Isturisa best if cortisol returns to normal in saliva, urine: Study
Data from trials show measuring both levels helps patients most
Patients being treated with Isturisa (osilodrostat) for Cushing’s disease see better long-term clinical outcomes when both late-night salivary cortisol and mean urinary free cortisol returned to normal levels, instead of just one or neither of those measures.
Drawing on data from two Phase 3 clinical studies, LINC-3 (NCT0218217) and LINC-4 (NCT02697734), researchers said that’s best to aim for both measures to be normal to see improvements in blood pressure, blood sugar, and quality of life.
“It may be beneficial to measure cortisol levels in both the saliva and the urine in order to evaluate clinical outcomes, as well as to consider aiming for normalization of both of these measurements for the best patient improvement,” the researchers wrote.
The study, “Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol,” was published in the Journal of the Endocrine Society. Isturisa’s clinical program was funded by Novartis, which originally developed the therapy before licensing it to Recordati, which provided support for medical editorial assistance for the study.
In Cushing’s, excess cortisol causes a range of symptoms, including physical changes, such as weight gain, stretch marks, bruising, and muscle loss. It also increases the risk of having high blood pressure, diabetes, obesity, and worse quality of life.
Normal cortisol is main treatment goal
The main goal of treating Cushing’s is to bring cortisol back to normal levels. Doctors can measure cortisol in saliva, sampled late at night, to study its daily patterns, or in urine, to estimate the total amount of cortisol produced by the body over 24 hours or one day.
Isturisa is an oral medication that reduces the cortisol produced by the adrenal glands above the kidneys. In the U.S., it is approved to treat adults with Cushing’s disease for whom pituitary surgery is not curative or not an option. In Europe, it can be used to treat all forms of endogenous Cushing’s syndrome, including Cushing’s disease.
To find out if Cushing’s disease patients have better long-term clinical outcomes if they see both late-night salivary cortisol and mean urinary free cortisol levels return to a normal range with Isturisa, researchers pooled data from 160 patients who took part in LINC-3 and LINC-4. Both trials included 48 weeks of treatment and an optional longer follow-up for patients benefitting from treatment with Isturisa.
At the start of the studies, most patients (85%) had uncontrolled late-night salivary cortisol and mean urinary free cortisol. After 72 weeks, or about 1.4 years, nearly half (48.6%) achieved control of both measures. These patients showed better clinical outcomes than those with just one or no measure controlled.
Patients with both measures controlled had larger reductions in blood pressure than those with only mean urinary free cortisol controlled. In patients with neither measure controlled, blood pressure rose.
Blood sugar and glycated hemoglobin, which can indicate if blood sugar has remained high over the previous months, also improved more when both late-night salivary cortisol and mean urinary free cortisol were controlled, with smaller or no improvements in other groups.
Physical signs of excess cortisol, such as weight, improved in all groups, regardless of control. Quality of life improved the most for patients who had both measures controlled or only mean urinary free cortisol controlled, showing the importance of keeping cortisol under control for overall well-being.
The findings suggest that treatment should focus on controlling both measures for the best clinical outcomes, the researchers said. “Individualized treatment strategies should … include the goal of normalizing both [late-night salivary cortisol and mean urinary free cortisol] while avoiding adrenal insufficiency,” or too-low cortisol, the team wrote.
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