PYRAMID Registry: Long-term Safety and Effectiveness of Adalimumab by Baseline Immunomodulator Use in Patients With Crohnʼs Disease
Bibliographic record
Abstract
Introduction: A recent post hoc analysis of adalimumab (ADA) clinical trials in patients (pts) with Crohn's disease (CD) demonstrated no higher benefit in clinical efficacy up to Week 52 of ADA monotherapy (mono) compared to ADA combination (combo) therapy with immunomodulators (IMM)1. Long-term safety and effectiveness of ADA mono vs combo therapy is reported using data from the global post-marketing observational registry, PYRAMID. Methods: Pts newly prescribed or receiving ADA according to local product label were followed for ≥6 yrs in PYRAMID. In this analysis, remission (HBI < 5) was assessed at each visit in pts stratified by baseline ([BL], registry enrolment) IMM use (azathioprine, mercaptopurine, or methotrexate). Data are reported as observed. Incidence and rates (events [E]/100 patient-years [PY]) of registry treatment-emergent (TE) adverse events (AEs) are reported by BL IMM use. Results: At BL, 3227/5025 pts (64.2%) were receiving ADA mono (58.1% female; median age, 36.0 yrs; median CD duration, 8.4 yrs) and 1798/5025 pts (35.8%) were receiving ADA+IMM (55.3% female; median age, 35.0 yrs; median CD duration, 8.8 yrs). Mean±SD duration of ADA exposure during the registry was similar for ADA mono (1179.6±837.8 days) and combo groups (1271.4±828.0 days). BL mean±SD HBI was 5.6±5.0 and 5.8±5.0 for ADA mono or combo, respectively). One year after enrolment, approximately 70% of pts in ADA mono and combo groups achieved remission, with similar rates sustained over time during PYRAMID in the subgroups (Table 1). Rates of registry TEAEs were similar between the subgroups (Table 2). Numerically higher proportion of pts with ≥1 event of any AE, serious infections, AEs leading to discontinuation, and significantly more pts with ≥1 serious AEs were seen for combo vs mono groups (Table 2). Malignancy rates were 0.7 E/100 PY (n[%] = 62[1.9]) in the ADA mono group and 1.0 E/100 PY (n[%] = 54[3.0]) in the combo group. Non-melanoma skin cancer incidence rates were significantly higher in the combo group. Rates of lymphoma were similar between the subgroups (Table 2).Table: Table. Long-term effectiveness of adalimumab (ADA) by immunomodulator (IMM) use at baseline (as observed analysis)Table: Table. Overview of Registry Treatment-Emergent Adverse Events (TEAEs) by Immunomodulator (IMM) use at BaselineConclusion: Long-term effectiveness of ADA in pts with moderately to severely active CD enrolled in PYRAMID was similar for those treated with ADA mono or combo therapy at registry entry. Exposureadjusted malignancy rates tended to be higher in pts treated with ADA combo therapy. 1. Colombel J-F, et al. Aliment Pharmacol Ther 2017;45:50-62.
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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 | 0.006 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".