Effectiveness and Safety of Combining Tofacitinib With a Biologic in Patients With Refractory Inflammatory Bowel Diseases.

ABSTRACT AND KEY WORDS Background One therapeutic option with limited data among patients with active moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) despite biologic monotherapy is using a combination of a biologic with Tofacitinib (TBT). Our aim was to examine the effectiveness and safety of TBT in this subset of patients. Methods Data of IBD patients at 2 referral centers on TBT were extracted. The primary outcome was clinical response (>50% reduction in symptoms) at week 8 and/or 16 determined by Physician Global Assessment. Secondary outcome was clinical remission (resolution of symptoms), corticosteroid-free clinical response and remission, normalization of CRP and endoscopic/radiographic response and remission. Adverse events (AEs) including any abnormal lipid profile or surgical complications were also assessed. Results Thirty-five patients (25UC, 10CD) were included. Biologics combined with tofacitinib were vedolizumab (68.6%), ustekinumab (17.1%), and infliximab (14.3%) and the median follow-up duration was 4 months. A majority (57.2%) had failed at least two biologics prior to starting TBT. At weeks 8 and/or 16, 37.1% achieved clinical response with 5.7% in clinical remission. Among the 23 patients with endoscopically/radiographically active disease at baseline, 56.5% had endoscopic/radiographic response and 34.8% achieved remission. Three AEs occurred in 2 (5.7%) patients, with an IR of 20.5 (15.0–47.2)/100PYF. No VTE and herpes zoster was reported. Conclusions TBT is effective at inducing endoscopic/radiographic response and a modest clinical response in UC and CD patients with active clinical symptoms despite prior biologic monotherapy. No new safety signals were detected beyond those reported with tofacitinib monotherapy.