Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies
Bibliographic record
Abstract
BACKGROUND: Evolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group. METHODS: This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated. RESULTS: Overall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected. CONCLUSIONS: Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".