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P394. Rate of and response to dose escalation in patients treated with adalimumab for moderately to severely active ulcerative colitis: subanalysis of ULTRA 2

D. Wolf1, G. D'Haens2, W. Sandborn3, J.-F. Colombel4, G. Van Assche5, A. Lazar6, Q. Zhou7, A. Robinson7, J. Chao7, R. Thakkar7, 1Atlanta Gastroenterology Associates, Atlanta, United States, 2Academic Medical Center, Amsterdam, Netherlands, 3University of California San Diego, La Jolla, United States, 4Centre Hospitalier Universitaire de Lille, Lille, France, 5University of Toronto, Toronto, Canada, 6AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, 7Abbott Laboratories, Abbott Park, United States

Background

To determine the incidence of and outcomes following dose escalation for adult patients (pts) with moderately to severely active ulcerative colitis (UC) failing conventional therapy enrolled in the 52-week (wk) clinical trial, ULTRA 2 [1].

Methods

In ULTRA 2, pts were randomised 1:1 to receive placebo (PBO) or adalimumab (ADA) 160/80 mg at wks0/2, then ADA 40 mg every other week (eow). Concomitant UC-related medications were maintained at stable doses, except corticosteroids, which could be tapered beginning at wk8. Response at wk8 was assessed in ADA pts using the partial Mayo score ([PMS], Mayo score without endoscopy subscore; response = PMS decrease ≥2 points and ≥30% from baseline, and decrease in rectal bleeding score [RBS] of ≥1 or absolute RBS of 0 or 1). Per protocol, pts with inadequate response could move to open-label (OL) ADA (40 mg eow) at or after wk12, then to OL weekly (ew) for continued inadequate response. Remission (full Mayo score ≤2 with no subscore >1), response (decrease in full Mayo score ≥3 points and ≥30%, with RBS criteria as above), and mucosal healing (endoscopy subscore 0 or 1) were assessed at wk52 for ADA-treated pts who moved to ew ADA. Pts were grouped according to a response at wk8 (yes/no) per PMS, using observed analysis for pts still in the study at wk52, and NRI (non-responder imputation) for all pts who dose-escalated, with those not in the study at wk52 considered not to have efficacy.

Results

123 of 248 ADA-treated pts (49.6%) responded to ADA at wk8 per PMS. Of the wk8 responders, 20 (16.3%) moved to ew dosing during the study; 6/20 (30.0%) had previous anti-TNF exposure. Of the 125 wk8 non-responders, 48 (38.4%) moved to ew dosing; 26/48 (54.2%) had previous anti-TNF exposure. Remission, response, and mucosal healing at wk52 are shown for pts who moved to ew ADA (Table).

Table: Clinical outcomes in patients with dose escalation
 Wk8 responders (N = 20)Wk8 non-responders (N = 48)
 nObservedNRInObservedNRI
Remission428.6%20.0%13.7%2.1%
Response964.3%45.0%1244.4%25.0%
Mucosal healing964.3%45.0%1450.0%29.2%

Conclusion

EW ADA dosing may be a beneficial treatment strategy for some UC pts. Pts responding to induction therapy at wk8 achieved meaningful rates of clinical remission, response, and mucosal healing at wk52 with ew dosing. Likewise, clinical response and mucosal healing occurred in some wk8 non-responders with ew ADA dosing.

1. Sandborn WJ, et al. Gastroenterology. 2012; 142:257.