Ruxolitinib, an oral JAK1 and JAK2 inhibitor, in myelofibrosis
Bibliographic record
Abstract
INTRODUCTION: Myelofibrosis (MF) is a debilitating hematologic malignancy characterized by progressive splenomegaly, burdensome symptoms, cytopenias and shortened survival. Chronic alterations in Janus-associated kinase-signal transducer and activator of transcription (JAK-STAT) signaling have been identified in the pathogenesis of MF, making this pathway a target for drug development. Ruxolitinib is the first JAK1 and JAK2 inhibitor to be approved by the US Food and Drug Administration. AREAS COVERED: This review describes the characteristics of MF, the current therapeutic options and need for effective therapies, the contribution of aberrant JAK-STAT signaling to various disease-specific manifestations and the pharmacodynamics, pharmacokinetics, efficacy and tolerability of ruxolitinib. Articles describing MF disease burden and results of ruxolitinib pre-clinical and clinical trials were identified and summarized. EXPERT OPINION: Conventional MF treatments alleviate some MF symptoms but have limited efficacy, do not modify the natural history of the disease and are not approved for MF. The JAK1 and JAK2 inhibitor ruxolitinib has shown promising results in pre-clinical and clinical trials. In Phase III trials, ruxolitinib was shown to reduce splenomegaly and improve MF-related symptoms. Recent evidence also suggests that ruxolitinib may improve survival. The most common adverse events were anemia and thrombocytopenia, which were managed with dose adjustments (or red blood cell transfusions for anemia).
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".