A Study To Evaluate Both The Efficacy and Safety Profile of CP-690,550 In Patients With Moderately to Severely Active Ulcerative Colitis

Summary

This study is designed to evaluate the efficacy and safety of tofacitinib (CP-690,550) in patients with moderate to severe ulcerative colitis who have failed or be intolerant to one of following treatments for ulcerative colitis: oral steroids, azathiopurine/6-mercaptopurine, or anti-TNF-alpha therapy.

Timeline

Start

2012-06

Primary completion

2015-05

Completion

2015-06

Outcome

Met primary endpoint

registry NUMBER Tofacitinib 10 mg BID: 16.6 percentage of participants NCT01458951 ↗

registry analysis (superiority or other test); Tofacitinib 10 mg BID vs Placebo BID; p = 0.0005; Percentage difference 13.0 (95% CI 8.1 to 17.9); CMH Chi-square Test NCT01458951 ↗

Publications

• Panes J, D'Haens GR, Sands BE, Ng SC, Lawendy N, Kulisek N, Guo X, Wu J, Vranic I, Panaccione R, Vermeire S. Analysis of tofacitinib safety in ulcerative colitis from the completed global clinical developmental program up to 9.2 years of drug exposure. United European Gastroenterol J. 2024 Jul;12(6):793-801. doi: 10.1002/ueg2.12584. Epub 2024 May 22.
• Rubin DT, Torres J, Regueiro M, Reinisch W, Prideaux L, Kotze PG, Tan FH, Gardiner S, Mundayat R, Cadatal MJ, Ng SC. Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis. Crohns Colitis 360. 2024 Jan 20;6(1):otae004. doi: 10.1093/crocol/otae004. eCollection 2024 Jan.
• Rubin DT, Salese L, Cohen M, Kotze PG, Woolcott JC, Su C, Mundayat R, Paulissen J, Torres J, Long MD. Presence of risk factors associated with colectomy among patients with ulcerative colitis: a post hoc analysis of data from the tofacitinib OCTAVE ulcerative colitis clinical program. Ther Adv Gastroenterol. 2023 Aug 7;16:17562848231189122. doi: 10.1177/17562848231189122. eCollection 2023.
• Schreiber S, Rubin DT, Ng SC, Peyrin-Biroulet L, Danese S, Modesto I, Guo X, Su C, Kwok KK, Jo H, Chen Y, Yndestad A, Reinisch W, Dubinsky MC. Major Adverse Cardiovascular Events by Baseline Cardiovascular Risk in Patients with Ulcerative Colitis Treated with Tofacitinib: Data from the OCTAVE Clinical Programme. J Crohns Colitis. 2023 Nov 24;17(11):1761-1770. doi: 10.1093/ecco-jcc/jjad104.
• Kristensen LE, Danese S, Yndestad A, Wang C, Nagy E, Modesto I, Rivas J, Benda B. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL Surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.
• Lichtenstein GR, Cohen BL, Salese L, Modesto I, Wang W, Chan G, Ahmed HM, Su C, Peyrin-Biroulet L. Impact of Concomitant Corticosteroids on Tofacitinib Induction Efficacy and Infection Rates in Ulcerative Colitis. Dig Dis Sci. 2023 Jun;68(6):2624-2634. doi: 10.1007/s10620-022-07794-0. Epub 2023 Feb 4.
• Dubinsky MC, Armuzzi A, Gecse KB, Ullman T, Bushmakin AG, DiBonaventura M, Cappelleri JC, Connelly SB, Woolcott JC, Salese L. Improvements in Disease Activity Partially Mediate the Effect of Tofacitinib Treatment on Generic and Disease-Specific Health-Related Quality of Life in Patients with Ulcerative Colitis: Data from the OCTAVE Program. Dig Dis. 2023;41(4):604-614. doi: 10.1159/000528788. Epub 2023 Jan 5.
• Winthrop KL, Yndestad A, Henrohn D, Danese S, Marsal S, Galindo M, Woolcott JC, Jo H, Kwok K, Shapiro AB, Jones TV, Diehl A, Su C, Panes J, Cohen SB. Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs. Rheumatol Ther. 2023 Apr;10(2):357-373. doi: 10.1007/s40744-022-00507-z. Epub 2022 Dec 17.
• Sandborn WJ, Sands BE, Vermeire S, Leung Y, Guo X, Modesto I, Su C, Wang W, Panes J. Modified Mayo score versus Mayo score for evaluation of treatment efficacy in patients with ulcerative colitis: data from the tofacitinib OCTAVE program. Ther Adv Gastroenterol. 2022 Dec 5;15:17562848221136331. doi: 10.1177/17562848221136331. eCollection 2022.
• Lichtenstein GR, Bressler B, Francisconi C, Vermeire S, Lawendy N, Salese L, Sawyerr G, Shi H, Su C, Judd DT, Jones T, Loftus EV. Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program. Inflamm Bowel Dis. 2023 Jan 5;29(1):27-41. doi: 10.1093/ibd/izac084.
