In the JournalsPerspective

One-third of adults with acromegaly make medication dosing errors

A real-world analysis of adults with acromegaly suggests that most patients prescribed the growth hormone blocker pegvisomant take the drug as directed but that one-third make critical dosing errors, potentially affecting disease control, according to findings published in Pituitary.

“Pivotal studies in patients with acromegaly treated with pegvisomant showed efficacy rates of 90%,” Laura Sanchez-Cenizo, PhD, a medical adviser with Pfizer in Madrid, and colleagues wrote in the study background. “However, data from observational studies showed that long-term effectiveness in a normal clinical setting could be lower (67%), which may be related to an insufficient dose titration, poor patient compliance or to inadequate reconstitution and/or administration of treatment.”

Sanchez-Cenizo and colleagues analyzed data from 108 patients with acromegaly prescribed pegvisomant (Somavert, Pfizer) therapy for at least 12 months participating in PEGASO, an observational, cross-sectional study conducted during endocrinology consultations in acromegaly referral hospitals in Spain (60.2% women; mean age, 55 years; mean disease duration, 11.3 years). Researchers used clinical records to review acromegaly history and comorbidities and assessed insulin-like growth factor I levels to determine acromegaly control. Patient adherence to treatment was assessed via two validated questionnaires and a prescription record review. Researchers asked study participants to simulate the preparation and administration of pegvisomant as they normally would at home and noted potential errors in the process.

Within the cohort, 52% presented with at least four comorbid conditions, and 85% had undergone pituitary surgery before pegvisomant treatment. Mean duration of pegvisomant treatment was 5.9 years, and mean daily dose was 15.2 mg per day, with 60.2% of patients administering pegvisomant daily and 39.8% following alternative dosing schedules, according to researchers.

Researchers found that 90.6% of patients were adherent to pegvisomant treatment, and 72.2% of patients presented with controlled acromegaly as measured by IGF-I levels. According to questionnaire data, patients overall reported high satisfaction and convenience with the treatment.

After observing patient administration of treatment, the researchers found that 34.3% made at least one mistake at some phase of the reconstitution/administration procedure. Among mixing mistakes, 10.8% made errors during steps 4 through 6, including diluent collection and injection of diluent into the pegvisomant vial, which researchers defined as “critical steps.”

In assessing administration errors, researchers found that 4.9% of patients made mistakes regarding choice of injection site, and 7.8% of patients made mistakes in the steps of needle introduction and injection, also considered critical.

The proportion of patients with controlled acromegaly was numerically but not significantly lower in the group of patients observed making dosing errors vs. those who did not (62.9% vs. 74.6%), according to researchers. Those who did not correctly mix the medication presented a poorer control of symptoms as measured by the Patient-Assessed Acromegaly Symptom questionnaire score (mean score, 23 vs. 16.7; P = .037).

The researchers noted that patients willing to participate in the study may be more adherent to treatment vs. patients who declined participation, whereas patients who abandoned treatment before 12 months, possibly for reasons related to adherence, were not included in the study.

“Correct administration of medication is part of patient adherence to treatment, and therefore, effective training by the clinician is essential,” the researchers wrote. “Adherence should be monitored as well as dosing compliance in order to improve the effectiveness of pegvisomant in real-world clinical practice.” – by Regina Schaffer

Disclosures: Pfizer funded the PEGASO study and provided medical writing support. Sanchez-Cenizo reports she is an employee of Pfizer. Please see the study for all other authors’ relevant financial disclosures.

A real-world analysis of adults with acromegaly suggests that most patients prescribed the growth hormone blocker pegvisomant take the drug as directed but that one-third make critical dosing errors, potentially affecting disease control, according to findings published in Pituitary.

“Pivotal studies in patients with acromegaly treated with pegvisomant showed efficacy rates of 90%,” Laura Sanchez-Cenizo, PhD, a medical adviser with Pfizer in Madrid, and colleagues wrote in the study background. “However, data from observational studies showed that long-term effectiveness in a normal clinical setting could be lower (67%), which may be related to an insufficient dose titration, poor patient compliance or to inadequate reconstitution and/or administration of treatment.”

