Profile of Tofacitinib in the Treatment of Ulcerative Colitis: An Evidence-Based Review of Recent Data

References

• Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389:1756–1770. doi:10.1016/S0140-6736(16)32126-227914657
   PubMed Web of Science ®Google Scholar
• Burisch J, Munkholm P. The epidemiology of inflammatory bowel disease. Scand J Gastroenterol. 2015;50(8):942–951. doi:10.3109/00365521.2015.101440725687629
   PubMed Web of Science ®Google Scholar
• Molodecky NA, Soon I, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;421:46–54. doi:10.1053/j.gastro.2011.10.001
   Web of Science ®Google Scholar
• Hoivik ML, Solberg IC, Henriksen M, Cvancarova M, Bernklev T. Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study. Gut. 2013;62:368–375. doi:10.1136/gutjnl-2012-30231122717453
   PubMed Web of Science ®Google Scholar
• Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural history of adult ulcerative colitis in population-based cohorts: a systematic review. Clin Gastroenterol Hepatol. 2018;16:343–356. doi:10.1016/j.cgh.2017.06.01628625817
   PubMed Web of Science ®Google Scholar
• Solberg IC, Lygren I, Jahnsen J, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44:431–440. doi:10.1080/0036552080260096119101844
   PubMed Web of Science ®Google Scholar
• Magro F, Gionchetti P, Eliakim R, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis. 2017;11(6):649–670.28158501
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. (1528-0012 (Electronic)). Gastroenterology;146(1):96–109.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–265. doi:10.1053/j.gastro.2011.10.03222062358
   PubMed Web of Science ®Google Scholar
• Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–787. doi:10.1136/gut.2010.22112721209123
   PubMed Web of Science ®Google Scholar
• Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353: 2462–2476. doi:10.1056/NEJMoa05051616339095
   PubMed Web of Science ®Google Scholar
• Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14:329–342. doi:10.1038/nri366124751956
   PubMed Web of Science ®Google Scholar
• Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003 52: 65–70. doi:10.1136/gut.52.1.6512477762
   PubMed Web of Science ®Google Scholar
• Kulkarni AB, Huh CG, Becker D, et al. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci U S A. 1993;15:770–774. doi:10.1073/pnas.90.2.770
   Web of Science ®Google Scholar
• Shouval DS, Biswas A, Goettel JA, et al. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity. 2014;40:706–719. doi:10.1016/j.immuni.2014.03.01124792912
   PubMed Web of Science ®Google Scholar
• Dowty ME, Lin J, Ryder TF, et al. The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab Dispos. 2014;42:759–773. doi:10.1124/dmd.113.05494024464803
   PubMed Web of Science ®Google Scholar
• Soendergaard C, Bergenheim FH, Bjerrum JT, Nielsen OH. Targeting JAK-STAT signal transduction in IBD. Pharmacol Ther. 2018;192:100–111. doi:10.1016/j.pharmthera.2018.07.00330048708
   PubMed Web of Science ®Google Scholar
• FDA. 2019 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf.
   Google Scholar
• Pfizer. EU summary of product characteristics 2019. Available from: https://www.ema.europa.eu/en/documents/variation-report/xeljanz-h-c-4214-x-0005-epar-assessment-report-variation_en.pdf.
   Google Scholar
• XR XX. Highlights of prescribing information; 2019 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf.
   Google Scholar
• Yamaoka K, Saharinen P, Pesu M, Holt VET 3rd, Silvennoinen O, O’Shea JJ. The Janus kinases (Jaks). Genome Biol. 2004;5:253. doi:10.1186/gb-2004-5-12-25315575979
   PubMed Web of Science ®Google Scholar
• Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77:521–546. doi:10.1007/s40265-017-0701-928255960
   PubMed Web of Science ®Google Scholar
• O’Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013;368:161–170. doi:10.1056/NEJMra120211723301733
   PubMed Web of Science ®Google Scholar
• Can G, Tezel A, Gurkan H, et al. Tyrosine kinase-2 gene polymorphisms are associated with ulcerative colitis and Crohn’s disease in Turkish Population. Clin Res Hepatol Gastroenterol. 2015;39:489–498. doi:10.1016/j.clinre.2015.01.00525744728
   PubMed Web of Science ®Google Scholar
• Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3(9):745–756. doi:10.1038/nri118412949498
   PubMed Web of Science ®Google Scholar
• Rovira J, Ramirez-Bajo MJ, Banon-Maneus E, et al. Tofacitinib halts progression of graft dysfunction in a rat model of mixed cellular and humoral rejection. Transplantation. 2018;102:1075–1084. doi:10.1097/TP.000000000000220429620612
   PubMed Web of Science ®Google Scholar
• Changelian PS, Flanagan ME, Ball DJ, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003;302:875–878. doi:10.1126/science.108706114593182
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Jesson MiLi X, Lee JL, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2011;86:4234–4243.
