- Sandborn W, et al. Oral Rilecitinib and Brepocitinib in Patients With Moderate to Severe Active Ulcerative Colitis: Data From the VIBRATO Umbrella Study. OP045, UEG Week 2021 Virtual Congress, 3-5 October.
According to the authors, combinations of subtype JAK inhibitors could offer an improved benefit-risk profile for patients with various autoimmune diseases. In the phase 2b VIBRATO study (NCT02958865), ritlecitinib, an oral JAK3/TEC inhibitor, and brepocitinib, an oral TYK2/JAK1 inhibitor, are assessed for their efficacy and safety in moderately to severely, active UC patients who showed an inadequate response to corticosteroids, immunosuppressants, or biologic therapies1.
Patients (n=318) were randomised to 20 mg, 70 mg, or 200 mg of ritlecitinib (oral, once daily), 10 mg, 30 mg, or 60 mg of brepocitinib (oral, once daily), or placebo. After 8 weeks all participants were randomised to 30 mg or 50 mg brepocitinib. The 8-week results were presented by Dr William Sandborn (University of California San Diego, CA, USA). Clinical remission was achieved more often in participants in the ritlecitinib 70 mg (28.6%, P=0.0027) and 200 mg (34.0%, P=0.0010) conditions compared with placebo receivers (0%).
Similarly, clinical remission rates were higher for patients receiving brepocitinib 30 mg (25.5%, P=0.0043) or 60 mg (23.4%, P=0.0055) than for placebo receivers (0%). Moreover, for all ritlecitinib and brepocitinib conditions, the proportions of subjects achieving modified clinical remission or endoscopic improvement were significantly higher than in the placebo condition. The safety data showed that 4.4% of the participants discontinued the study due to adverse events (AEs).
In total, 45.7% of the patients experienced AEs (placebo: 52.0%, ritlecitinib: 42.7%, brepocitinib: 47.9%) and no dose-related effects were observed in either experimental group. Most AEs were mild (n=230), or moderate (n=70), but some serious AEs (n=10) were reported. The most common AEs were infections and infestations (n=39), gastrointestinal complaints (n=30), and nervous system disorders (n=26). Infections and infestations were more frequently reported in the brepocitinib (17.6%) and ritlecitinib (8.7%) groups compared with placebo receivers (4.0%).