Hydroxychloroquine in the primary thrombosis prophylaxis of antiphospholipid antibody positive patients without systemic autoimmune disease.

Objective The objective of this study was to determine the efficacy of hydroxychloroquine (HCQ) in the primary thrombosis prevention of antiphospholipid antibody (aPL)-positive patients with no other systemic autoimmune diseases. Methods Under the auspices of Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking, a multicenter, international, randomized controlled trial (RCT) was initiated, in which persistently aPL-positive but thrombosis-free patients without systemic autoimmune diseases were randomized to receive HCQ or no treatment in addition to their standard regimen. The primary objective was the efficacy of HCQ in preventing the first thrombosis. The secondary objectives were the thrombosis incidence rate, and the effects of HCQ on aPL profile and mortality rate. Patients were risk-stratified based on antiplatelet agent use. The goal was to follow patients every 6 months for 5 years. Results We recruited 20 persistently aPL-positive patients (female: 19, mean age: 46.6 ± 9.9 years, and baseline antiplatelet medication: 14); 9/20 were randomized to HCQ. During the mean follow-up of 1.7 years, no patients developed thrombosis or a serious adverse event. The study was terminated early due to the low recruitment rate, exacerbated by the prolonged manufacturing shortage and significant price increase of HCQ in the United States. Conclusion Given that a small number of patients with a relatively short follow-up were enrolled in our RCT, and no patients developed thrombosis, we cannot accurately assess the effectiveness of HCQ for primary thrombosis prevention in persistently aPL-positive patients with no other systemic autoimmune diseases. Our experience suggests that conducting an international RCT, especially without pharmaceutical support, is an extremely challenging undertaking.

Polymorphisms in the IL28B gene (rs12979860, rs8099917) and the virological response to pegylated interferon therapy in hepatitis D virus patients.

AIM: Few data are available regarding the effects of interleukin 28B (IL28B) polymorphisms in chronic hepatitis D (CHD) patients. This study investigated the relationship between IL28B poly-morphisms and the response of patients with CHD infections to pegylated interferon (PEG-IFN) therapy. MATERIALS AND METHODS: A total of 101 CHD patients were -selected, 80 of whom (46 males ; median age 41 years) satisfied the inclusion criteria and were enrolled in the study. Thirty-seven patients were treated with peg-IFNα for at least 12 months and were followed for a median of 18 months (range, 12-30 months). The primary treatment endpoint was the suppression of HDV replication, as documented by the loss of detectable HDV RNA in serum. Genotyping was used to analyse the IL28B polymorphisms rs12979860 and rs8099917 according to the virological response. RESULTS: After treatment, a sustained viral response (SVR) was achieved in 19 (51%) of the patients treated with PEG-INF. The IL28B genotypes in the 80 patients were as follows : CC in 36 (45%), CT in 33 (41%) and TT in 11 (14%) for rs12979860, and GG in 4 (5%), GT in 27 (34%) and TT in 49 (61%) for rs8099917. SVR was achieved in 5 (26%), 10 (53%) and 4 (21%) patients with CC, CT and TT at rs12979860, respectively, and one (5%), nine (47%) and nine (47%) patients with GG, GT and TT at rs8099917, respectively. There were differences in the SVR among genotypes (rs12979860 and rs8099917 ; chi-squared test, p = 0.047). CONCLUSION: IL28B predicts the PEG-IFN response in patients with CHD infection.