   Web of Science ®Google Scholar
• Boland BS, Sandborn WJ, Chang JT. Update on Janus kinase antagonists in inflammatory bowel disease. Gastroenterol Clin North Am. 2014;43:603–617. doi:10.1016/j.gtc.2014.05.01125110261
   PubMed Web of Science ®Google Scholar
• Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651-62 doi:10.1038/nrm90912209125
   PubMed Web of Science ®Google Scholar
• Hodge JA, Kawabata TT, Krishnaswami S, et al. The mechanism of action of tofacitinib - an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34:318–328.26966791
   PubMed Web of Science ®Google Scholar
• Meyer DM, Jesson MI, Li X, et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond). 2010;7:1476–9255 (Electronic).
   PubMed Web of Science ®Google Scholar
• Krishnaswami S, Boy M, Chow V, Chan G. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers. Clin Pharmacol Drug Dev. 2015;4:83–88. doi:10.1002/cpdd.17127128212
   PubMed Web of Science ®Google Scholar
• Mukherjee A, Hazra A, Smith MK, et al. Exposure-response characterization of tofacitinib efficacy in moderate to severe ulcerative colitis: results from a dose-ranging phase 2 trial. Br J Clin Pharmacol. 2018;84:1136–1145. doi:10.1111/bcp.1352329377257
   PubMed Web of Science ®Google Scholar
• Ma G, Xie R, Strober B, et al. Pharmacokinetic characteristics of tofacitinib in adult patients with moderate to severe chronic plaque psoriasis. Clin Pharmacol Drug Dev. 2018;7: 587–596. doi:10.1002/cpdd.47129856518
   PubMed Web of Science ®Google Scholar
• Gupta P, Alvey C, Wang R, et al. Lack of effect of tofacitinib (CP-690,550) on the pharmacokinetics of the CYP3A4 substrate midazolam in healthy volunteers: confirmation of in vitro data. Br J Clin Pharmacol. 2012;74:109–115. doi:10.1111/bcp.2012.74.issue-122233204
   PubMed Web of Science ®Google Scholar
• Gupta P, Chow V, Wang R, et al. Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects. Clin Pharmacol Drug Dev. 2014;3:72–77. doi:10.1002/cpdd.v3.127128233
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367:616–624. doi:10.1056/NEJMoa111216822894574
   PubMed Web of Science ®Google Scholar
• Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009;60: 1895–1905. doi:10.1002/art.2456719565475
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–1736. doi:10.1056/NEJMoa160691028467869
   PubMed Web of Science ®Google Scholar
• Motoya S, Watanabe M, Kim HJ. et al. Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies. Intest Res;2018 233–245. doi:10.5217/ir.2018.16.2.23329743836
   PubMed Web of Science ®Google Scholar
• Hanauer S, Panaccione R, Danese S, et al. Tofacitinib induction therapy reduces symptoms within 3 days for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17: 139–147. doi:10.1016/j.cgh.2018.07.00930012431
   PubMed Web of Science ®Google Scholar
• Hanauer S, Rubin DT, Gionchetti P. Tofacitinib efficacy in patients with moderate to severe ulcerative colitis: subgroup analyses of OCTAVE induction 1 and 2 and OCTAVE Sustain by 5-aminosalicylates use. Journal of Crohn’s and Colitis. 2019;13 (Supplement_1): S477.doi:10.1093/ecco-jcc/jjy222.836
   Google Scholar
• Reinisch W, Osterman MT, Doherty G, et al.. Efficacy of Tofacitinib Maintenance Therapy for Ulcerative Colitis in Remitting Patients Vs. patients with Clinical Response After 8 Weeks of Induction Treatment. Journal of Crohn’s and Colitis. 2019;13 (Supplement_1): S378–S379. doi:10.1093/ecco-jcc/jjy222.655
   Google Scholar
• Panes J,Bressler B, Colombel JF, et al. Editor Efficacy and safety of tofacitinib retreatment for ulcerative colitis after treatment interruption: results form the octave clinical trials. Digestive diseases week. Gastroenterology. 2019;154.
