebo. The rate of home-managed VOCs was nearly double the rate of hospital-managed events. This highlights a potential underestimation of true VOC frequency in routine clinical practice. The reduction in opioid use is particularly meaningful given concerns about dependency, side effects, and healthcare costs. Unlike controlled trial settings, this MAP reflects treatment outcomes in diverse healthcare environments, strengthening the external validity of crizanlizumab’s benefits.

Reference: 

DeBonnett L, Joshi V, Silva-Pinto AC, et al. Real-World Evidence of Crizanlizumab Showing Reductions in Vaso-Occlusive Crises and Opioid Usage in Sickle Cell Disease. Eur J Haematol. 2025;114(2):293-302. doi:10.1111/ejh.14323