Patients with sickle cell disease (SCD) exhibited a decrease in vaso-occlusive crises (VOC) when using l-glutamine or crizanlizumab, while voxelotor helped improve hemoglobin concentrations, according to a study published in Cureus.

A systematic review of 12 studies looked into the effects of l-glutamine, crizanlizumab, and voxelotor on patients with SCD regarding their efficacy, response, complications, and safety. Studies were from 2017 through 2021 and were identified using the Cochrane Library,, and Additionally, the review evaluated the possible safe, effective, and tolerable combinations of these 3 drugs for SCD.

L-glutamine was shown to decrease the number of VOC pain crises, acute SCD complications, and hospitalizations and lowered emergency department visits, given the reduction of uncomplicated VOCs and increased hemoglobin levels.

On the other hand, voxelotor also proved to raise hemoglobin levels which in return increased oxygen capacity, as well as reduced unconjugated bilirubin levels, the number of VOC pain crises and hospital days, and overall improved the quality of life of patients. Finally, crizanlizumab showed an increase in the median time between the first and second VOC pain crisis and prevented the adhesion of sickle red blood cells to the vascular endothelium.

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Regarding combination therapy, the study concluded that pairing voxelotor and l-glutamine had the most meaningful health benefits reported in the studies. Moreover, the combination of voxelotor and l-glutamine resulted in acceptable adverse effects with low toxicity levels.

“Based on the dose-effect-based strategy via the Loewe Additivity model, SCD patients may achieve greater benefit from an l-glutamine plus voxelotor combination therapy than monotherapy of l-glutamine, voxelotor, or crizanlizumab,” the authors wrote.

The 3 drugs did not prove to reduce the use of analgesics and opioids for pain management during VOC crises.

The impact of these new medications on VOC events may improve the standard of care and overall quality of life in SCD patients, which the authors said is a necessity long overdue for these patients. Nevertheless, future studies should further analyze the advantages and disadvantages of combining these drugs, they wrote.


Dick M, Abdelgadir A, Kulkarni V, et al. Comparing the safety and efficacy of l-glutamine, voxelotor, and crizanlizumab for reducing the frequency of vaso-occlusive crisis in sickle cell disease: a systematic review. Cureus. Published online May 11, 2022. doi:10.7759/cureus.24920