Alpha-1 Antitrypsin Deficiency-Associated Clinical Manifestations and Healthcare Resource Use in the United States.

Pulmonary events (PEs) associated with alpha-1 antitrypsin deficiency (AATD) can have a severe clinical course and increase healthcare resource use (HRU). However, AATD-associated HRU and healthcare costs have not been extensively described. This study describes and compares real-world HRU and healthcare costs among US patients with severe (requiring hospitalization after AATD-related PE) versus nonsevere AATD clinical course. Administrative healthcare claims for patients with a second primary AATD diagnosis between 6/1/2008 and 12/31/2017 were analyzed from 2 databases (requiring continuous enrollment 6 months preceding diagnosis). Patient baseline characteristics and AATD-associated PE incidence rates, HRU, and healthcare costs during follow-up were compared in patients with severe versus nonsevere AATD. Of 5109 patients with a second AATD diagnosis, 2674 (severe, n = 711 [26.6%]; nonsevere, n = 1963 [73.4%]) had ≥1 AATD-associated PE. PE incidence per 100 person-years was higher in patients with severe versus nonsevere AATD. Annual incidences (mean ± SD) of emergency department (1.2 ± 5.7 vs. 0.4 ± 1.2), inpatient (1.3 ± 2.5 vs. 0.1 ± 0.5), and outpatient (10.3 ± 15.9 vs. 5.7 ± 13.2) visits were higher in patients with severe versus nonsevere AATD. Median (interquartile range) annual costs were also higher for patients with severe versus nonsevere AATD for emergency department ($185 [$0-$1665] vs. $0 [$0-$264]), inpatient ($16,038 [$2968-$70,941] vs. $0 [$0-$0]), and outpatient ($2663 [$412-$10,277] vs. $1114 [$134-$4195]) visits. Higher percentages of patients with severe AATD were prescribed augmentation therapy, antibiotics, or corticosteroids. These findings suggest that patients with severe AATD have higher incidence of AATD-associated PEs, as well as higher HRU and healthcare costs.

Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.

The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.

Sildenafil citrate does not reduce exercise tolerance in men with erectile dysfunction and chronic stable angina.

AIMS: The aim of this study was to evaluate whether sildenafil, used for treatment of erectile dysfunction (ED), affects the exercise tolerance and ischaemic threshold in men with exercise-induced angina not taking nitrates. METHODS: This was a double-blind placebo-controlled study in men with ED and chronic stable angina, assessing the effect of sildenafil on time to limiting angina during incremental treadmill exercise. Patients remained on their antianginal therapy and received a 100-mg dose of sildenafil or placebo 1h prior to treadmill exercise. Other measurements included times to onset of angina, 1-mm ST-segment depression, and total exercise time. RESULTS: Adjusted treatment differences for the time to limiting angina, time to onset of angina, total exercise time, and time to 1-mm ST-segment depression were (mean+/-SE) 20+/-10s (95% CI, 1-39; P=0.040), 32+/-11s (95% CI, 11-53; P=0.004), 20+/-10s (95% CI, 0-39; P=0.049), and 12+/-17s (95% CI, -21 to 45, P=0.48), respectively, in favour of sildenafil. There were no serious treatment-related adverse events. CONCLUSIONS: Sildenafil was well tolerated and did not adversely affect any exercise parameter in men with coronary artery disease and ED. Favourable trends in total exercise duration and times to onset of angina and limiting angina were recorded with sildenafil use.