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Clinical Trial
, 109 (11), 1771-80

Four-year Maintenance Treatment With Adalimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Data From ULTRA 1, 2, and 3

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Clinical Trial

Four-year Maintenance Treatment With Adalimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Data From ULTRA 1, 2, and 3

Jean-Frederic Colombel et al. Am J Gastroenterol.

Abstract

Objectives: The safety and efficacy of adalimumab for patients with moderately to severely active ulcerative colitis (UC) has been reported up to week 52 from the placebo-controlled trials ULTRA (Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab) 1 and 2. Up to 4 years of data for adalimumab-treated patients from ULTRA 1, 2, and the open-label extension ULTRA 3 are presented.

Methods: Remission per partial Mayo score, remission per Inflammatory Bowel Disease Questionnaire (IBDQ) score, and mucosal healing rates were assessed in adalimumab-randomized patients from ULTRA 1 and 2 up to week 208. Corticosteroid-free remission was assessed in adalimumab-randomized patients who used corticosteroids at lead-in study baseline. Maintenance of remission per partial Mayo score and mucosal healing was assessed in patients who entered ULTRA 3 in remission per full Mayo score and with mucosal healing, respectively. As observed, last observation carried forward (LOCF) and nonresponder imputation (NRI) were used to report efficacy. Adverse events were reported for any adalimumab-treated patient.

Results: A total of 600/1,094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and included in the intent-to-treat analyses of the studies. Of these, 199 patients remained on adalimumab after 4 years of follow-up. Rates of remission per partial Mayo score, remission per IBDQ score, mucosal healing, and corticosteroid discontinuation at week 208 were 24.7%, 26.3%, 27.7% (NRI), and 59.2% (observed), respectively. Of the patients who were followed up in ULTRA 3 (588/1,094), a total of 360 patients remained on adalimumab 3 years later. Remission per partial Mayo score and mucosal healing after ULTRA 1 or 2 to year 3 of ULTRA 3 were maintained by 63.6% and 59.9% of patients, respectively (NRI). Adverse event rates were stable over time.

Conclusions: Remission, mucosal healing, and improved quality of life were maintained in patients with moderately to severely active UC with long-term adalimumab therapy, for up to 4 years. No new safety signals were reported.

Figures

Figure 1
Figure 1
Patient enrollment in the ULTRA studies. (a) Patient flow into ULTRA 3. ADA, adalimumab; EOW, every other week; EW, weekly; OL, open label; ULTRA, Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab. One patient in ULTRA 2 was randomized to adalimumab but did not receive the study drug. (b) The number of patients by study visit in the ADA Randomized Set and the ADA Extension Set. DB, double blind; PBO, placebo.
Figure 2
Figure 2
Long-term remission and mucosal healing rates with adalimumab treatment. (a) Proportion of patients with remission per partial Mayo score over time in the ADA Randomized Set (N=600). Gray bars indicate all patients randomized to adalimumab at lead-in study baseline (All, NRI); black bars indicate patients randomized to every other week adalimumab dosing imputing no remission for patients who escalated to weekly dosing (no dose escalation, mNRI). (b) Proportion of patients with mucosal healing over time in the ADA Randomized Set (N=600), NRI analysis. (c) Maintenance of remission per partial Mayo score in patients who entered ULTRA 3 in remission per full Mayo score from the ADA Extension Set (N=242). Black bars indicate LOCF and gray bars indicate NRI analysis. (d) Maintenance of mucosal healing in patients who entered ULTRA 3 with mucosal healing from the ADA Extension Set (N=409). Black bars indicate LOCF and gray bars indicate NRI analysis. ADA, adalimumab; LOCF, last observation carried forward; mNRI, modified nonresponder imputation; NRI, nonresponder imputation; ULTRA, Ulcerative Colitis Long-Term Remission and Maintenance with Adalimumab.
Figure 3
Figure 3
Discontinuation of corticosteroids over time in patients who used corticosteroids at lead-in study baseline from the adalimumab (ADA) Randomized Set (N=356). As-observed analysis.
Figure 4
Figure 4
Proportion of patients with remission per IBDQ score (IBDQ ≥170) over time in the ADA Randomized Set (N=600). NRI analysis. ADA, adalimumab; IBDQ, Inflammatory Bowel Disease Questionnaire; NRI, nonresponder imputation.

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