Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Characteristics and outcome of patients with low-/intermediate-risk acute promyelocytic leukemia treated with arsenic trioxide - an international collaborative study

The aim of this study was to characterize a large series of 154 patients with acute promyelocytic leukemia (APL; median age, 53 years; range, 18-90 years) and evaluate real-life outcome after up-front treatment with arsenic trioxide (ATO) and alltrans retinoic acid (ATRA). All patients were included in the prospective NAPOLEON registry (NCT02192619) between 2013 and 2019. APL was de novo in 91% (n=140) and therapy-related in 9% (n=14); 13% (n=20) were older than 70 years. At diagnosis bleeding/hemorrhage was present in 38% and thrombosis in 3%. Complete remission was achieved in 152 patients (99%), whereas two patients (1%) experienced induction death within 18 days after start of therapy. With a median follow-up of 1.99 years (95%-CI, 1.61-2.30 years) 1-year and 2-years overall survival (OS) rates were 97% (95%-CI, 94-100%) and 95% (95%-CI, 91-99%), respectively. Age above 70 years was associated with a significantly shorter OS (P<0.001) as compared to younger patients. So far no relapses were observed. Six patients (4%) died in CR after in median 0.95 years after diagnosis (range, 0.18-2.38 years). Our data confirm the efficiency and durability of ATO/ATRA in the primary management of adult low-/ intermediate-risk APL patients in the real life setting, irrespective of age