SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.

During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.

“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.

Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.

Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.

Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.

“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.

To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.

The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.

The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.

A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.

Results

The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.

Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.

The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).

The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).

The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).

Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.

The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).

Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).

Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.

*Data in the abstract differ from the presentation and the article.

HU could save millions of lives in Africa, speaker says