The risks and benefits of long‐term use of hydroxyurea in sickle cell anemia: A 17.5 year follow‐up

Abstract

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at a 5 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 85:403-408, 2010. V

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Long-term followup from the MSH study that included only adults with severe SCA demonstrated sustained clinical efficacy and 40% lower mortality after 9 years of follow up in participants electing to take hydroxyurea therapy after completion of the trial when compared with those not electing to start hydroxyurea therapy after completing the trial [57]. This survival benefit was maintained at 17.5 years [58]. Another study replicated the benefit of hydroxyurea therapy on survival in a 17-year, open-label trial of 330 adult patients with SCD [59].…”

Intensive management of high‐utilizing adults with sickle cell disease lowers admissions

“…Based on recent data demonstrating improved survival with hydroxyurea use, including patients with milder SCD phenotypes, we recommended hydroxyurea use for all adults without contra-indications or receiving chronic transfusions [17,18]. For those with a high rate of acute care utilization despite hydroxyurea therapy, we recommended a trial of prophylactic transfusions after careful consideration of risks of iron overload and alloimmunization [19].…”

Hydroxyurea in Sickle Cell Disease: Our Experience in Western India

“…Clinically this has correlated with decrease in pain scores and pain crisis per year requiring hospitalization and to some extent BT requirement. Also few studies have followed patients of SCD on Hydroxyurea for periods more than 1 year and are encouraging [25].…”