Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial

Vermeire, Séverine; Schreiber, Stefan; Robert, Philippe; Kuehbacher, Tanja; Hébuterne, Xavier; Roblin, Xavier; Kłopocka, Maria; Goldiş, Adrian; Wiśniewska-Jarosińska, Maria; Baranovsky, A. Yu.; Sike, Róbert; Stoyanova, Kremena; Tasset, Chantal; Aa, Annegret Van der; Harrison, P.

doi:10.1016/s0140-6736(16)32537-5

Cited by 366 publications

(272 citation statements)

References 29 publications

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“…Four in 152 patients (3%) receiving the drug experienced a serious infection versus none in the placebo group. Similar incidences in early discontinuations and serious adverse events were observed, with the majority related to worsening of disease 17. A phase II trial evaluating the efficacy of another selective JAK1 inhibitor in CD (ABT-494, AbbVie, Chicago, Illinois, USA) is currently ongoing, but has yet to report any results.…”

Section: Discussionmentioning

confidence: 69%

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

Vries¹,

Ludbrook

Hicks

et al. 2017

BMJ Case Reports

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Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC. The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.

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Section: Discussionmentioning

confidence: 69%

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

Vries¹,

Ludbrook

Hicks

et al. 2017

BMJ Case Reports

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“…Rates of mucosal healing were 4 versus 2% in the filgotinib and placebo group, respectively, after 10 weeks. Further phase III studies will have to confirm these findings and evaluate the efficacy of filgotinib in maintenance settings [45].…”

Section: Filgotinibmentioning

confidence: 95%

Current and Future Targets for Mucosal Healing in Inflammatory Bowel Disease

Atreya

Neurath

2017

Visc Med

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The induction and subsequent maintenance of mucosal healing has emerged as one of the central therapeutic goals in the management of patients with inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). Current and novel treatment options are assessed regarding their therapeutic efficacy on the basis of their ability to induce mucosal healing. However, there is still substantial debate about the precise definition of mucosal healing. Here, we will give an overview regarding the definitions of mucosal healing as well as its probable effects on long-term disease behavior and finally focus on current and potential therapeutic targets to achieve this therapeutic goal in IBD patients.

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“…In a randomized, double-blinded phase II trial, filgotinib was effective in the induction of clinical remission, but it failed to reach an endoscopic improvement ( n = 174). Filgotinib seems to increase the risk of infections [65]. Two phase III studies are currently recruiting patients for further investigation of therapeutic and potential side effects (NCT02914600, NCT02914561).…”

Section: New Substances In the Pipeline – Reason To Hopementioning

confidence: 99%

Treatment Perspectives in Crohn’s Disease

Vetter¹

2018

Digestion

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Background: Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Summary: Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy.

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Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial

Cited by 366 publications

References 29 publications

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis

Current and Future Targets for Mucosal Healing in Inflammatory Bowel Disease

Treatment Perspectives in Crohn’s Disease

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