REAL WORLD DURABILITY OF RESPONSE AND REMISSION WITH UPADACITINIB IN ULCERATIVE COLITIS: A MULTICENTER STUDY

Abstract BACKGROUND We aimed to describe the real-world durability of clinical and endoscopic outcomes of upadacitinib (UPA) in ulcerative colitis (UC). METHODS We retrospectively analyzed an ongoing multi-center cohort of UC patients (pts) in the United States who were started on UPA for active disease. Primary outcome was clinical remission at 1-yr assessed by partial Mayo score (resolution of all UC related symptoms and physician global assessment). Secondary outcomes assessed at various timepoints, including after re-escalation, included clinical response (>50% reduction in symptoms utilizing the partial Mayo score), endoscopic response (Mayo endoscopic score ≤1 or absence of erosions/ulcerations) and histological remission (defined as normal or chronic inactive). Durable secondary outcomes achieved at both 6 months and at 1 year and beyond were also assessed. Descriptive statistics were performed. Adverse events (AEs) investigated included cardiovascular events and herpes zoster (HZ). RESULTS 416 pts were included (Table 1) with median values for age at initiation of 36.00 yrs (range 27-48), disease duration 7.00 yrs (range 3-14) and follow-up 993 days (IQR, 672-1103), with 206 (49.52%) with follow-up at 1 yr or beyond. Of these, 66.1% had extensive colitis. Induction duration was 8 wks in 86.5% and 16 wks in 4.8% (20/416). Most received an induction dose of 45mg (97.1%) and maintenance dose of 30 mg (85.8%). Among the evaluable population at 1 year and beyond, 62.5% (45/80) were in clinical remission, 75.9% (22/29) in endoscopic response with 58.6% (17/29) in remission and 66.6% (20/30) in histological remission. At 6 months, clinical remission was 51.6% (42/93), endoscopic response was 75% (24/32) of which 43.75% (14/32) were in remission and histologic remission was seen in 40.8% (20/49). Durable secondary outcomes of clinical remission were seen in 71.4% (30/42), endoscopic improvement in 45.8% (11/24), and histologic remission in 35% (7/20). Re-escalation to 45 mg occurred in 35 pts, of which 48.6% (17/35) were re-escalated due to incomplete induction clinical response with all achieving response (11 in remission). The rest (18/35) were re-escalated for clinical relapse after initial remission where 72.2% (13/18) were able to recapture remission. After re-escalation, 54.3% (19/35) continued on 45mg daily. AEs were reported in 12.7% with HZ in 7 pts (2.1%). One pt aged 53 yrs had an episode of TIA after 1 yr on UPA at 15 mg, without pre-existing cardiovascular risk factors and UPA use is ongoing at the same dose. There were no reported episodes of worsening of pre-existing cardiovascular disease or DVT/PE. CONCLUSION UPA is durably effective and safe in a real-world clinical setting with re-escalation to 45 mg capturing response in a majority of the pts. Ongoing recruitment will provide further evidence on long term effectiveness and safety.