• Hudesman DP, Torres J, Salese L, Woolcott JC, Mundayat R, Su C, Mosli MH, Allegretti JR. Long-Term Improvement in the Patient-Reported Outcomes of Rectal Bleeding, Stool Frequency, and Health-Related Quality of Life with Tofacitinib in the Ulcerative Colitis OCTAVE Clinical Program. Patient. 2023 Mar;16(2):95-103. doi: 10.1007/s40271-022-00603-w. Epub 2022 Nov 7.
• Targownik L, Dubinsky MC, Steinwurz F, Bushmakin AG, Cappelleri JC, Tai E, Gardiner S, Hur P, Panes J. Disease Activity and Health-related Quality of Life Relationships with Work Productivity in Patients with Ulcerative Colitis in OCTAVE Induction 1 and 2 and OCTAVE Sustain. J Crohns Colitis. 2023 Apr 19;17(4):513-523. doi: 10.1093/ecco-jcc/jjac161.
• Sandborn WJ, D'Haens GR, Sands BE, Panaccione R, Ng SC, Lawendy N, Kulisek N, Modesto I, Guo X, Mundayat R, Su C, Vranic I, Panes J. Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up to 7.8 Years of Safety Data from the Global Clinical Programme. J Crohns Colitis. 2023 Apr 3;17(3):338-351. doi: 10.1093/ecco-jcc/jjac141.
• Loftus EV, Baumgart DC, Gecse K, Kinnucan JA, Connelly SB, Salese L, Su C, Kwok KK, Woolcott JC, Armuzzi A. Clostridium difficile Infection in Patients with Ulcerative Colitis Treated with Tofacitinib in the Ulcerative Colitis Program. Inflamm Bowel Dis. 2023 May 2;29(5):744-751. doi: 10.1093/ibd/izac139.
• Winthrop KL, Vermeire S, Long MD, Panes J, Ng SC, Kulisek N, Mundayat R, Lawendy N, Vranic I, Modesto I, Su C, Melmed GY. Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflamm Bowel Dis. 2023 Jan 5;29(1):85-96. doi: 10.1093/ibd/izac063.
• Mukherjee A, Tsuchiwata S, Nicholas T, Cook JA, Modesto I, Su C, D'Haens GR, Sandborn WJ. Exposure-Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results From Phase II and Phase III Induction and Maintenance Studies. Clin Pharmacol Ther. 2022 Jul;112(1):90-100. doi: 10.1002/cpt.2601. Epub 2022 Apr 27.
• Dubinsky MC, Magro F, Steinwurz F, Hudesman DP, Kinnucan JA, Ungaro RC, Neurath MF, Kulisek N, Paulissen J, Su C, Ponce de Leon D, Regueiro M. Association of C-reactive Protein and Partial Mayo Score With Response to Tofacitinib Induction Therapy: Results From the Ulcerative Colitis Clinical Program. Inflamm Bowel Dis. 2023 Jan 5;29(1):51-61. doi: 10.1093/ibd/izac061.
• Feagan BG, Khanna R, Sandborn WJ, Vermeire S, Reinisch W, Su C, Salese L, Fan H, Paulissen J, Woodworth DA, Niezychowski W, Sands BE. Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: results from the tofacitinib OCTAVE trials. Aliment Pharmacol Ther. 2021 Dec;54(11-12):1442-1453. doi: 10.1111/apt.16626. Epub 2021 Oct 6.
• Farraye FA, Qazi T, Kotze PG, Moore GT, Mundayat R, Lawendy N, Sharma PP, Judd DT. The impact of body mass index on efficacy and safety in the tofacitinib OCTAVE ulcerative colitis clinical programme. Aliment Pharmacol Ther. 2021 Aug;54(4):429-440. doi: 10.1111/apt.16439. Epub 2021 Jun 24.
• Rubin DT, Reinisch W, Greuter T, Kotze PG, Pinheiro M, Mundayat R, Maller E, Fellmann M, Lawendy N, Modesto I, Vavricka SR, Lichtenstein GR. Extraintestinal manifestations at baseline, and the effect of tofacitinib, in patients with moderate to severe ulcerative colitis. Ther Adv Gastroenterol. 2021 May 16;14:17562848211005708. doi: 10.1177/17562848211005708. eCollection 2021.
• Sandborn WJ, Peyrin-Biroulet L, Sharara AI, Su C, Modesto I, Mundayat R, Gunay LM, Salese L, Sands BE. Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status. Clin Gastroenterol Hepatol. 2022 Mar;20(3):591-601.e8. doi: 10.1016/j.cgh.2021.02.043. Epub 2021 Mar 6.
• Vong C, Martin SW, Deng C, Xie R, Ito K, Su C, Sandborn WJ, Mukherjee A. Population Pharmacokinetics of Tofacitinib in Patients With Moderate to Severe Ulcerative Colitis. Clin Pharmacol Drug Dev. 2021 Mar;10(3):229-240. doi: 10.1002/cpdd.899. Epub 2021 Jan 29.
