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

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.

Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice

“…The basis for these findings may be the presence of several Bio/Tac naïve patients in our study, as these patients showed a high clinical response rate (86.7%) at 12 weeks. In a follow-up study of the UL-TRA 1, 2, and 3 trials, Colombel et al [15] reported that the long-term remission rate at 208 weeks was 24.7%. In our study, the remission rate at both 200 and 350 weeks was 30%, indicating good remission rates beyond 6 years.…”

“…The ULTRA 2 trial demonstrated efficacy for adalimumab in the maintenance of remission following 52 weeks of treatment. Additionally, in the UL-TRA 3 trial, which included patients who achieved remission at 156 weeks and were evaluated using the partial Mayo score, up to 78.5% of the treated patients maintained remission for 4 years [15]. Recently, results for 4 years of adalimumab maintenance therapy in patients with UC were reported in Japan [16].…”

Promising biological therapies for ulcerative colitis: A review of the literature

“…Patients were randomly assigned to receive tofacitinib at a dose of 0.5, 3, 10 or 15 mg or placebo twice daily for 8 wk [21] . The primary outcome, clinical response at 8 wk, occurred in 32%, 48%, 61% and 78% of patients receiving tofacitinib at a dose of 0.5 mg (P = 0.39), 3 mg (P = 0.55), 10 mg (P = 0.10), [18] 360 40 mg sc every other week 208 63.6% remission per partial Mayo score at week 208 Golimumab PURSUIT-SC [20] 253 200/100 mg sc 2 wk apart 6 51.6% (P < 0.0001) clinical response at week 6 17.8% (P < 0.0001) clinical remission at week 6 257 400/200 mg sc 2 wk apart 6 54.9% (P < 0.0001) clinical response at week 6 17.9% (P < 0.0001) clinical remission at week 6 PURSUIT-M [7] 151 50 mg sc every 4 wk 54 47% (P = 0.010) clinical response at week 54 23.2% clinical remission at week 54 151 100 mg sc every 4 wk 54 49.7% (P < 0.001) clinical response at week 54 27.8% (P = 0.004) clinical remission at week 54…”

“…Up to 4 years of data for adalimumab-treated patients from ULTRA 1 and 2, and the open-label extension ULTRA 3 have been presented [18] . A total of 600/1094 patients enrolled in ULTRA 1 or 2 were randomized to receive adalimumab and induced in the intent to treat analyses.…”

“…Three events of B-cell lymphoma occurred during ULTRA 3. All three patients had a history of smoking and either previous or concomitant azathioprine use [18] .…”