Selective JAK inhibitors in development for rheumatoid arthritis

@article{Norman2014SelectiveJI,
  title={Selective JAK inhibitors in development for rheumatoid arthritis},
  author={Peter Dr. Norman},
  journal={Expert Opinion on Investigational Drugs},
  year={2014},
  volume={23},
  pages={1067 - 1077}
}
  • P. Norman
  • Published 11 July 2014
  • Biology, Medicine
  • Expert Opinion on Investigational Drugs
Introduction: The JAK kinases are a family of four tyrosine receptor kinases that play a pivotal role in cytokine receptor signalling pathways via their interaction with signal transducers and activators of transcription proteins. Selective inhibitors of JAK kinases are viewed as of considerable potential as disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis. Areas covered: This article provides a review of the clinical development and available clinical results… 
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A narrative review focuses on the clinical efficacy and safety of baricitinib, but also provides an overview of its mechanism of action in relation to JAK1/JAK2 signalling and discusses the possible clinical implications in patients with RA.
Janus kinase inhibitors for the treatment of inflammatory bowel diseases: developments from phase I and phase II clinical trials
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An overview of the JAK inhibitors currently under investigation in phase I and II clinical trials for patients with Crohn’s disease and ulcerative colitis and the possible future perspectives for the treatment of IBD patients with this class of drugs are provided.
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TLDR
Although there are still issues in terms of their efficacy and safety currently, JAK inhibitors are expected to benefit more PsA patients in future.
JAK3-selective inhibitor peficitinib for the treatment of rheumatoid arthritis
TLDR
It is thought that more cautious consideration and measurement for adverse events are needed, after considering the safety results of ongoing clinical studies of peficitinib, which is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate.
JAK Inhibitors for Rheumatoid Arthritis
TLDR
Tofacitinib has been carefully evaluated in multiple phase 3 clinical trials, and although safety concerns cannot fully be answered until the drug is studied over longer periods of time, the data to date suggest that this drug—and perhaps other JAK inhibitors—may represent an important addition to the therapeutic armamentarium.
JAK-STAT inhibitors for the treatment of immunomediated diseases
Progress toward JAK1-selective inhibitors.
TLDR
The state-of-the-art research that evokes JAK1 selective inhibition is discussed, which shows a critical and potentially dominant role in the transduction of γc cytokine and in IL-6 signaling.
JAK inhibitors impair GM-CSF-mediated signaling in innate immune cells
TLDR
It is concluded that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells, and although baricitinib and upadacitinib almost completely blocked GM- CSF- mediated Jak2/ STAT5 signaling, the inhibitory effects of tofacitinIB were weaker at lower concentrations suggesting that variation exists among these JAKs in the inhibition of JAK 2 signaling pathways.
Comparative Efficacy of JAK Inhibitors for Moderate-To-Severe Rheumatoid Arthritis: A Network Meta-Analysis
TLDR
The NMA found that upadacitinib 15 mg once daily had numerically higher efficacy in terms of ACR response and clinical remission among approved JAK combination therapies and monotherapies for csDMARD-IR patients with RA.
Erratum to: JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects
TLDR
The JAK–STAT pathway is described, its role in autoimmunity is outlined, and the rationale/pre-clinical evidence for targeting JAK-STAT signaling is explained, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation JakinIBs.
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