Photo courtesy of the CDC
ORLANDO, FL—In a small study, the cholesterol-lowering medication simvastatin reduced the frequency of vaso-occlusive pain in adults and children with sickle cell disease (SCD).
Overall, there was a 46% decrease in the frequency of vaso-occlusive pain after 3 months of treatment with simvastatin.
There was a slight overall decrease in the intensity of pain as well, but this was not statistically significant.
Still, investigators observed a decrease in biomarkers of inflammation and said the drug appeared to be safe for this patient population.
The team believes these preliminary data suggest the need to conduct a larger, randomized trial of simvastatin in SCD.
Carolyn C. Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California, presented the data at the 2015 ASH Annual Meeting (abstract 545).*
“Vaso-occlusive pain is a clinical hallmark and major cause of morbidity in sickle cell disease,” Dr Hoppe said. “Triggered by polymerization and hemolysis, vaso-occlusion involves multiple pathways.”
Similarly, although statins are best known for their cholesterol-inhibiting ability, they also inhibit oxidative stress and inflammation.
With this in mind, Dr Hoppe and her colleagues previously tested simvastatin in a phase 1 study of SCD patients who were 13 years of age or older.
The investigators found the safety profile to be acceptable, and they observed an improvement in biomarkers of inflammation. So they decided to carry out the current study.
This was a single-center, uncontrolled trial that enrolled SCD patients ages 10 and older. They received once-daily oral simvastatin (40 mg) for 3 months.
The primary outcome measure was the frequency and intensity of vaso-occlusive pain, as recorded by daily electronic pain diaries, before and after simvastatin treatment.
Clinical laboratory studies and plasma biomarkers were evaluated at baseline, at 0.5, 1, 2, and 3 months during treatment, as well as 1 month after the discontinuation of simvastatin.
Results
Nineteen patients completed the study. They had a mean age of 19 (range, 10-34), and 13 were female. Seventeen had HbSS genotype, and 2 had S/β0 thalassemia. Ten patients were receiving hydroxyurea.
The simvastatin adherence rate was 85%, and the adherence to using the daily pain diary was 73%.
Dr Hoppe said there were no new safety issues or drug-related adverse events in this trial. There was no myalgia or myopathy. One subject did experience transient facial swelling that may have been drug-related.
The patients’ total cholesterol decreased by 20% from baseline. There was a significant decrease in both LDL and HDL cholesterol (P<0.001 for both).
Creatinine kinase remained stable during treatment, as did hemoglobin levels.
Dr Hoppe noted that the study was not designed to include an assessment of fetal hemoglobin, so she and her colleagues did not have data on that measure for all the patients, but the team did observe an increase in fetal hemoglobin levels from baseline among the patients who were receiving hydroxyurea.
The investigators observed a decrease from baseline in markers of hemolysis—absolute reticulocyte count (P=0.006) and total bilirubin (P=0.02).
Overall, there was a 46% decrease in the frequency of vaso-occlusive pain from baseline (P=0.005) and a 10% decrease in the intensity of pain (which was not significant).
There was a 59% decrease in hsCRP (P=0.003), an 18% decrease in sE-selectin (P=0.01), a 5% decrease in sICAM (P=0.03), and a 17% decrease in VEGF (P=0.05). There was no significant effect on plasma nitric oxide metabolites, sVCAM1, or P-selectin levels.
“These results are basically preliminary data to give clinical support for a larger, randomized trial of simvastatin to assess its clinical efficacy in SCD,” Dr Hoppe concluded.
She reported receiving research funding and consultancy payments from Eli Lilly and Company, and another investigator involved in this study is an employee of Pharmacyclics LLC.
*Data in the abstract differ from the data presented.