LANREOTIDE is an effective drug for the treatment of acromegaly
Introduction
Acromegaly, a rare disease resulting from a pituitary adenoma, is typically characterized by an increase in the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), which lead to various symptoms. Heart and vascular diseases, diabetes mellitus, bone and joint diseases, and sleep apnea commonly affect patients with this condition - these disorders also contribute to an increase in mortality [2].
Medical professionals often recommend treatment when it's not possible to completely remove adenomas or when surgical treatment isn't an option or the patient declines it [1]. For such patients, somatostatin analogs given over an extended period typically serve as the first-line treatment [3, 4]. Lanreotide, one such analog, has demonstrated its effectiveness in reducing GH and IGF-1 concentrations along with the volume of pituitary adenomas, consequently decreasing symptoms and improving quality of life [5–7].
The recommended therapeutic indications for lanreotide include the long-term treatment of acromegaly in cases where the levels of GH and/or IGF-1 in the blood don't normalize post-surgery and/or radiotherapy, or when surgical treatment and/or radiotherapy are unsuitable [11]. The treatment can also help alleviate symptoms of acromegaly.
Treatment with somatostatin analogs often leads to biochemical remission and a decrease in mortality [8]. Given the need for long-term treatment, the convenience of drug formulation is crucial. Lanreotide, available in prefilled syringes, allows for self-administration by patients.
Upon administration every four weeks, a pharmacologically effective concentration of lanreotide is achieved [9]. However, studies suggest that some patients could receive treatment every 6–8 weeks [10, 11]. The Lanreotide Extended Autogel Duration (LEAD) study is one such example [12].
LEAD is a large international clinical trial that aimed to evaluate the safety, effectiveness, and clinical outcomes of administering lanreotide (Somatuline Autogel®) to acromegaly patients previously treated with 120 mg of octreotide LAR 10 mg or 20 mg.
The Structure of the LEAD Study
The study was conducted in two phases. The initial phase involved the administration of 5 injections of lanreotide 120 mg at six-week intervals. The second phase's dosing schedule was adjusted depending on the IGF-1 levels at the end of phase one, with the drug administered every 4, 6, or 8 weeks accordingly. Patients with an IGF-1 concentration that exceeded the normal range by over 130% at the end of phase one were disqualified from the study. In the first phase, 124 patients participated, out of which 15 discontinued their participation.
During the second phase, a total of 109 patients participated, and 107 completed the phase. Across different groups, the primary characteristics of the patients were pretty similar. But, a slightly higher number of women were present in the group that received the drug every 8 weeks.
Analysis of Octreotide Treatment and IGF-1 Concentration
On average, patients had been treated with octreotide LAR for 2.5 years preceding the study, with 80.5% of patients having received a 20 mg dosage. In the primary analysis, 94 out of the 124 patients (75.8%) who received treatment every 6 or 8 weeks attained normal IGF-1 concentrations following 48 weeks.
Further examination of the secondary objectives revealed that 110 out of 124 (88.7%) patients achieved normal IGF-1 concentrations after 24 weeks. It was observed in patients who received treatment every 6 weeks at the conclusion of the first phase. Among patients who had the lengthiest treatment duration (administered every 8 weeks), 25 out of 124 (20.2%) attained normal IGF-1 concentration after 48 weeks.
Upon assigning dosing intervals individually, all 13 patients receiving the drug every 4 weeks achieved normal IGF-1 concentrations after 48 weeks, as did 67 out of 70 (96%) patients when administered every 6 weeks, and 25 out of 26 (96%) patients when given every 8 weeks.
Achievement of GH Control and Symptom Assessment
The LEAD study demonstrated that most patients could regulate their GH levels effectively, maintaining a GH concentration of <2.5 μg/l along with a normal IGF-1 concentration after receiving 24 weeks of treatment every six weeks during the trial's first phase. Available data for 112 patients showed that 105 patients regulated their GH concentration to <2.5 μg/l and 103 patients managed to normalize both their GH and IGF-1 concentrations. Observations from the initial phase indicated that most patients obtained remarkably low GH concentrations.
No matter the administration frequency, GH concentration levels presented relative stability, particularly noticeable when the drug therapy occurred every six weeks. Changes in acromegaly symptoms seemed minimal, according to the findings from the PASQ questionnaire.
Researchers assessed the AcroQoL questionnaire results, utilized as an additional tool encompassing the severity of acromegaly, at three different times: at the start, midway point (24 weeks), and end (48 weeks) of the study. This assessment did not highlight any significant differences between the dosage intervals. Among the group of patients, 91 out of 124 (73.4%) reported experiencing adverse reactions. These reactions did not exhibit any differences across the various dosage interval groups or between the study's two phases. The most commonly reported adverse reactions included cholelithiasis (11.3%) and diarrhea (10.5%).
Summary
A significant improvement in good biochemical control has been achieved by treating with lanreotide (Somatuline Autogel®), both every 6 and every 8 weeks for patients previously treated with octreotide LAR at doses of 10 mg or 20 mg every 4 weeks. Such treatment with longer intervals of lanreotide administration is an alternative for patients who have successfully achieved good disease control with octreotide LAR.
Supplement to the journal INTERNIST, ENDOCRINE DISEASES UPDATE.