Sanchez-Cenizo and colleagues analyzed data from 108 patients with acromegaly prescribed pegvisomant (Somavert, Pfizer) therapy for at least 12 months participating in PEGASO, an observational, cross-sectional study conducted during endocrinology consultations in acromegaly referral hospitals in Spain (60.2% women; mean age, 55 years; mean disease duration, 11.3 years). Researchers used clinical records to review acromegaly history and comorbidities and assessed insulin-like growth factor I levels to determine acromegaly control. Patient adherence to treatment was assessed via two validated questionnaires and a prescription record review. Researchers asked study participants to simulate the preparation and administration of pegvisomant as they normally would at home and noted potential errors in the process.

Within the cohort, 52% presented with at least four comorbid conditions, and 85% had undergone pituitary surgery before pegvisomant treatment. Mean duration of pegvisomant treatment was 5.9 years, and mean daily dose was 15.2 mg per day, with 60.2% of patients administering pegvisomant daily and 39.8% following alternative dosing schedules, according to researchers.

Researchers found that 90.6% of patients were adherent to pegvisomant treatment, and 72.2% of patients presented with controlled acromegaly as measured by IGF-I levels. According to questionnaire data, patients overall reported high satisfaction and convenience with the treatment.

After observing patient administration of treatment, the researchers found that 34.3% made at least one mistake at some phase of the reconstitution/administration procedure. Among mixing mistakes, 10.8% made errors during steps 4 through 6, including diluent collection and injection of diluent into the pegvisomant vial, which researchers defined as “critical steps.”

In assessing administration errors, researchers found that 4.9% of patients made mistakes regarding choice of injection site, and 7.8% of patients made mistakes in the steps of needle introduction and injection, also considered critical.

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The proportion of patients with controlled acromegaly was numerically but not significantly lower in the group of patients observed making dosing errors vs. those who did not (62.9% vs. 74.6%), according to researchers. Those who did not correctly mix the medication presented a poorer control of symptoms as measured by the Patient-Assessed Acromegaly Symptom questionnaire score (mean score, 23 vs. 16.7; P = .037).

The researchers noted that patients willing to participate in the study may be more adherent to treatment vs. patients who declined participation, whereas patients who abandoned treatment before 12 months, possibly for reasons related to adherence, were not included in the study.

“Correct administration of medication is part of patient adherence to treatment, and therefore, effective training by the clinician is essential,” the researchers wrote. “Adherence should be monitored as well as dosing compliance in order to improve the effectiveness of pegvisomant in real-world clinical practice.” – by Regina Schaffer

Disclosures: Pfizer funded the PEGASO study and provided medical writing support. Sanchez-Cenizo reports she is an employee of Pfizer. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Marcello D. Bronstein

    Marcello D. Bronstein

    These findings do not surprise me. Pegvisomant is not the first-line therapy for acromegaly. This drug is reserved for patients with resistance to somatostatin analogues. Theoretically, 100% of these patients with acromegaly should experience disease control with pegvisomant therapy, as it is a very efficacious drug for normalizing IGF-I levels. In real life, however, there are drawbacks to this therapy that can interfere with the results. Not all patients are properly instructed in how to use the injection. Due to this, some patients make mixing and injection mistakes. Many also forget to take the drug as prescribed, particularly those who are prescribed the therapy once or twice a week vs. daily injection. Some also complain of a painful sensation from the needle, which is something that needs to be improved with this drug.

    Additionally, many patients with acromegaly don’t feel that bad. It is like having a high LDL cholesterol level — that is not a symptom you can feel, and that can affect adherence.

    In every center, we need a nurse or other health care professional who can properly instruct the patient in how to inject the drug and mix the therapy. We must inform the patient that even if he or she does not feel bad, acromegaly is a terrible disease that, as time goes by, will increase the risk for CVD and even cancer. This can be a “silent” disease, and therefore, patients need treatment.

    • Marcello D. Bronstein, MD, PhD
    • Professor of Endocrinology,
      Chief, Neuroendocrine Unit,
      Division of Endocrinology and Metabolism
      Hospital das Clinicas, University of Sao Paulo

    Disclosures: Bronstein reports he has received speaking fees from Ipsen and Novartis, serves on advisory boards for Chiasma Pharma, Ipsen and Novartis and is a principal investigator for clinical trials for Ipsen and Novartis.