12200 Impact Of Strict IGF-1 Control (I-Con) On Quality Of Life Scores In Patients With Acromegaly

Abstract Disclosure: C. Gandhi: None. C.L. Chik: Advisory Board Member; Self; Ipsen, Novo Nordisk, Novartis Pharmaceuticals. Grant Recipient; Self; Pfizer, Inc.. J.A. Rivera: None. M. Denis: None. S. Van Uum: Advisory Board Member; Self; Ipsen, Pfizer, Inc., Novo Nordisk, Spruce. D.T. Holmes: Other; Self; Roche Diagnostics. S.Z. Ezzat: Advisory Board Member; Self; Bayer, Inc., Eli Lilly & Company, Ipsen, Novartis Pharmaceuticals, Merck, Eisai. Objective: Examine, in a real world setting, whether strict normalization of modestly elevated IGF-1 can result in clinical and health-related quality of life benefits in patients with acromegaly in a prospective 6-month multicenter interventional study. Methods: Strict IGF-1 control was achieved by the addition or dose optimization of pegvisomant (PEGV) in acromegaly patients with modest elevation of IGF-1 levels (>100% and <150% of upper limit of normal [%ULN]). IGF-1 measurements were completed in a designated central laboratory, initially using the IDS-iSYS and after the first four patients with the Roche Elecsys® method. The transition did not impact study results. Clinical and biochemical parameters were assessed at baseline, 1 and 3 months for dose titration of PEGV and at 6 months. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), the Acromegaly Quality of Life questionnaire (AcroQoL) and the Acromegaly Disease Activity Tool (ACRODAT®) were completed at baseline and at 6 months. Results: Ten patients (8 males, mean age at screening 50.7 ± 11.3 years) from four centers across Canada participated in the study. Age at diagnosis was 43.9 ± 12.1 years and all patients had macrotumors. Nine patients had prior transsphenoidal surgeries including one with adjunct radiation therapy. All 10 patients had trials of somatostatin analogs (SSA) and SSA was switched to PEGV in two patients because of lack of efficacy. At the time of screening, six patients were on SSA, two on PEGV, and two on SSA and PEGV. At six months, the mean daily dose of PEGV increased from 7.5 ± 12.3 mg (range 0 to 30 mg daily) to 17.6 ± 13.7 mg (range 5 to 40 mg daily). After six months of dose escalation or the addition of PEGV, IGF-1 decreased from 258.5 ± 59.2 µg/L (121.8 ± 14.4 %ULN) to 184.1 ± 41.1 µg/L (86.6 ± 20.0 %ULN) (p=0.001). The summation of PASQ1 to PASQ6 score decreased from 14.6 ± 10.7 to 11.1 ± 8.9 (p=0.02); however there was no statistically significant difference in the AcroQoL score (63.8 ± 24.0 vs 66.5 ± 22.6, p=0.11). The ACRODAT® overall status decreased from 84.3 ± 27.6 to 33.8 ± 17.1 (p=0.001) and there was a decline in the summation of the tumor status, comorbidities, symptoms and health-related qualify of life impairment score (7.1 ± 1.8 vs 6.4 ± 1.8, p=0.02). Hemoglobin A1c, fasting lipids, liver enzymes and renal function were not significantly affected. Repeat MRI of the sella at 6 months showed no change. Conclusions: In spite of the small number of patients participating in this study, strict control in patients with a modest IGF-1 elevation was accompanied by clinical improvements detected by the PASQ and ACRODAT®. Our results support the notion that strict IGF-1 control can be accompanied by improvement in clinical symptoms with lower PASQ scores. These findings need to be confirmed in a larger scale clinical trial. Presentation: 6/2/2024