Engineered monoclonal antibody proteins that often bind to T cells or other structures to modify disease called “mabs” because their name ends with it – are becoming popular. Crizanlizumab was engineered to bind to anti-P-selectin as a monoclonal antibody. 28% were event free on the medication versus 4.2% on placebo. Worse cases (high prior number of vaso-occlusive crisis, concomitant hydrourea, and/or HbSS genotype benefited most.
Am J Hematol. 2019 Jan;94(1):55-61. doi: 10.1002/ajh.25308.
Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell
disease: A SUSTAIN study analysis.
Kutlar A et al
https://www.ncbi.nlm.nih.gov/pubmed/30295335
- crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks; 41-45 cases in each group
- 14 times over 52 weeks meant 2 loading doses in the first month followed by monthly infusions thereafter
- 2.5 mg was not good enough and not even included in analysis
Results: – you can see how those with more prior events did better
- they felt “the positive effects are at least partially through increased fetal hemoglobin and alteration of nitric oxide within RBC”
Side effects:
- “No hepatic or splenic sequestration events were reported among patients in either
the crizanlizumab 5 mg/kg or placebo arms.” -
buried in a table not included in the actual report was fact that 21/146 had side effects; 11 were severe and serious – NO mention was made on what they were – I cannot imagine a reviewer allowing this past him/her – I would have that reviewer fired!
- I have asked one of the authors for information re above.
They do mention an alternative – L-Glutamine orally:
Niihara, Yutaka, et al.
A phase 3 trial of L-glutamine in sickle cell disease.
New England Journal of Medicine 379.3 (2018): 226-235
https://www.childrenshospitaloakland.org/Uploads/Public/Documents/Media/NEJMoa1715971.pdf
- l-glutamine powder or placebo powder (100% maltodextrin), administered orally
twice daily at approximately 0.3 g per kilogram of body weight per dose (10 g, 20 g, or 30 g [maximum dose] per day), followed by a tapering period of 3 weeks and an observation period of 2 weeks (total trial duration, 53 weeks)
results:
Comment – am awaiting info on side effects before commenting
