An authoritative review article in the December 2014 edition of Blood, the Journal of the American Society of Haematology, makes a compelling case to increase use of hydroxycarbamide among patients with sickle cell disease. Hydroxycarbamide (or hydroxyurea) remains the only treatment proven to be effective in sickle cell. Since the publication by Dr Sam Charache in 1995 of the results of the clinical trial documenting it’s effectiveness, the drug has been in regular use, although only in a minority of patients. There remains considerable resistance to it’s use among patients and at the moment perhaps only about 10% of patients are taking hydroxycarbamide.
The authors of the current study reviewed the results of 48 studies on the use of hydroxycarbamide in sickle cell, published between 2007 and 2013. They confirmed that hydroxycarbamide has clear beneficial effects: (1) it reduces the number of painful crises, (2) it prevents attacks of the acute chest syndrome, (3) it reduces the need for blood transfusions, (4) it reduces the number of hospital admissions and (5) it improves life expectancy.
Whether hydroxycarbamide reduces organ damage, such as to the spleen, kidneys or lungs and whether it can prevent strokes was less clear cut and the evidence that it is helpful in patients with Hb SC disease or Hb S-beta thalassaemia was also not as good. Nevertheless, the substantial benefits documented in patients with Hb SS disease are very consistent.
Importantly, in terms of side effects, the authors of the review found no evidence of any serious concerns. The commonest side effect were low blood counts (anaemia or a low white cell or platelet count). These complications were trivial, picked up by regular blood tests and easily corrected by temporarily stopping the drug and reducing the dose. They found no evidence that long term consumption of hydroxycarbamide caused an increased risk of cancer and no evidence for any reduction in fertility or risk of babies being born with congenital malformations, if either the mother or father were taking the drug at the time of conception or during pregnancy. These findings are very reassuring.
In view of the serious nature of sickle cell, and because of the proven benefits of hydroxycarbamide and lack of any serious side effects the authors made recommendations for significantly increasing the number of patients offered treatment with hydroxycarbamide. These recommendations are in broad agreement with other recently published guidelines. Treatment with hydroxycarbamide is recommended for patients with (1) three or more moderate or severe painful crises a year, (2) a history of the acute chest syndrome or symptomatic anaemia and (3) a previous stroke, if they are unable to have blood transfusions on a regular basis.
As noted above only about 10% of patients take hydroxycarbamide at the moment and, of these, we know that only about one third take the tablets as prescribed. If the potential of this valuable drug is to be fully realised we need to dramatically increase the number of patients who are willing use hydroxycarbamide and who will take it regularly every day. How to do this successfully remains as elusive as ever but clearly must start with an educational campaign making sure that everyone understands the benefits of the drug.
Update on the use of hydroxyurea therapy in sickle cell disease. TE Wong, AM Brandow, W Lim & R Lottenberg. Blood, volume 124, pages 3850-3857, December 2014