Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

Abstract

Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions: These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

Integrated safety analysis of filgotinib for ulcerative colitis: Results from SELECTION and SELECTIONLTE

“…High rates per 100 PYE of HZ have been reported in Asian patients with UC treated with tofacitinib (IR: 6.5) and upadacitinib (EAIR: 10.7 [15 mg] and 17.0 [30 mg]) 32,35 . In a post hoc analysis of the phase 2b/3 SELECTION study including 102 Japanese patients, no new safety signals were noted and AEs, including HZ, occurred at similar frequencies in Japanese patients compared with the overall SELECTION population 36 …”

“…32,35 In a post hoc analysis of the phase 2b/3 SELECTION study including 102 Japanese patients, no new safety signals were noted and AEs, including HZ, occurred at similar frequencies in Japanese patients compared with the overall SELECTION population. 36 Patients with IBD have a 2-3-fold increased risk of thromboembolic events, such as deep vein thrombosis and pulmonary embolism, compared with the general population, highlighting the importance of monitoring this potential risk. 37 In the current analysis, thromboembolic events were limited in number and the rates were similarly low in the placebo and FIL groups, with no indication of an enhanced risk in patients receiving either FIL dose.…”

Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

“…The I-CARE (Inflammatory Bowel Disease Cluster for Assessment of Risk and Epidemiology) initiative is an important collaborative effort involving 15 countries and over 10,000 IBD patients to investigate the risks associated with IBD therapy, particularly biological therapies. It represents a significant step forward in understanding the risks and benefits associated with IBD therapy, particularly with respect to newer biological agents [ 112 ]. The data generated by this initiative will help inform clinical decision making and ultimately improve patient outcomes.…”

The role and prospect of tofacitinib in patients with ulcerative colitis

“…For more than a decade, anti-TNFs were the only biologics approved for patients with UC; however, newer medication with different mechanisms of action are now available. 1,2 Vedolizumab, a monoclonal antibody targeting α4β7 integrin, was shown to exhibit significant clinical response and remission in moderate to severe UC compared to placebo in the GEMINI trial. 3,4 Ustekinumab, a monoclonal antibody that targets the p40 subunit shared by interleukin-12 and -23, was also confirmed to be effective in the UNIFI trial.…”

“…With the advent of anti-tumor necrosis factor (anti-TNF) therapy, a dramatic change occurred in the treatment and prognosis of IBD. For more than a decade, anti-TNFs were the only biologics approved for patients with UC; however, newer medication with different mechanisms of action are now available [ 1 , 2 ]. Vedolizumab, a monoclonal antibody targeting α4β7 integrin, was shown to exhibit significant clinical response and remission in moderate to severe UC compared to placebo in the GEMINI trial [ 3 , 4 ].…”