Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
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Clin. Gastroenterol. Hepatol. · Nov 2020
Multicenter StudyHepatic Disorders With the Use of Remdesivir for Coronavirus 2019.
Remdesivir is a nucleotide analog prodrug with antiviral activity against a broad spectrum of human coronavirus in cell cultures and mouse models including severe acute respiratory syndrome-associated coronavirus 2. Recently, the Food and Drug Agency (FDA) and the European Medicines Agency (EMA) recommended remdesivir for the treatment of patients hospitalized with severe coronavirus disease 2019 (COVID-19) infection.1,2 In the remdesivir clinical development program, some cases have raised concerns regarding potential hepatobiliary disorders associated with remdesivir, including in healthy volunteers and patients with COVID-19.3 In cohort studies of patients hospitalized for severe COVID-19 who were treated with compassionate-use remdesivir, elevated hepatic enzymes were the most frequent adverse drug reaction reported.4,5 In the first randomized, double-blind, placebo-controlled clinical trial assessing the effect of intravenous remdesivir in adults admitted to hospital with severe COVID-19 (n = 237), a higher proportion of remdesivir recipients than placebo recipients had dosing prematurely stopped by the investigators because of adverse events including aminotransferase or bilirubin increases (3 versus 0).6 Although there is no signal from the available data of severe hepatotoxicity or drug-induced liver injury in clinical trials, the number of patients exposed to remdesivir was too limited. Therefore, there is an urgent need to investigate the hepatic safety profile associated with remdesivir in COVID-19 patients.
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Clin. Gastroenterol. Hepatol. · Nov 2020
Systematic Review on Inflammatory Bowel Disease Patients With Coronavirus Disease 2019: It Is Time to Take Stock.
Data on the clinical characteristics of patients with inflammatory bowel diseases (IBDs) with coronavirus disease 2019 (COVID-19) are scarce. The aim of our systematic review was to investigate symptoms and diagnostic-therapeutic management of IBD patients with COVID-19. ⋯ Diarrhea occurs more frequently in IBD patients with COVID-19 than in the non-IBD population. Further studies are needed to define the optimal diagnostic-therapeutic approach in IBD patients with COVID-19.
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Clin. Gastroenterol. Hepatol. · Oct 2020
Efficacy and Safety of Extended Induction With Tofacitinib for the Treatment of Ulcerative Colitis.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment. ⋯ Overall, the majority of patients achieved a clinical response after 8 or 16 weeks' induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks' induction therapy. Most delayed responders at Month 36 were in remission. ClinicalTrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01470612.
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Clin. Gastroenterol. Hepatol. · Oct 2020
Maintenance of Remission With Tofacitinib Therapy in Patients With Ulcerative Colitis.
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib in patients with moderate to severe UC, up to 1 year, have been reported. We investigated maintenance of efficacy in patients in remission after 52 weeks of maintenance treatment in the pivotal phase 3 study (OCTAVE Sustain); these patients received open-label, long-term treatment with tofacitinib 5 mg twice daily. ⋯ Efficacy endpoints were maintained for up to 36 months, regardless of prior tofacitinib dose, including patients who reduced from tofacitinib 10 mg to 5 mg twice daily upon OCTAVE Open entry. No new safety risks were identified. ClinicalTrials.gov: OCTAVE Sustain (NCT01458574); OCTAVE Open (NCT01470612).