   Web of Science ®Google Scholar
• Sands BE, Moss AC, Armuzzi A. Efficacy and safety of dose escalation to tofacitinib 10mg BID for patients with ulcerative colitis following loss of response on tofacitinib 5mg BID maintenance therapy: results form OCTAVE open. Digestive Dis Week. 2018;154:S–385.
   Google Scholar
• Rubin DT, Dubinsky MC, Lukas M et al. Long-term efficacy of tofacitinib in patients who received extended induction therapy: results of the OCTAVE open study for tofacitinib delayed responders. Journal of Crohn’s and Colitis. 2019;13 (Supplement_1):S050–S052. doi:10.1093/ecco-jcc/jjy222.077
   Google Scholar
• Chiorean M, Su C, Matsuoka K et al. Efficacy and safety of open-label treatment with tofacitinib 10mg twice daily in patient with ulcerative colitis with clinical response, but not remission, after 52 weeks of maintenance therapy: data from the OCTAVE studies. Journal of Crohn’s and Colitis, 2019;13 (Supplement_1): S049–S050. doi:10.1093/ecco-jcc/jjy222.075
   Google Scholar
• Rubin DT, Travis S, Abraham BP, et al. Maintenance of efficacy following tofacitinib dose reduction in patients with ulcerative colitis in stable remission. Journal of Crohn’s and Colitis. 2019;13 (Supplement_1): S425–S426. doi:10.1093/ecco-jcc/jjy222.743
   Google Scholar
• Dubinsky MC, Bressler B, Armuzzi A et al. Improvement in patient-reported Inflammatory Bowel Disease Questionnaire outcomes, and relationship with disease activity, in tofacitinib treated patient with ulcerative colitis: data form the OCTAVE clinical trials. Journal of Crohn’s and Colitis. 2019;13 (Supplement_1):S462–S463. doi:10.1093/ecco-jcc/jjy222.809
   Google Scholar
• Weisshof R, Aharoni Golan M, Sossenheimer PH, et al. Real-world experience with tofacitinib in IBD at a tertiary center. Dig Dis Sci. 2019;64:1945–1951. doi:10.1007/s10620-019-05492-y30734234
   PubMed Web of Science ®Google Scholar
• Ungaro R, Fenster M, Dimopoulos C, et al. Real-World effectiveness of tofacitinib in ulcerative colitis: a multi-centre study. Journal of Crohn’s and Colitis 2019;13(Supplement_1):S274–S275. doi:10.1093/ecco-jcc/jjy222.468
   Google Scholar
• Lair-Mehiri L, Stefanescu C, Vaysse T, et al. Real-world tofacitinib effectivness and safety in patients with refractory ulcerative colitis . Journal of Crohn’s and Colitis, 2019; 13 (Supplement_1): S478–S479, 10.1093/ecco-jcc/jjy222.839.
   Google Scholar
• Mei WQ, Hu HZ, Liu Y, Li ZC, Wang WG. Infliximab is superior to other biological agents for treatment of active ulcerative colitis: a meta-analysis. World J Gastroenterol. 2015;21:6044–6051. doi:10.3748/wjg.v21.i19.604426019471
   PubMed Web of Science ®Google Scholar
• Bonovas SA-O, Lytras T, Nikolopoulos G, LA-O P-B, Danese SA-O. Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis. Aliment Pharmacol Ther. 2018;47:454–465. doi:10.1111/apt.1444929205421
   PubMed Web of Science ®Google Scholar
• Trigo-Vicente CA-O, Gimeno-Ballester V, Garcia-Lopez S, Lopez-Del Val A. Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis. Int J Clin Pharm. 2018;40:1411–1419. doi:10.1007/s11096-018-0743-430478492
   PubMed Web of Science ®Google Scholar
• Paschos P, Katsoula A, Giouleme O, et al. Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis. Ann Gastroenterol. 2018;31:572–582.30174394
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Panes J, D’Haens GR, et al. Safety of tofacitinib for treatment of ulcerative colitis, based on 4.4 years of data from global clinical trials. Clin Gastroenterol Hepatol. 2019;17(8):1541–1550. doi:10.1016/j.cgh.2018.11.03530476584
   PubMed Web of Science ®Google Scholar
• Winthrop KL, Melmed GY, Vermeire S, et al. Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflamm Bowel Dis. 2018;24:2258–2265. doi:10.1093/ibd/izy13129850873
   PubMed Web of Science ®Google Scholar
• Curtis J Safety and effectiveness of live zoster vaccine in Anti-Tumor Necrosis Factor (TNF) users (VERVE trial); 2019 Available from: https://clinicaltrials.gov/ct2/show/NCT02538341.
   Google Scholar
• Sands BE, Taub PR, Armuzzi A, et al. Tofacitinib treatment is associated with modest and reversible increases in serum lipids in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;30491-4:S1542–S3565. doi:10.1016/j.cgh.2019.04.059
   Web of Science ®Google Scholar
• Sandborn WJ, Panes J, Panaccione R, et al. Tofacitinib for the treatment of ulcerative colitis: up to 5.4 years of safety data from global clinical trials.Journal of Crohn’s and Colitis. 2019;13 (Supplement_1):S344. doi.10.1093/ecco-jcc/jjy222.590
   Google Scholar
• Mahadevan U, Dubinsky MC, Su C, et al. Outcomes of pregnancies with maternal/paternal exposure in the tofacitinib safety databases for ulcerative colitis. Inflamm Bowel Dis. 2018;24:2494–2500. doi:10.1093/ibd/izy16029982686
   PubMed Web of Science ®Google Scholar
• CDC. Update on overall prevalence of major birth defects–atlanta, Georgia, 1978–2005. MMWR Morb Mortal Wkly Rep. 2008;11:1–5.
   Google Scholar
• Clowse MEB, Feldman SR, Isaacs JD, et al. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39:755–762. doi:10.1007/s40264-016-0431-z27282428
   PubMed Web of Science ®Google Scholar
• EMA. Restrictions in use of Xeljanz while EMA reviews risk of blood clots in lungs: EMA; Available from: https://www.ema.europa.eu/en/news/restrictions-use-xeljanz-while-ema-reviews-risk-blood-clots-lungs.
   Google Scholar
• Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114:384–413. doi:10.14309/ajg.000000000000015230840605
   PubMed Web of Science ®Google Scholar
• Olivera P, Danese S, Peyrin-Biroulet L. JAK inhibition in inflammatory bowel disease. Expert Rev Clin Immunol. 2017;13:693–703. doi:10.1080/1744666X.2017.129134228164724
   PubMed Web of Science ®Google Scholar
• Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66:199–209. doi:10.1136/gutjnl-2016-31291227856614
   PubMed Web of Science ®Google Scholar
• Berinstein JA, Steiner CA, Regal RE, et al. Efficacy of induction therapy with high-intensity tofacitinib in 4 patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:988–990. doi:10.1016/j.cgh.2018.11.02230458248
   PubMed Web of Science ®Google Scholar
• Wu B, Wang Z, Zhang Q. Cost-effectiveness of different strategies for the treatment of moderate-to-severe ulcerative colitis. Inflamm Bowel Dis. 2018;24:2291–2302. doi:10.1093/ibd/izy11429718241
   PubMed Web of Science ®Google Scholar
• Milev S, DiBonaventura MD, Quon P, et al. An economic evaluation of tofacitinib for the treatment of moderately-to-severely active ulcerative colitis: modeling the cost of treatment strategies in the United States. J Med Econ. 2019;22: 859–868. doi:10.1080/13696998.2019.160948131012362
   PubMed Web of Science ®Google Scholar
• Dulai PS, Osterman MT, Lasch K, Cao C, Riaz F, Sandborn WJ. Market access analysis of biologics and small-molecule inhibitors for inflammatory bowel disease among US health insurance policies. Dig Dis Sci. 2019;64:2478–2488. doi:10.1007/s10620-019-05594-730923985
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Lopez A, Sandborn W. Head-to-head comparative studies: challenges and opportunities? J Crohns Colitis. 2017;11:S567–S575. doi:10.1093/ecco-jcc/jjw16727660343
   PubMed Web of Science ®Google Scholar