S0881 Therapeutic Drug Monitoring Dosing Regimen With Adalimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the SERENE-UC Maintenance Study
Bibliographic record
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".