METHODOLOGY: All sera for AT1R-Ab were collected at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The sera were centrifuged and kept refrigerated at -80 °C before being transported to the South Australian Transplantation and Immunogenetics Laboratory (SATIS). Enzyme-linked immunosorbent assay kit (One Lambda) was used for the detection of AT1R-Ab, and it was performed according to the manufacturer's instructions. The level of >17.1 U/mL was considered to be AT1R-Ab positive; 10.0-17.1 U/mL at risk, and <10.0 U/mL negative.

RESULTS: A total of 115 samples were collected from 99 patients pre and post-kidney transplant recipients. From the pre-transplant sera (n = 68) 17.7% were positive, 35.3% were at risk and 47.0% were negative. The positive AT1R-Ab cohort were relatively younger, with a mean age of 34.7 ± 8.3 years old and statistically significant, with a p-value of 0.028. Among the sera that were tested positive, 19.0% were from the Chinese ethnicity, 6.7% from Malay and 16.7% from Indian. There was no difference in the rejection episodes, persistent or de novo HLA-DSA, and graft function between the group (AT1R-Ab negative vs AT1R-Ab at risk and positive) and the results were consistent in a model adjusted for all potential confounders.

METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies.

RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo.