Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

Sandborn, William J.; Su, Chinyu; Sands, Bruce E.; D’Haens, Geert R.; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G.; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary S.; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah A.; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul J.; Panés, Julián

doi:10.1056/nejmoa1606910

Cited by 1,362 publications

(1,272 citation statements)

References 24 publications

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“…Inflammatory bowel disease (IBD) refers to a collection of disorders manifested by inflammation of the small intestine and colon, including ulcerative colitis (UC) and CD. In patients with moderately to severely active UC, tofacitinib was found to be more effective as induction and maintenance therapy than placebo and is now approved for this disease . Curiously, efficacy in CD has been less consistent .…”

Section: A Brief Survey Of Approved and Late Phase Jakinibsmentioning

confidence: 99%

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Gadina

Johnson

Schwartz

et al. 2018

Journal of Leukocyte Biology

130

100

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In this era, it is axiomatic that cytokines have critical roles in cellular development and differentiation, immune homeostasis, and host defense. Equally, dysregulation of cytokines is known to contribute to diverse inflammatory and immune-mediated disorders. In fact, the past 20 years have witnessed the rapid translation of basic discoveries in cytokine biology to multiple successful biological agents (mAbs and recombinant fusion proteins) that target cytokines. These targeted therapies have not only fundamentally changed the face of multiple immune-mediated diseases but have also unequivocally established the role of specific cytokines in human disease; cytokine biologists have many times over provided remarkable basic advances with direct clinical benefit. Numerous cytokines rely on the JAK-STAT pathway for signaling, and new, safe, and effective small molecule inhibitors have been developed for a range of disorders. In this review, we will briefly summarize basic discoveries in cytokine signaling and briefly comment on some major unresolved issues. We will review clinical data pertaining to the first generation of JAK inhibitors and their clinical indications, discuss additional opportunities for targeting this pathway, and lay out some of the challenges that lie ahead.

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Section: A Brief Survey Of Approved and Late Phase Jakinibsmentioning

confidence: 99%

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Gadina

Johnson

Schwartz

et al. 2018

Journal of Leukocyte Biology

130

100

View full text Add to dashboard Cite

show abstract

“…Early results as a treatment for ulcerative colitis look promising, including evidence of mucosal healing. [246][247][248][249] The results in Crohn's disease have not been as robust, perhaps because of reliance on CDAI for outcome measurement and a high placebo response, but the data for maintenance of remission still seem positive. 250 251 Another JAK1 inhibitor, filgotinib, has been reported to be superior to placebo in inducing remission in patients with moderate to severe Crohn's disease.…”

Section: Resultsmentioning

confidence: 99%

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

Cohen

Sachar

2017

BMJ

115

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The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

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“…128 The first in class tofacitinib is a non-selective JAK inhibitor (though it preferentially inhibits JAK 1 and JAK 3) that is already approved for use in rheumatoid arthritis. 129,130 The phase 3 OCTAVE studies of tofacitinib in moderate-to-severe UC confirmed its efficacy as both an induction and maintenance agent, 131 and it is currently under review by the FDA. There are other JAK inhibitors under development, most notably the JAK-1 selective filgotinib 132 and upadacitinib, 133 which have shown phase 2b efficacy in CD.…”

Section: What Is On the Horizonmentioning

confidence: 99%

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

et al. 2018

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The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

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Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

Cited by 1,362 publications

References 24 publications

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

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