UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS
Authors: Hassan Syed Adeel , Perry Courtney , Flomenhoft Deborah , Richardson Brooks , Kapur Neeraj , Berinstein Jeffrey , Barrett Terrence 
Published: January 2024

Abstract

INTRODUCTION
Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC.

METHODS
ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or &gt; 2 BM and CRP &gt; 45 mg/L. IP response was defined as ≤ 4 BM and CRP &lt; 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) &lt;250 ug/g or CRP &lt;5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen.

RESULTS
Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage.

CONCLUSION
We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy.

Table 1 Baseline Disease Characteristics

Table 2 Patient Specific Inpatient Therapy

Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks

Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline