1. At weeks 10 and 58, more patients in the filgotinib 200 mg group experienced clinical remission compared with the placebo group.
2. The proportion of patients with treatment-related side effects was similar between filgotinib 100 mg, filgotinib 200 mg, and placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Ulcerative colitis (UC) is a chronic immune-mediated disease, marked by inflammation of the colon. Although Janus kinase (JAK) inhibitors, such as tofacitinib, have shown promise for treatment of UC, selective JAK-inhibitors may potentially offer comparable efficacies with fewer side-effects. While filgotinib, a JAK1-selective inhibitor, has demonstrated efficacy in conditions such as rheumatoid arthritis and ankylosing spondylitis, its efficacy for UC is uncertain. This randomized controlled trial aimed to assess the efficacy and safety of filgotinib in inducing and maintaining remission for patients with UC. Primary outcome for this study was clinical remission at weeks 10 and 58, defined by total Mayo Clinic Score (MCS), while key secondary outcomes included endoscopic, histologic, and 6-month corticosteroid-free remission. Safety was assessed in all patients receiving one or more dose of filgotinib within induction and maintenance studies. Compared to placebo, filgotinib 200 mg greatly induced and maintained clinical remission at weeks 10 and 58 in patients with moderate-to-severe UC. A longer follow-up would better inform best practices in the management of ulcerative colitis, a chronic inflammatory condition. Nevertheless, this study provided valuable insight into the use of filgotinib 200 mg once daily for management of UC.
Click to read the study in The Lancet
Relevant Reading: Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis
In-depth [randomized controlled trial]: Between Nov 14, 2016, and Mar 31, 2020, 2040 patients were assessed for eligibility at 341 study centers in 40 countries. Included patients were aged 18-75 years with moderate-to-severe UC for ≥ 6 months (total Mayo Clinic Score 6-12). Those who previously received any JAK inhibitor were excluded. Altogether, 625 patients in induction study A (237 in filgotinib 200 mg, 260 in filgotinib 100 mg, and 128 in placebo) and 635 patients in induction study B (242 in filgotinib 200 mg, 265 in filgotinib 100 mg, and 128 in placebo) completed study to week 10. Baseline characteristics were similar between treatment groups.
The primary outcome of clinical remission was greater for filgotinib 200 mg than placebo. This was true at week 10 (induction study A: 26.1% vs. 15.3%, 95% confidence interval [CI] 2.1-19.5, p=0.0157; induction study B: 11.5% vs. 4.2%, 95% CI 1.6-12.8, p<0.05) and week 58 (37.2% in filgotinib 200 mg vs. 11.2% in placebo, 95% CI 16.0-35.9, p<0.05) from baseline. When comparing clinical remission between filgotinib 100 mg and placebo, the difference was not significant at week 10 (p=0.33). However, by week 58, a significant difference was noted between groups, favouring filgotinib 100 mg (23.8% vs. 13.5%, 95% CI 0.0-20.7, p<0.05). The incidence of serious adverse events and adverse events of interest was similar between the three groups (4.3% for filgotinib 200 mg vs. 5.0% for filgotinib 100 mg vs. 4.7% for placebo). Findings from this study suggest that filgotinib 200 mg is more effective than filgotinib 100 mg and placebo for clinical remission in patients with moderate-to-severe ulcerative colitis.
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