Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. DESIGN: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. CONCLUSIONS: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects.

Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies.

Neonatal alloimmune thrombocytopenic purpura induced by anti-Bak(a): a case report and review of the literature.

We report a case of neonatal alloimmune thrombocytopenic purpura after an uneventful pregnancy. The baby had systemic purpura at birth and his platelet count was 6 X 10(9)/1. He was treated with maternal platelets and one week later his platelets were normalized. It was the second pregnancy of the mother; she received a blood transfusion after the delivery of her first child. The mother was HLA DR3 positive, an antigen frequently implicated in neonatal alloimmune thrombocytopenic purpura. The antibody reacted with both P1A1 positive and negative platelets which excluded anti-P1A1 type, the antibody most involved in neonatal alloimmune thrombocytopenia. This antibody reacted with platelets of 46 out of 53 random donors (87%); this approached the 90.8% frequency of Bak(a) reported in the Netherlands. Later this antibody was typed as anti-Bak(a). A discussion and a review of the literature is given.