Selective JAK1 inhibition using upadacitinib for the management of inflammatory bowel diseases
Bibliographic record
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal tract, with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The cause of IBD is not fully understood, but it involves a complex interaction between genetics and environmental factors that trigger an abnormal immune response in the gut. The immune system plays a central role in IBD, with an imbalance between pro- and anti-inflammatory mediators leading to an exaggerated immune response and infiltration of immune cells into the mucosa.2 This infiltration triggers the release of cytokines, interleukins and interferons, activating signalling pathways that damage the mucosal barrier. Despite the presence of several treatment choices for individuals with inflammatory bowel diseases (IBDs), there still remain significant challenges. The symptoms associated with the disease have a detrimental impact on individuals’ quality of life, and uncontrolled inflammation can lead to complications of disease requiring surgery, further emphasizing the need for improved treatment to achieve disease control and enhance overall well-being. The involvement of the Janus kinase inhibitor (JAK) family of enzymes in the signalling pathways of several pro-inflammatory cytokines plays an important role in the pathogenesis of IBD, which makes it a potential therapeutic target. Tofacitinib, a nonselective pan-JAK inhibitor, was the first JAK inhibitor treatment approved for moderate-to-severe cases of UC. However, long-term studies on rheumatoid arthritis (RA) patients treated with tofacitinib have highlighted safety concerns including potentially higher risk of major adverse cardiovascular (CV) events and venous thromboembolism. The second generation of JAK inhibitors include selective JAK1 therapies, such as upadacitinib. Upadacitinib is a selective and reversible JAK inhibitor approved for treating UC; RA; psoriatic arthritis; ankylosing spondylitis (AS); and atopic dermatitis, and approval for Crohn’s disease is expected in the near future. This review intends to describe the mechanism of upadacitinib, evaluate the current clinical evidence of its effectiveness in treating IBD, and discuss safety considerations.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".