Objective: To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40-120 mg/week) in acromegaly. Design: This is a 28-week, multicenter, open-label, single-arm sequential study. Methods: Patients (nZ92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (nZ57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40-80 mg once weekly or 40 or 60 mg twice weekly). Results: In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P!0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P!0.0001) with median pegvisomant dose at 60 mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (K0.6G1.6) and soft tissue swelling (K0.6G1.8).Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related -thrombocytopenia, urticaria; not treatment related -abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to O5!upper limit of normal with normalization after withdrawal). Conclusions: In patients partially controlled by SSAs, LA (120 mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.

A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA.

The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure.

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Protein kinase C (PKC) activity and expression were measured in 54 adenomas (prolactin (PRL)-, growth hormone (GH)- and non-secreting), 1 of them obtained from a patient treated with the dopamine agonist bromocriptine and 2 from patients treated with the somatostatin analog octreotide. They were also measured in normal human and rat pituitaries. Total PKC activity was measured by incorporation of 32P into histones, and PKC expression by dot blot immunoquantification using purified PKC as a standard. Both enzyme activity and expression were higher in adenomatous pituitaries than in normal human or rat pituitaries. PKC expression in GH-secreting and non-secreting tumors was significantly higher than that in PRL-secreting tumors. Furthermore, it was significantly higher invasive tumors than in non-invasive tumors. In the 3 adenomas which were obtained from patients treated with bromocriptine or octreotide and which were used for PKC-activity measurement, particulate- and soluble-PKC activities were significantly lower than those measured in non-treated adenomas.