Fact checked byRichard Smith

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July 27, 2023
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Most adults with acromegaly achieve normal IGF-I levels with long-acting pasireotide

Fact checked byRichard Smith
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Key takeaways:

  • Fifty-four percent of adults with acromegaly receiving pasireotide reached an IGF-I level less than or equal to the upper limit of normal.
  • Pasireotide was associated with reductions in tumor diameter and volume.

More than half of adults with acromegaly receiving the somatostatin receptor ligand pasireotide achieved normal insulin-like growth factor I levels, according to data from a long-term real-world study.

“To our knowledge, this analysis, based on our single-center results, reports the longest follow-up of patients with acromegaly treated with pasireotide to date,” Mônica Gadelha, PhD, professor of endocrinology at the medical school of the Universidade Federal do Rio de Janeiro in Brazil, and colleagues wrote in a study published in The Journal of Clinical Endocrinology & Metabolism. “In this cohort, 54% of patients showed IGF-I normalization with pasireotide treatment. Importantly, symptoms of acromegaly improved in the whole cohort and quality of life improved in patients who were controlled.”

The majority of adults with acromegaly achieved normal IGF-1 levels with pasireotide
Data were derived from Gadelha M, et al. J Clin Endocrinol Metab. 2023;doi:10.1210/clinem/dgad378.

Researchers conducted a retrospective single-center study of 50 adults with acromegaly who received pasireotide (Signifor LAR, Novartis) as part of a clinical trial. Adults continued to receive the same dose as they did during the trial, with dose adjustments made at the provider’s discretion. Safety data were collected up to 1 to 3 months after pasireotide discontinuation. Biochemical control was defined as age-adjusted IGF-I less than or equal to the upper limit of normal. Quality of life was assessed through a questionnaire, with a lower score indicating a worse quality of life. Acromegaly symptoms were self-reported by participants as absent, mild, moderate or severe. The first participants received pasireotide in November 2008 and follow-up continued through June 2022.

At the end of the study, 52.9% of adults were still receiving pasireotide, with the remaining participants having discontinued treatment. The study population received pasireotide for a median of 58 months.

Of the group, 54% achieved an IGF-I less than or equal to the upper limit of normal. Normal IGF-I levels were achieved by 30% at 3 months and 28% at 12 months in intention-to-treat analysis. Median IGF-I levels reached 0.7 times the upper limit of normal in adults with controlled IGF-I and 1.8 times the upper limit of normal for those with uncontrolled IGF-I. Median growth hormone decreased to 0.6 ng/mL for adults with controlled IGF-I and 3.6 ng/mL for adults with uncontrolled IGF-I.

The largest tumor diameter shrank from 1.4 cm before pasireotide to 1 cm after treatment (P = .002) among 24 participants with data available. Mean tumor volume decreased from 7.4 cm3 before treatment to 5.7 cm3 after pasireotide (P < .001) among 16 adults with measurements available. Of those 16 participants, 62% had a reduction in tumor volume of more than 25%.

The most severe acromegaly symptoms reported were arthralgia and fatigue. Median symptom scores improved after pasireotide treatment. Quality of life scores were similar for the study group before treatment and after treatment. However, adults who had controlled IGF-I had an increase in quality of life score from baseline to after treatment with pasireotide.

Most adverse events were mild. Of 29 adults with normal ultrasound at baseline, 21% developed biliary sludge and 10% developed cholelithiasis. No deaths were recorded during the study.

Median fasting plasma glucose and HbA1c increased from baseline to 1 month, before declining at 12 months. FPG remained lower than the initial peak long term, whereas HbA1c increased again at the final study visit. The percentage of adults receiving medication for hyperglycemia increased from 38% at baseline to 72% at the final study visit. Most hyperglycemia was managed with concomitant medication.

“Importantly, for patients who initiated antidiabetic medication during treatment with pasireotide, medication was no longer required and glucose and HbA1c levels were normalized following pasireotide discontinuation, supporting the clinical data showing that pasireotide-associated hyperglycemia is reversible upon treatment discontinuation,” the researchers wrote.