• Curtis JR, Regueiro M, Yun H, Su C, DiBonaventura M, Lawendy N, Nduaka CI, Koram N, Cappelleri JC, Chan G, Modesto I, Lichtenstein GR. Tofacitinib Treatment Safety in Moderate to Severe Ulcerative Colitis: Comparison of Observational Population Cohort Data From the IBM MarketScan(R) Administrative Claims Database With Tofacitinib Trial Data. Inflamm Bowel Dis. 2021 Aug 19;27(9):1394-1408. doi: 10.1093/ibd/izaa289.
• Sandborn WJ, Peyrin-Biroulet L, Quirk D, Wang W, Nduaka CI, Mukherjee A, Su C, Sands BE. Efficacy and Safety of Extended Induction With Tofacitinib for the Treatment of Ulcerative Colitis. Clin Gastroenterol Hepatol. 2022 Aug;20(8):1821-1830.e3. doi: 10.1016/j.cgh.2020.10.038. Epub 2020 Oct 27.
• Sands BE, Colombel JF, Ha C, Farnier M, Armuzzi A, Quirk D, Friedman GS, Kwok K, Salese L, Su C, Taub PR. Lipid Profiles in Patients With Ulcerative Colitis Receiving Tofacitinib-Implications for Cardiovascular Risk and Patient Management. Inflamm Bowel Dis. 2021 May 17;27(6):797-808. doi: 10.1093/ibd/izaa227.
• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.
• Dubinsky MC, DiBonaventura M, Fan H, Bushmakin AG, Cappelleri JC, Maller E, Thorpe AJ, Salese L, Panes J. Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies. Inflamm Bowel Dis. 2021 Jun 15;27(7):983-993. doi: 10.1093/ibd/izaa193.
• Lichtenstein GR, Rogler G, Ciorba MA, Su C, Chan G, Pedersen RD, Lawendy N, Quirk D, Nduaka CI, Thorpe AJ, Panes J. Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across the Ulcerative Colitis Clinical Program. Inflamm Bowel Dis. 2021 May 17;27(6):816-825. doi: 10.1093/ibd/izaa199.
• Sandborn WJ, Panes J, Sands BE, Reinisch W, Su C, Lawendy N, Koram N, Fan H, Jones TV, Modesto I, Quirk D, Danese S. Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme. Aliment Pharmacol Ther. 2019 Nov;50(10):1068-1076. doi: 10.1111/apt.15514. Epub 2019 Oct 9.
• Sands BE, Taub PR, Armuzzi A, Friedman GS, Moscariello M, Lawendy N, Pedersen RD, Chan G, Nduaka CI, Quirk D, Salese L, Su C, Feagan BG. Tofacitinib Treatment Is Associated With Modest and Reversible Increases in Serum Lipids in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2020 Jan;18(1):123-132.e3. doi: 10.1016/j.cgh.2019.04.059. Epub 2019 May 8.
• Sandborn WJ, Panes J, D'Haens GR, Sands BE, Su C, Moscariello M, Jones T, Pedersen R, Friedman GS, Lawendy N, Chan G. Safety of Tofacitinib for Treatment of Ulcerative Colitis, Based on 4.4 Years of Data From Global Clinical Trials. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1541-1550. doi: 10.1016/j.cgh.2018.11.035. Epub 2018 Nov 23.
• Hanauer S, Panaccione R, Danese S, Cheifetz A, Reinisch W, Higgins PDR, Woodworth DA, Zhang H, Friedman GS, Lawendy N, Quirk D, Nduaka CI, Su C. Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019 Jan;17(1):139-147. doi: 10.1016/j.cgh.2018.07.009. Epub 2018 Sep 10.
• Winthrop KL, Melmed GY, Vermeire S, Long MD, Chan G, Pedersen RD, Lawendy N, Thorpe AJ, Nduaka CI, Su C. Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. Inflamm Bowel Dis. 2018 Sep 15;24(10):2258-2265. doi: 10.1093/ibd/izy131.
• Motoya S, Watanabe M, Kim HJ, Kim YH, Han DS, Yuasa H, Tabira J, Isogawa N, Arai S, Kawaguchi I, Hibi T. Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies. Intest Res. 2018 Apr;16(2):233-245. doi: 10.5217/ir.2018.16.2.233. Epub 2018 Apr 30.
• Panes J, Vermeire S, Lindsay JO, Sands BE, Su C, Friedman G, Zhang H, Yarlas A, Bayliss M, Maher S, Cappelleri JC, Bushmakin AG, Rubin DT. Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies. J Crohns Colitis. 2018 Jan 24;12(2):145-156. doi: 10.1093/ecco-jcc/jjx133.
• Sandborn WJ, Su C, Sands BE, D'Haens GR, Vermeire S, Schreiber S, Danese S, Feagan BG, Reinisch W, Niezychowski W, Friedman G, Lawendy N, Yu D, Woodworth D, Mukherjee A, Zhang H, Healey P, Panes J; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017 May 4;376(18):1723-1736. doi: 10.1056/NEJMoa1606910.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Tofacitinib	Small molecule	10 mg	Oral

Indications