Parakkal Deepak1, Quazim A Alayo2, Aava Khatiwada3, Bixuan Lin4, Marc Fenster5, Christina Dimopoulos6, Geoffrey Bader7, Roni Weisshof8, Michael Jacobs8, Alexandra Gutierrez3, Matthew A Ciorba3, George P Christophi9, Anish Patel7, Robert P Hirten6, Jean-Frederic Colombel6, David T Rubin8, Christina Ha10, Poonam Beniwal-Patel4, Ryan C Ungaro6, Gaurav Syal10, Joel Pekow8, Benjamin L Cohen11, Andres Yarur4. 1. Division of Gastroenterology and Inflammatory Bowel Diseases Center, Washington University in Saint Louis School of Medicine, St. Louis, Missouri. Electronic address: deepak.parakkal@wustl.edu. 2. Division of Gastroenterology and Inflammatory Bowel Diseases Center, Washington University in Saint Louis School of Medicine, St. Louis, Missouri; Division of Internal Medicine, St. Luke's Hospital, St. Louis, Missouri. 3. Division of Gastroenterology and Inflammatory Bowel Diseases Center, Washington University in Saint Louis School of Medicine, St. Louis, Missouri. 4. Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mt. Sinai, New York, New York; Division of Gastroenterology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York. 6. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mt. Sinai, New York, New York. 7. Division of Gastroenterology, Brooke Army Medical Center, Fort Sam Houston, Texas. 8. Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Department of Medicine, Chicago, Illinois. 9. Division of Gastroenterology and Inflammatory Bowel Diseases Center, Washington University in Saint Louis School of Medicine, St. Louis, Missouri; Steward Center for Inflammatory Bowel Diseases, Rockledge, Florida; University of Central Florida College of Medicine, Orlando, Florida. 10. Division of Digestive and Liver Diseases, Cedars Sinai Medical Center, Los Angeles, California. 11. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mt. Sinai, New York, New York; Department of Gastroenterology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio.
Abstract
BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.
BACKGROUND & AIMS: Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. METHODS: We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7-11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. RESULTS: AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4-30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9-11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). CONCLUSIONS: Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs.
Authors: Quazim A Alayo; Aava Khatiwada; Anish Patel; Maria Zulfiqar; Anas Gremida; Alexandra Gutierrez; Richard P Rood; Matthew A Ciorba; George Christophi; Parakkal Deepak Journal: Inflamm Bowel Dis Date: 2021-10-18 Impact factor: 7.290
Authors: Marc Fenster; Quazim A Alayo; Aava Khatiwada; Wenfei Wang; Christina Dimopoulos; Alexandra Gutierrez; Matthew A Ciorba; George P Christophi; Robert P Hirten; Christina Ha; Poonam Beniwal-Patel; Benjamin L Cohen; Gaurav Syal; Andres Yarur; Anish Patel; Jean-Frederic Colombel; Joel Pekow; Ryan C Ungaro; David T Rubin; Parakkal Deepak Journal: Clin Gastroenterol Hepatol Date: 2020-10-14 Impact factor: 13.576
Authors: Laura A Lucaciu; Nathan Constantine-Cooke; Nikolas Plevris; Spyros Siakavellas; Lauranne A A P Derikx; Gareth-Rhys Jones; Charles W Lees Journal: Therap Adv Gastroenterol Date: 2021-12-23 Impact factor: 4.409
Authors: Quazim A Alayo; Marc Fenster; Osama Altayar; Kerri L Glassner; Ernesto Llano; Kindra Clark-Snustad; Anish Patel; Lukasz Kwapisz; Andres J Yarur; Benjamin L Cohen; Matthew A Ciorba; Deborah Thomas; Scott D Lee; Edward V Loftus; David I Fudman; Bincy P Abraham; Jean-Frederic Colombel; Parakkal Deepak Journal: Crohns Colitis 360 Date: 2022-02-10
Authors: Idoia Busnadiego; Irene A Abela; Pascal M Frey; Daniel A Hofmaenner; Thomas C Scheier; Reto A Schuepbach; Philipp K Buehler; Silvio D Brugger; Benjamin G Hale Journal: PLoS Biol Date: 2022-07-05 Impact factor: 9.593