S0648 Clinically Adjusted vs Therapeutic Drug Monitoring Dosing Regimens With Adalimumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the SERENE-CD Maintenance Study
Bibliographic record
Abstract
INTRODUCTION: Adalimumab (ADA) is well-tolerated and effective in patients (pts) with Crohn's disease (CD).1,2 The Serene-CD phase 3 study evaluated higher vs standard dosing regimens of ADA 12-week (Wk) induction and 44Wk maintenance therapy in adults with moderate to severe CD. Outcomes of ADA maintenance therapy using clinically adjusted (CA) dosing or therapeutic drug monitoring (TDM) were explored. METHODS: Safety and efficacy of CA and TDM maintenance regimens at Wk56 were assessed. Clinical responders (N = 184) completing Induction were re-randomized at Wk12 and assigned 1:1 to CA or TDM, both arms initially receiving 40 mg ADA every other wk (EOW). The CA arm could escalate to every wk (EW) based on CDAI (≥220) or high-sensitivity C reactive protein (hs-CRP, ≥10 mg/L). The TDM arm could escalate to EW at Wks 14, 28, or 42 if ADA serum concentration was < 5 µg/mL or 5–10 µg/mL with CDAI≥220 or hs-CRP≥10 mg/L. Once escalated, the pt remained at 40 mg EW. Key exploratory efficacy endpoints at Wk56 included clinical remission and endoscopic response and remission (Table 1). Safety was analyzed in pts receiving at least 1 dose of maintenance study drug. RESULTS: Of re-randomized pts, 76 (82.6%) CA and 79 (85.9%) TDM completed the study. BL characteristics/demographics were well-balanced between treatment arms. In CA and TDM arms, 26 (28.2%) and 36 (39.1%) pts escalated to EW dosing, respectively, with most in both groups escalating at Wk14 (13/26 CA, 21/36 TDM). No difference in proportion of pts achieving Wk56 clinical remission, steroid-free clinical remission among subjects taking corticosteroid at Induction BL, endoscopic response, endoscopic remission, or deep remission between CA vs TDM (Table 1) was found. No significant differences observed between the two groups for sustained clinical remission among Wk12 clinical remitters, or for maintenance of endoscopic response and remission among Wk12 responders and remitters respectively (Table 1). Dose escalation was driven by hs-CRP in CA arm and by serum drug levels in TDM arm. Observed safety profile was similar between groups; no new safety signals or unexpected trends were identified. CONCLUSION: Key efficacy endpoints indicate both CA and TDM maintenance regimens are similar as observed in the SERENE-CD maintenance study. Both dosing regimens were well-tolerated with a similar safety profile.3 TDM used for dose adjustment showed no clinical benefit over use of clinical symptoms and biomarkers alone.Table 1
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".