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INTRODUCTION: The objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks. METHODS: In this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study. Efficacy assessments included American College of Rheumatology (ACR) responses, Psoriasis Area Severity Index (PASI) responses, minimal disease activity (MDA), and 28-joint Disease Activity Score based on C-reactive protein (DAS28[CRP]). RESULTS: Of 185 randomized patients, 173 (93.5%) completed week 16 and 145 (78.4%) entered the open-label extension. Significantly more patients in each risankizumab arm achieved ACR20 at week 16 versus placebo (primary endpoint: pooled arms 1 + 2 [59.5%] versus placebo [35.7%]; treatment difference [90% CI] 24.0 [9.3, 38.7]; P = 0.007). Similarly, significantly more patients in most risankizumab arms achieved ACR20/50/70, PASI75/90/100, MDA, and greater improvements in DAS28(CRP) versus placebo at week 16. These benefits of risankizumab were maintained long term. Treatment-emergent adverse events were comparable across treatment arms. Risankizumab 150 mg was well tolerated over 76 weeks. CONCLUSIONS: Risankizumab improved joint and skin symptoms versus placebo in patients with active PsA over 16 weeks; improvements were sustained long term. Risankizumab was well tolerated over the long term with no new safety findings. TRIAL REGISTRATION NUMBERS: NCT02719171 and NCT02986373.
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INTRODUCTION: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups. METHODS: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy. Evidence of PHT included at least one of the following at baseline: FibroScan ≥ 20 kPa, platelets < 100 × 109/L, or medical history consistent with PHT. The primary efficacy endpoint was SVR12; adverse events (AEs) consistent with hepatic decompensation were assessed. RESULTS: PHT was identified in 60.6% (208/343) and 57.1% (224/392) of the 8- and 12-week groups, respectively. For those with PHT, SVR12 was 97.6% (203/208) and 98.7% (221/224) with 8- and 12-week treatment, respectively (intention-to-treat population). For those without PHT, 97.8% (132/135) in the 8-week group and 97.6% (164/168) in the 12-week group achieved SVR12. Eight patients with PHT, and seven without, did not achieve SVR12. Similar rates of AEs were observed in the PHT and non-PHT groups. Three cases of hepatic decompensation in the PHT group, unrelated to G/P according to the investigators, were reported. CONCLUSION: G/P treatment for 8 or 12 weeks was equally efficacious in HCV patients with features of PHT. Safety outcomes were similar between PHT and non-PHT groups, with G/P treatment well tolerated across groups. NCTS: NCT03089944, NCT02642432, NCT02738138, NCT02243293, NCT02651194, NCT03235349, NCT02707952, NCT02966795, NCT03069365, NCT03219216.
