Induction and maintenance of clinical remission by interferon-β in patients with steroid-refractory active ulcerative colitis-an open long-term pilot trial

Abstract Aims The SELECTION (NCT02914522) Induction Studies evaluated the efficacy/safety of filgotinib (FIL), a preferential JAK1 inhibitor, as induction therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who were biologic-naïve but failed conventional therapy (Induction Study A) or failed prior biologics (Induction Study B). Methods Pts were randomized 2:2:1 to once–daily FIL 200mg, FIL 100mg or placebo (PBO). The primary (clinical remission), key secondary (Mayo Clinic Score [MCS] remission, endoscopic remission, and histologic remission), and exploratory endpoints (MCS response and endoscopic improvement) were assessed at Week 10. Results In both studies, baseline demographics and disease characteristics were similar across treatment groups. In Study A, 659 pts were randomized and treated. Baseline mean MCS was 8.6 and 56% had a Mayo endoscopic subscore (ES)=3. A significantly higher proportion of biologic-naïve pts on FIL 200mg achieved clinical remission vs PBO and all key secondary endpoints (Table). In Study B, 689 pts were randomized and treated. Baseline mean MCS was 9.3 and 78% had ES=3. Prior treatment failures were: anti-TNF (86%), vedolizumab (52%) and both (dual-refractory; 43%). A significantly higher proportion of biologic-experienced pts on FIL 200mg achieved clinical remission vs PBO. In Studies A and B, a greater proportion of pts on FIL 200 mg achieved an MCS response and endoscopic improvement vs PBO. The rates of AEs, serious AEs and discontinuations due to AEs were similar across FIL and PBO groups during induction. In the PBO, FIL 100mg and FIL 200mg groups, serious infections occurred in 0.7%, 0.7% and 0.4% pts in Study A and 1.4%, 1.4% and 0.8% pts in Study B; H Zoster occurred in <1% in both groups for both cohorts. Conclusions SELECTION included a high proportion of dual-refractory pts, and pts with severe endoscopic disease. Both doses of FIL were well tolerated. Filgotinib 200mg was effective induction therapy for both biologic-naïve/-experienced pts with moderately to severely active UC. Funding Agencies None

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Long-term Outcomes in Steroid-refractory Ulcerative Colitis Treated with Tacrolimus Alone or in Combination with Purine Analogues

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjv175 ◽

2015 ◽

Vol 10 (1) ◽

pp. 31-37 ◽

Cited By ~ 13

Author(s):

K. J. Schmidt ◽

N. Müller ◽

A. Dignass ◽

D. C. Baumgart ◽

H. Lehnert ◽

...

Keyword(s):

Ulcerative Colitis ◽

Long Term Outcomes ◽

Purine Analogues ◽

Steroid Refractory

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Long-term efficacy and safety of once-daily mesalazine granules for the treatment of active ulcerative colitis

Clinical and Experimental Gastroenterology ◽

10.2147/ceg.s35691 ◽

2014 ◽

pp. 369 ◽

Cited By ~ 12

Author(s):

Stephan Böhm ◽

Wolfgang Kruis

Keyword(s):

Ulcerative Colitis ◽

Active Ulcerative Colitis ◽

Efficacy And Safety ◽

Once Daily ◽

Term Efficacy

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P307. Safety, efficacy, and pharmacokinetics of golimumab in patients with moderately to severely Active ulcerative colitis: PURSUIT-SC long-term extension

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjw019.426 ◽

2016 ◽

Vol 10 (suppl 1) ◽

pp. S248-S249

Keyword(s):

Ulcerative Colitis ◽

Active Ulcerative Colitis

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A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

Gastroenterology Research and Practice ◽

10.1155/2016/3162595 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Katsuya Endo ◽

Motoyuki Onodera ◽

Hisashi Shiga ◽

Masatake Kuroha ◽

Tomoya Kimura ◽

...

Keyword(s):

Ulcerative Colitis ◽

Therapeutic Efficacy ◽

Maintenance Treatment ◽

Remission Rate ◽

Rank Test ◽

Clinical Response Rate ◽

Therapeutic Outcomes ◽

Significant Difference ◽

Steroid Refractory

Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC.Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX(n=48)or Tac(n=47)in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups.Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test). The proportions of serious adverse events did not differ between the groups.Conclusion.The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

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