Impact of Adalimumab therapy after 12 Weeks in patients with Crohnʼs Disease who were nonresponders at week 4
Bibliographic record
Abstract
Adalimumab, a fully human antibody targeting tumor necrosis factor, is approved for treatment of adults with moderate to severe Crohn's disease (CD). In clinical trials, 52-58% of patients responded to adalimumab by Week 41,2; however, some patients require additional time to respond. Additional data on the length of an adequate trial of adalimumab may benefit physicians when making treatment decisions. This analysis assessed the efficacy of adalimumab by Week 12 among patients who did not respond after 4 weeks using data from 2 clinical trials: the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM) and the open-label extension (OLE) of the Gauging Adalimumab Efficacy in Infliximab Nonresponders (GAIN) study. In CHARM, following a 4-week induction period in which all patients received OL adalimumab 80 mg/40 mg at Weeks 0/2, patients were randomized to placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly. In GAIN, patients who failed infliximab were randomized to adalimumab 160 mg/80 mg or placebo induction at Weeks 0/2. After 4 weeks, patients could enroll in an OLE study in which they received adalimumab 40 mg eow. Remission (CD Activity Index [CDAI] <150) and clinical response (CR-70; defined as a decrease from baseline CDAI of greater than or equal to 70 points) rates by Week 12 were evaluated for CHARM patients who were randomized to blinded adalimumab 40 mg eow and did not achieve a CR-70 response at Week 4 and GAIN patients who received OL adalimumab 40 mg eow after being randomized to the blinded adalimumab 160-/80-mg induction dose and did not achieve a CR-70 response at Week 4. In CHARM, 260 patients were initially randomized to blinded adalimumab 40 mg eow. Among 88 patients who did not respond (CR-70) at Week 4, 60% achieved CR-70 and 28% achieved remission by Week 12. By Week 12, 82% and 57% of patients who were randomized to eow therapy (including Week-4 responders and nonresponders) achieved CR-70 and remission, respectively. In GAIN, 159 patients were initially randomized to adalimumab 160 mg/80 mg; 150 with nonmissing CDAI entered the OLE. Among 69 patients who did not respond (CR-70) at Week 4, 67% receiving OL adalimumab 40 mg eow achieved CR-70 and 25% achieved remission by Week 12. Combining responders and nonresponders (n = 150), most patients achieved CR-70 response (85%) and remission (45%) by Week 12. Most initial Week-4 nonresponders benefited from continued treatment with adalimumab 40 mg eow through Week 12, with almost two-thirds achieving CR-70 response and more than one-fourth achieving remission. When continuing adalimumab therapy for up to 12 weeks, incremental benefits in clinical response were demonstrated in patients not responding to initial induction dosing.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".