Sleep and Breathing Conference highlights 2023: a summary by ERS Assembly 4.

This paper presents some of the highlights of the Sleep and Breathing Conference 2023 https://bit.ly/46MxJml.

Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant.

INTRODUCTION: Disorders of glucose metabolism are a serious acromegaly comorbidity and may be differently impacted by medical treatments of acromegaly. In this retrospective longitudinal multicenter study, we investigated the outcome of glucose metabolism and its predictors in patients treated with Pasireotide LAR (PAS-LAR) alone or in combination with Pegvisomant (PAS-LAR + Peg-V). SUBJECTS AND METHODS: Acromegaly patients treated continously with PAS-LAR or PAS-LAR + Peg-V for at least 6 months. RESULTS: Forty patients (25 females, 15 males) were enrolled. At last visit, 27/40 patients (67.5%) reached biochemical control of acromegaly. Overall, glucose metabolism improved in 3 (all in PAS-LAR + Peg-V; 7.5%), worsened in 26 (65%) and remained unchanged in 11 patients (27.5%). Glucose metabolism worsened in 25 patients (73.5%) treated with PAS-LAR and in a single patient (16.7%) treated with PAS-LAR + Peg-V (p < 0.001). Among patients treated with Pas-LAR alone, GH at baseline was higher in those with worsening of glucose metabolism (p = 0.04) as compared to those with stable glucose status. A significantly higher reduction of HbA1c was observed in patients treated with PAS-LAR + Peg-V, as compared with those treated with PAS-LAR alone (p = 0.005). CONCLUSIONS: Our data confirmed that glucose metabolism in patients treated with PAS-LAR is often worsened, and may be predicted by entity of baseline GH hypersecretion and by the dose of PAS-LAR. Moreover, our data, although limited by small numbers, may suggest that the combination treatment PAS-LAR + Peg-V can improve glucose homeostasis in selected patients.

Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response.

BACKGROUND: The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. METHODS: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. RESULTS: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2-4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4-4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1-6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4-3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4-8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3-6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3-20.0). CONCLUSION: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

Effects of Pegvisomant and Pasireotide LAR on Vertebral Fractures in Acromegaly Resistant to First-generation SRLs.

PURPOSE: Osteopathy is an emerging complication of acromegaly. In somatostatin receptor ligands (SRL)-resistant patients, pegvisomant (PegV) and pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined. METHODS: In a longitudinal retrospective international study, we evaluated incidence of radiological vertebral fractures (VFs) in 55 patients with acromegaly resistant to first-generation SRL. RESULTS: At study entry, prevalent VFs occurred in 23 patients (41.8%). Biochemical acromegaly control was reached in 66.7% of patients on PegV and in 66.7% of patients on Pasi. During the follow-up, incident VFs (iVFs) were detected in 16 patients (29.1%). Occurrence of iVFs was associated with prevalent VFs (P = .002), persistence of active acromegaly (P = .01) and higher value of insulin-like growth factor 1 (IGF-1) during follow-up (P = .03). Among patients with active disease at last visit, iVFs occurred less frequently in patients on treatment with Pasi (25%) compared to PegV (77.8% P = .04), independently of the IGF-1 values (P = .90). In patients who reached biochemical control, 22.7% on PegV and 12.5% on Pasi had iVFs (P = .40). Among both treatment groups, the presence of pre-existent VFs was the main determinant for iVFs. CONCLUSION: Our data show for the first time that patients with biochemically active disease treated with Pasi had lower risk of iVFs versus those treated with PegV. It also confirms that the presence of pre-existent VFs was the main determinant for iVFs. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings.