S0881 Therapeutic Drug Monitoring Dosing Regimen With Adalimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the SERENE-UC Maintenance Study

Abstract

INTRODUCTION: Adalimumab(ADA) is efficacious and well tolerated in adults with ulcerative colitis(UC).1,2 SERENE-UC evaluated higher ADA dosing regimens for induction and maintenance in UC. Results of fixed-dosed maintenance arms were previously reported.3,4 We report outcomes of adjusting ADA dosing based on proactive monitoring of ADA serum levels and symptoms in the therapeutic drug monitoring(TDM) exploratory maintenance arm. METHODS: SERENE-UC was a Phase 3 study in adults with moderately to severely active UC. Following completion of induction study at Week (Wk) 8, all patients (pts) were re-randomized 2:2:1 to 44 wks of maintenance therapy with either ADA 40 mg every week (40EW), every other week (40EOW), or exploratory TDM regimens. Pts were stratified by induction regimen, clinical response status and clinical remission (CRem) status at Wk8 among Wk8 responders. All pts in TDM arm received ADA 40 mg at Wk8 and Wk10. Pts meeting dose-adjustment criteria(Rectal Bleeding Subscore ≥1 and/or ADA serum concentration < 10 μg/mL) as measured at prior study visit, could escalate to 40EW followed by a single dose of 160 mg. Mayo score(endoscopic component) was scored via central reading. TDM regimen was exploratory, and only descriptive statistics were provided. Safety was also assessed. RESULTS: Overall, 757/852 pts completed induction and were re-randomized at Wk8; 151 pts were in TDM arm. At Wk52, 36.5% (n = 27/74) of Wk8 responders in TDM arm achieved CRem, while 23.2% (35/151) of all pts and 10.4% (8/77) of Wk8 non-responders receiving TDM were in CRem. Proportion of Wk8 responders completing Wk52 escalating to TDM 40EW increased over time (Table); at Wk52, 83.6% (46/55) of pts received 40EW. Mean(SD) serum drug levels at Wk52 for the TDM 40EW, TDM 40EOW, and TDM 160 mg to 40EW regimens were 19.0(8.2) μg/mL, 13.9(4.0) μg/mL, and 10.3(7.8) μg/mL, respectively. Of the 71 pts who had dose escalation, 65% (46/71) were driven solely by an ADA serum concentration of < 10 μg/mL (Table). Safety profile of TDM arm was consistent with EW and EOW maintenance arms4; rates of treatment-emergent infections and serious infections were 33.8% and 2.0%, respectively. CONCLUSION: The SERENE-UC TDM 44 wk maintenance exploratory arm showed majority of patients escalated ADA to 40 EW, driven mainly by ADA serum levels. No new long-term safety concerns observed in TDM maintenance arm. Observed safety profile was comparable with known EOW maintenance safety profile.4Table 1