ABSTRACT
Introduction: There are scant data on long-term outcomes of treatment of inflammatory bowel disease (IBD) with a combination of advanced therapies, including after de-escalation. Method(s): We identified patients with IBD at a tertiary center who began therapy with vedolizumab (VDZ) in combination with another advanced therapy (biologic or JAK inhibitor) between 2016 and 2020 and examined their outcomes through 6/1/22. We defined biochemical remission as CRP, 5 mg/L and calprotectin < 150 mcg/g, and endoscopic remission as Mayo endoscopic subscore 0 or simple endoscopic score for Crohn's disease (CD) 0. Short-term outcomes of this cohort were previously reported. Result(s): Fourteen patients with a median of 322 (IQR 251-322) weeks of follow up were identified. 10 had ulcerative colitis, 3 CD, and 1 indeterminate colitis. VDZ was combined with tofacitinib in 9 patients, ustekinumab in 3 and adalimumab in 2. Median time on combination therapy was 94 weeks (IQR 17-133). Eight patients achieved objective remission (3 biochemical, 5 endoscopic), 1 changed combination with subsequent endoscopic remission, 2 had primary non-response, 1 had secondary non-response, 1 stopped within 1 month due to reported adverse effect (paresthesia), and 1 lacked follow-up data. Eight patients de-escalated to a single agent, 4 at physician direction and 4 due to insurance denial. Before de-escalation, 6 had objective remission (2 biochemical, 4 endoscopic). After de-escalation, 3 patients maintained objective remission (2 biochemical, 1 endoscopic), 3 had disease flare, of which 1 required colectomy, and 2 lacked data. All 3 patients with disease flare had de-escalated following an insurance denial. Two patients remained on combination therapy through follow up: 1 has endoscopic remission after changing one drug of their combination and 1 has ongoing moderate endoscopic disease despite combination therapy. There were 2 infections requiring hospitalization (rotavirus, C. difficile), and 8 non-serious infections (5 mild SARS-COV-2, 1 peristomal cellulitis, 1 pneumonia, 1 sinus) while on combination therapy. Conclusion(s): In long-term follow up of this small cohort, there were no new signals on effectiveness or safety of combining advanced agents. De-escalation to a single agent was tolerated in half of patients with follow-up data;all patients who flared following de-escalation had adjusted therapy due to insurance denial. More data is needed to inform de-escalation decisions.