S0897 Efficacy and Safety of Combining Tofacitinib With a Biologic in Patients With Refractory Inflammatory Bowel Diseases

INTRODUCTION: We aimed to examine the efficacy and safety of combination therapy with a biologic and tofacitinib, an oral small molecule Janus kinase inhibitor in pts with refractory inflammatory bowel diseases (IBD). METHODS: A retrospective cohort of IBD pts on combination therapy (tofacitinib and a biologic) from 3 referral centers were included. The primary outcome was a clinical response ( >25% reduction in symptoms) at week 8 or 16 determined by physician global assessment. The secondary outcome was the resolution of mucosal ulceration in pts with endoscopy before and after initiation of combination therapy. Adverse events (AEs) including any abnormal lipid profile or surgical complications were recorded. RESULTS: A total of 42 IBD pts were analyzed (Table 1), a majority (26, 61.9%) with Ulcerative colitis (UC) with a median follow-up of 5 months of combination therapy. A majority (26, 63.4%) had failed at least two biologics prior to starting combination therapy. Most common biologic in combination therapy was vedolizumab (6 CD, 21 UC) followed by ustekinumab (8 CD), infliximab (1 CD, 5 UC) and certolizumab pegol (1 CD) (Figure 1a). Tofacitinib induction dosing was 10mg BID in 39 pts (93%). Seventeen pts (40.5%) were on concomitant steroids and 3 (7.1%) on an immunomodulator at the start of combination therapy. In regard to efficacy (Figure 1b), by 8/16 weeks, 26 pts (66.7%) had achieved clinical response with 3 in remission and 13 patients (33.3%) with no response. Endoscopic assessment of mucosal ulceration (before vs. after) showed a trend towards significance (n = 24; 83% vs. 58%; P = 0.07) (Figure 1c). There was a non-significant drop in CRP with combination therapy (n = 21; mean, 17 vs. 7.3; P = 0.33) (Figure 1d). No baseline variable was significantly associated with clinical response (Table 2). AEs were reported in 4 pts (1 CD, 3 UC), with the CD pt discontinuing tofacitinib because of headaches and itchiness. Other AEs reported included: headache, rash, candida esophagitis. Only 1 out of 24 pts with complete lipid data developed a new abnormal lipid profile at week 8/16 and none were initiated on statins. No DVT or herpes zoster reactivation was reported. Seven UC pts underwent surgery within 2 weeks of a tofacitinib dose with 4 experiencing at least one Clavien-Dindo grade complication. CONCLUSION: Tofacitinib when combined with a biologic is effective at inducing a clinical response in refractory UC and CD pts with safety signals similar to use as tofacitinib monotherapy.Figure 1Table 1Table 2