8008 Insulin-like Growth Factor-1 (IGF-1) Level Fluctuations and Patient Reported Outcomes (PROMS) During Treatment with Long-acting Somatostatin Receptor Ligands (SRLs) for Acromegaly: a Prospective Study
Authors: Remba-Shapiro Ilan , Schweizer Júnia R O L , Liebert Karen J P , Schilbach Katharina , Adams Michelle , Tritos Nicholas A , Bidlingmaier Martin , Nachtigall Lisa B 
Published: October 2024

Disclosure: I. Remba-Shapiro: None. J.R. Schweizer: None. K.J. Liebert: Consulting Fee; Self; Crinetics, Recordati Rare Diseases, Novo Nordisk. K. Schilbach: None. M. Adams: Consulting Fee; Self; Chiesi. N.A. Tritos: None. M. Bidlingmaier: Consulting Fee; Self; Ipsen, Ionis Pharmaceuticals Inc., Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Inc., Roche Pharmaceuticals. L.B. Nachtigall: Consulting Fee; Self; Crinetics. Grant Recipient; Self; Amryt, Recordati Rare Diseases.

Background: SRLs are the most used medical therapy for acromegaly. Some patients report symptoms of acromegaly towards the end of the injection cycle even when IGF-1 levels are controlled. IGF-1 fluctuations within an injection cycle have been observed. In this study we investigated the variability of biochemical markers and PROMS in patients receiving long-acting SRLs. Methods: Subjects with acromegaly controlled with monthly lanreotide depot or octreotide LAR were recruited. Blood samples at 1 and 4 weeks after SLR injection were collected in 2 consecutive cycles. Clinical characteristics were evaluated. Quality of life (QoL) surveys included: Acromegaly Quality of Life Questionnaire (AcroQoL) (higher scores = better QoL) and Patient Assessed Acromegaly Symptom Questionnaire (PASQ) (higher scores = worse QoL). Week 1 vs. week 4 values were compared. Quest Diagnostics LC-MS assay was used to measure IGF-1. Coefficient of variation (CV = (IGF-1 SD)/(IGF-1 mean)%) of IGF-1 was calculated. Values ≤5% were interpreted as being a consequence of assay variability. Variables are presented as mean (SD) and compared using t-test; p &lt;0.05 was considered significant. Results: Patients (6 women, 4 men) had a mean age of 56.1 (15.4) years. Eight underwent TSS. One had diabetes mellitus, 3 had hypertension. Mean IGF-1 index (IGF-1 x upper limit of normal) at screening was 0.63 (0.23). BMI was 27.7 (5.8) kg/m2. IGF-1 index at week 1 was 0.57 [0.16] vs. 0.61 [0.23] at week 4, p=0.271. Insulin levels were lower in week 1 vs. week 4 (7.3 [4.4] vs. 9.7 [6.0]mIU/mL p=0.041). There were no significant differences in GH, glucose, weight, blood pressure and ring size in week 1 vs. week 4. PASQ varied significantly within the injection cycle with higher scores in week 4 (18.1 [10.8]) compared to week 2 (16.1 [10.4] p=0.032) and week 3 (14.2 [8.8] p= 0.002). ACROQoL scores did not differ by injection phase. IGF-1 increased more than assay CV from week 1 to week 4 in 8/20 (40%) determinations. An ROC curve identified an IGF-1 index cutoff of 0.57 at week 4 (AUC: 0.812, p=0.021) as a predictor of IGF-1 index increase within the injection cycle (CV &gt; 5%): sensitivity 88%, specificity 75%. Five patients had IGF-1 index &gt; 0.57 at week 4 during both cycles (range 0.60-1.2). In this group, mean IGF-1 index was higher at week 4 vs. week 1 (0.77 [0.21] vs. 0.66 [0.14] p=0.026). The 5 patients with IGF-1 index &lt; 0.57 at week 4 had no difference in IGF-1 index between week 4 and week 1 (0.48 [0.14] vs. 0.44 [0.09] p=0.144). Conclusions: This prospective study of patients with acromegaly controlled with long-acting SRLs demonstrates injection phase variability in self-reported symptoms by PASQ. An IGF-1 index &gt; 0.57 at the end of the cycle may warrant injection phase-dependent monitoring. Larger studies to confirm the IGF-1 cutoff above which patients should be monitored in a cycle-dependent manner will allow an individualized approach to optimize management.

Presentation: 6/2/2024