Treatment Patterns, Adherence, Persistence, and Health Care Resource Utilization in Acromegaly: A Real-World Analysis.

Context: Treatment of acromegaly is multimodal for many patients, and medical treatments include somatostatin receptor ligands (SRLs), dopamine agonists (DAs), and growth hormone receptor antagonists (GHRAs). However, recent real-world evidence on treatment patterns for patients with acromegaly is limited. Objective: This study evaluated medication usage, treatment changes, adherence, persistence, comorbidities, and health care resource utilization using deidentified data from MarketScan, a US claims database. Methods: Eligible patients (n = 882) were those receiving monotherapy or combination therapy for ≥90 days without treatment gaps. Results: Mean age at diagnosis was 48.6 years; 50.1% of patients were female. Over half (59.4%) had 1 line of treatment (LOT); 23.1% had 2 LOTs; 17.5% had at least 3 LOTs. Most patients (94.6%) initiated treatment with monotherapies. The most common first-line monotherapy treatments were cabergoline (DA, 36.8%), octreotide long-acting release (first-generation SRL, 29.5%), and lanreotide depot (first-generation SRL, 22.5%). Adherence for first-line treatments (proportion of days covered) was higher for first-generation SRLs (lanreotide depot: 0.8) compared with DAs (0.7). Treatment persistence (time between the first treatment record and a change in LOT/censoring) in LOT 1 was higher for GHRAs (24.8 months) and first-generation SRLs (20.0 months) compared with DAs (14.4 months). Female patients and those diagnosed at a younger age were more likely to have shorter treatment persistence. The most prevalent comorbidities were hyperlipidemia, essential hypertension, and sleep apnea. Conclusion: Patients with more comorbidities had more health care visits during the first year after diagnosis, suggesting increased disease burden. Real-world evidence on treatment patterns provides insights into recommendations for individualized therapy.

Plasma protein biomarkers for the detection of pancreatic neuroendocrine tumors and differentiation from small intestinal neuroendocrine tumors.

There is an unmet need for novel biomarkers to diagnose and monitor patients with neuroendocrine neoplasms. The EXPLAIN study explores a multi-plasma protein and supervised machine learning strategy to improve the diagnosis of pancreatic neuroendocrine tumors (PanNET) and differentiate them from small intestinal neuroendocrine tumors (SI-NET). At time of diagnosis, blood samples were collected and analyzed from 39 patients with PanNET, 135 with SI-NET (World Health Organization Grade 1-2) and 144 controls. Exclusion criteria were other malignant diseases, chronic inflammatory diseases, reduced kidney or liver function. Prosed Oncology-II (i.e., OLink) was used to measure 92 cancer related plasma proteins. Chromogranin A was analyzed separately. Median age in all groups was 65-67 years and with a similar sex distribution (females: PanNET, 51%; SI-NET, 42%; controls, 42%). Tumor grade (G1/G2): PanNET, 39/61%; SI-NET, 46/54%. Patients with liver metastases: PanNET, 78%; SI-NET, 63%. The classification model of PanNET versus controls provided a sensitivity (SEN) of 0.84, specificity (SPE) 0.98, positive predictive value (PPV) of 0.92 and negative predictive value (NPV) of 0.95, and area under the receiver operating characteristic curve (AUROC) of 0.99; the model for the discrimination of PanNET versus SI-NET providing a SEN 0.61, SPE 0.96, PPV 0.83, NPV 0.90 and AUROC 0.98. These results suggest that a multi-plasma protein strategy can significantly improve diagnostic accuracy of PanNET and SI-NET.

Prevalence of comorbidities and concomitant medication use in acromegaly: analysis of real-world data from the United States.

PURPOSE: Patients receiving treatment for acromegaly often experience significant associated comorbidities for which they are prescribed additional medications. We aimed to determine the real-world prevalence of comorbidities and concomitant medications in patients with acromegaly, and to investigate the association between frequency of comorbidities and number of concomitantly prescribed medications. METHODS: Administrative claims data were obtained from the IBM® MarketScan® database for a cohort of patients with acromegaly, identified by relevant diagnosis codes and acromegaly treatments, and a matched control cohort of patients without acromegaly from January 2010 through April 2020. Comorbidities were identified based on relevant claims and assessed for both cohorts. RESULTS: Overall, 1175 patients with acromegaly and 5875 matched patients without acromegaly were included. Patients with acromegaly had significantly more comorbidities and were prescribed concomitant medications more so than patients without acromegaly. In the acromegaly and control cohorts, respectively, 67.6% and 48.4% of patients had cardiovascular disorders, the most prevalent comorbidities, and 89.0% and 68.3% were prescribed > 3 concomitant medications (p < 0.0001). Hypopituitarism and hypothalamic disorders, sleep apnea, malignant neoplasms and cancer, and arthritis and musculoskeletal disorders were also highly prevalent in the acromegaly cohort. A moderate, positive correlation (Spearman correlation coefficient 0.60) was found between number of comorbidities and number of concomitant medications in the acromegaly cohort. CONCLUSION: Compared with patients without acromegaly, patients with acromegaly have significantly more comorbidities and are prescribed significantly more concomitant medications. Physicians should consider the number and type of ongoing medications for individual patients before prescribing additional acromegaly treatments.

Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with acromegaly naïve to somatostatin-receptor ligands: analysis of three multicenter clinical trials.

PURPOSE: In clinical research involving acromegalic patients naïve to somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs octreotide LAR and pasireotide LAR, respectively, achieved GH < 2.5 ng/mL + normalized IGF-1 concentrations. The proportions achieving control appeared higher in the post-surgery compared with the de-novo setting with pasireotide, but more similar with octreotide. Using pooled data from multicenter clinical trials, we examined the biochemical efficacy of lanreotide depot/Autogel in similar settings. METHODS: Inclusion criteria: Ipsen-sponsored, 48-52-week trials in SRL-naïve acromegalic populations receiving lanreotide depot (60-120 mg); patients were included if de novo (no prior acromegaly treatment) or post-surgery (no medical treatment; radiotherapy allowed unless within previous 3 years). Efficacy endpoints included normalized IGF-1 levels and GH < 2.5 ng/mL + normalized IGF-1 at study end/last value available. ANALYSES: all patients (analysis #1) and subset with baseline GH > 5 ng/mL (analysis #2). RESULTS: Three studies were included. Analysis #1: normalized IGF-1 was achieved by 42% (71/171) of patients overall (post-surgery, 46% [21/46]; de-novo, 40% [50/125]); GH < 2.5 ng/mL + normalized IGF-1 was achieved by 35% (59/171) (39% [18/46] and 33% [41/125], respectively). Analysis #2: normalized IGF-1 levels, 39% (46/118) (post-surgery, 40% [10/25]; de-novo, 39% [36/93]); GH < 2.5 ng/mL + normalized IGF-1, 31% (36/118) (28% [7/25] and 31% [29/93], respectively). CONCLUSION: In these pooled analyses of SRL-naïve patients receiving lanreotide depot, 39-42% achieved IGF-1 control and 31-35% achieved GH and IGF-1 control. Control rates within post-surgery cohorts did not differ markedly from those in corresponding de-novo cohorts.