Low-dose hydroxycarbamide therapy may offer similar benefit as maximum tolerated dose for children and young adults with sickle cell disease in low-middle-income settings

Abstract

The multiple clinical benefits of hydroxycarbamide in sickle cell disease are supported by a large body of evidence. The maximum tolerated dose (MTD) is the regimen recommended by guidelines from a panel of National Heart, Lung, and Blood Institute (NHLBI) experts, but other dosage regimens have been used in babies (BABY-HUG) 9 to 18 months old (20 mg/kg per day) and developing countries such as India (10 mg/kg per day); however, there has been no direct comparison of the efficacy, effectiveness, or cost-effectiveness of these different regimens. The purpose of this review was to investigate the current situation with various hydroxycarbamide regimens with particular relevance to low-middle-income countries. In regard to methodology, a literature review was undertaken by using multiple databases in PubMed and Google and the search terms included sickle cell disease, hydroxyurea, hydroxycarbamide, sickle cell anaemia, low-middle-income countries, Sub-Saharan Africa, and India. Although MTD regimens have been widely used in research, especially within North America, clinical trials elsewhere tend to use fixed-dose regimens. In a survey of haematologists across Europe and Africa, 60% (75% response rate) did not use the MTD regimen for hydroxycarbamide treatment of sickle cell disease. The recommendations are (1) for practical purposes to commence using fixed-dose hydroxycarbamide in line with BABY-HUG recommendations and then (2) to consider or propose a trial comparing MTD escalation with various fixed doses and to include as end points health-related quality of life, haemoglobin F levels, adherence, and cost-effectiveness.

Sickle Cell Disease—Genetics, Pathophysiology, Clinical Presentation and Treatment

“…In adults, indications for hydroxycarbamide may include [ 66 , 67 , 68 ]: Frequent painful episodes (>3 per annum) or chronic debilitating pain not controlled by usual protocols. History of stroke or a high risk for stroke or other severe vaso-occlusive events.…”

Hydroxyurea in children with sickle cell disease in a resource‐poor setting: Monitoring and effects of therapy. A practical perspective

“…No major side effects were reported, thus adding to other reports from Nigeria 20,21,35 of no deleterious effects of host or environmental factors on the safety of HU in Africans. Reports from Africa 24,36–39 and India 40 have also demonstrated clinical and laboratory response to low and moderate fixed doses of HU in adults and children with SCD. However, the NOHARM 41 trial reported that an MTD escalation of HU to 30 mg/kg/day, in Ugandan children with SCD, produced superior clinical and laboratory efficacy compared to a fixed dose regime of 20 mg/kg/day, without any increase in toxicity.…”

Hydroxyurea in children with sickle cell disease in a resource-poor setting: Monitoring and effects of therapy. A practical perspective

“…Our focus is on achieving good clinical response without overly intensive dose escalation 39 . Researchers in Africa and Asia are reporting effectiveness of intermittent 40 or low-fixed dosing 35,41 of HU in SCD subjects. In Nigeria, Titilola 42 reported clinical and laboratory response to a low fixed dose of HU in adult patients with SCD.…”