OBJECTIVES: Sickle cell disease (SCD) is a genetic erythrocyte disorder with limited treatment options. In the past few years, the FDA has approved a monoclonal antibody, crizanlizumab (Nov 15, 2019), and a HbS polymerization inhibitor, voxelotor (Nov 25, 2019), for the treatment of SCD. As newly approved medications become more widely used in real-world clinical practice, it is important to monitor their safety. This study aimed to assess adverse event reports for arthralgia and pain associated with crizanlizumab and voxelotor.

METHODS: FAERS data were analyzed from January 2020 through September 2021. Adverse events reports of arthralgia and pain were assessed separately for voxelotor or crizanlizumab, and each was compared with all other drugs. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and corresponding 95% confidence intervals (CIs) were calculated using SAS OnDemand for academics.

RESULTS: With 16,231 reports of arthralgia, reporting rates for crizanlizumab were significantly higher than with other medications (ROR 6.77, 95% CI 3.34-13.71; PRR 6.58, 95% CI 3.33-13.00). Alternatively, voxelotor was not associated with arthralgia (ROR 0.75, 95% CI 0.50-1.09; PRR 0.76, 95% CI 0.51-1.11). With 85,266 reports of adverse pain events, reporting rates for crizanlizumab were significantly higher than other medications (ROR 15.79, 95% CI 11.97-20.83; PRR 11.28, 95% CI 9.3, 13.67). Reporting rates for voxelotor and pain were also significantly higher than with other medications (ROR 1.38, 95% CI 1.22-1.57; PRR 1.37, 95% CI 1.21- 1.55), though at a lower magnitude than crizanlizumab.

CONCLUSIONS: Our disproportionality analysis identified an association between crizanlizumab and arthralgia, and also with pain. Alternatively, voxelotor was not associated with arthralgia and was weakly associated with pain. Further studies are needed to confirm these findings and to quantify the real-world safety profiles of these newer medications for SCD.