Signifor effective in half of Cushing’s disease patients: Study
Treatment efficacy linked to not having diabetes before starting therapy
Treatment with Signifor (pasireotide) normalized urinary cortisol levels in about half of adults with Cushing’s disease, regardless of their gender, a small real-world study suggests.
Because treatment response was associated with the absence of diabetes before treatment, researchers suggest proper blood sugar management in patients planning to start Signifor. The study, “Efficacy and safety of pasireotide in patients with Cushing’s disease: a monocentric experience,” was published in Endocrine.
Cushing’s disease occurs when a tumor on the brain’s pituitary gland makes too much adrenocorticotropic hormone (ACTH). In response, the adrenal glands atop each kidney produce too much cortisol, leading to a hormonal imbalance and various symptoms.
Surgery to remove the tumor is often the first-line treatment for Cushing’s disease, which has an overall cure rate of up to 90%. Patients for whom the surgery fails to cure the disease or who are ineligible for the procedure can take medications to reduce cortisol and ease their symptoms.
Signifor was the first disease-modifying therapy approved for such patients. When injected subcutaneously, or under the skin, its active ingredient, pasireotide, mimics the activity of somatostatin, a naturally occurring hormone that suppresses the release of other hormones, including ACTH. Through this mechanism, Signifor should lower ACTH production, reduce cortisol, and ease symptoms.
Improvements with Signifor treatment
Here, researchers in Italy retrospectively evaluated the efficacy and safety of long-term treatment with Signifor in 19 Cushing’s disease patients (13 women), who’d been referred and followed at the University Hospital of Messina from 2013 to 2023.
Before starting Signifor, all but two patients underwent tumor removal surgery, which wasn’t successful in 12 cases, while the disease recurred in the other five.
With Signifor, over a mean of 21.7 months, 24-hour urinary-free cortisol levels normalized in 10 patients (52.6%) and two also saw their tumor shrink.
Responders also saw significant improvements in several Cushing’s-related parameters, including reduced total cholesterol, triglyceride fats, and low-density lipoprotein (LDL) cholesterol, which is referred to as bad cholesterol. At the same time, levels of HbA1c, an indicator of blood sugar levels over the past two to three months, significantly increased.
Response to the therapy was correlated with younger age at diagnosis, longer disease duration, the absence of diabetes before treatment, and lower Hb1Ac levels.
“Before starting [Signifor] therapy, it is necessary to optimize [blood sugar] treatment in diabetic patients,” the researchers wrote.
No significant difference in treatment response was observed between men and women. Still, men had a significant decrease in total and LDL-cholesterol, and women saw a significant reduction in waist to hip ratio.
The most common adverse events were related to hyperglycemia, or abnormally high blood sugar levels, which led to treatment withdrawal in three cases, without any gender differences. Two patients had an allergic reaction, which led to treatment discontinuation. One patient had adrenal insufficiency, which occurs when the adrenal glands can’t produce sufficient amounts of certain hormones, which was reversed by cutting Signifor’s dose in half. High blood pressure and higher total cholesterol before treatment significantly correlated with adverse events.
“[Signifor] is effective in a significant number of patients with [Cushing’s disease], regardless of gender, having a positive impact on lipid [fat] profile especially in males, and on [body size] parameters in females,” the researchers wrote.
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