Janus kinase inhibitors for autoimmune disorders

Chaplin, Steve

doi:10.1002/psb.1635

Cited by 5 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JIA is a progressive autoimmune disease affecting children under the age of 16. While its mechanism of action is poorly understood, previous treatments have attempted to reduce inflammation by inhibiting TNF alpha and IL-6 [ 11 , 12 ]. However, these medications have been noted to be ineffective in many patients.…”

Section: Reviewmentioning

confidence: 99%

See 1 more Smart Citation

Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis

Jones,

Keller,

Abadie

et al. 2023

Cureus

View full text Add to dashboard Cite

Polyarticular course juvenile idiopathic arthritis (pcJIA) is a form of arthritis that affects at least five joints at a time and presents before the age of 16. Its most common symptoms are pain, swelling, redness, and a limited range of motion, making it incredibly difficult for patients diagnosed to function in daily life. Historically, the leading treatment options have consisted of non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. However, these drugs have serious toxic side effects associated with long-term use in addition to being ineffective in refractory cases. Recently, small molecule biologics have emerged as an alternate treatment to pcJIA. Tofacitinib is a small molecule JAK inhibitor that blocks the JAK/STAT cascade and decreases the transcription of genes responsible for immune function. We conducted a risk-benefit analysis to determine the viability of tofacitinib as a treatment for pcJIA. In our review, we found the side effect profile of tofacitinib to be relatively mild, with many of the serious adverse side effects occurring in those immunocompromised and those with impaired renal and hepatic metabolism. Overall, we have determined that tofacitinib has the potential to be effective in reducing flare-ups and lowering erythrocyte sedimentation rate (ESR) in immunocompetent patients with pcJIA. Additionally, our review has found that tofacitinib has the potential to be effective in patients who are refractory to traditional treatment. However, large-scale clinical trials are needed to determine if this effect holds true in younger pediatric populations, as limited data surrounds this demographic.

show abstract

Section: Reviewmentioning

confidence: 99%

“…The JAK pathway has only recently been understood. It consists of a family of receptor tyrosine kinases that are an integral part of the signaling of cytokines that bind to cytokine receptors type I and II [ 11 ]. When a cytokine binds to its receptor, it causes the receptor to dimerize.…”

Section: Reviewmentioning

confidence: 99%

Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis

Jones,

Keller,

Abadie

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…Neutropenia, anemia, and increased alanine aminotransferase have also been attributed to baricitinib administration 12 . Accordingly, baricitinib should not be initiated in patients with an absolute neutrophil count less than 1 × 109 cells/L, or absolute lymphocyte counts less than 0.5 × 109 cells/L 70 . This is of particular importance in COVID‐19 patients, as severe cases usually have lymphopenia and exhibit exhausted lymphocyte phenotypes 71 .…”

Section: Safetymentioning

confidence: 99%

“…12 Accordingly, baricitinib should not be initiated in patients with an absolute neutrophil count less than 1 × 109 cells/L, or absolute lymphocyte counts less than 0.5 × 109 cells/L. 70 This is of particular importance in COVID-19 patients, as severe cases usually have lymphopenia and exhibit exhausted lymphocyte phenotypes. 71 Moreover, liver enzyme dysregulation following baricitinib administration has frequently been observed in patients receiving concomitant hepatotoxic drugs such as MTX or isoniazid.…”

Section: Safetymentioning

confidence: 99%

Baricitinib: From Rheumatoid Arthritis to COVID‐19

Assadiasl

Fatahi

Mosharmovahed

et al. 2021

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Baricitinib is a JAK1/2 inhibitor first approved for treating moderate to severe rheumatoid arthritis but later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. There is a growing body of evidence, obtained from clinical trials and case reports, demonstrating clinical and paraclinical improvement in patients following administration of baricitinib including rheumatoid arthritis, systemic lupus erythematosus, psoriasis, atopic dermatitis, alopecia areata, interferon-mediated auto-inflammatory diseases, graft versus host disease, diabetic kidney disease, and recently, coronavirus disease-19. However, despite overall encouraging results, many adverse effects have been observed in baricitinib-treated patients ranging from simple infections to increased risk of malignancies, particularly in long-term use. The significant efficacy of baricitinib on one hand and the probable adverse effects, on the other hand, urge for further investigations before establishing it as a part of standard therapeutic protocols.Herein, we have provided a review of the studies which have used baricitinib for treating various inflammatory disorders and summarized the advantages and disadvantages of its administration.

show abstract

“…The JAK family is comprised of four members (JAK1, JAK2, JAK3, and TYK2). Selective inhibition of JAK1 has been hypothesized to have an improved risk-benefit in the treatment of RA. − Upadacitinib (Figure ) is a selective JAK1 inhibitor and has recently been approved to treat RA. − It is also under investigation for the treatment of other autoimmune diseases such as atopic dermatitis, ankylosing spondylitis, Crohn’s disease, and others.…”

Section: Introductionmentioning

confidence: 99%

Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib

Rozema

Bhagavatula

Christesen

et al. 2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

Process development of a six-stage synthesis of upadacitinib, a JAK1 inhibitor, is described. It is highlighted by an enantioselective and diastereoselective hydrogenation of a tetrasubstituted olefin to set the two pyrrolidine stereocenters. Preparation of the main fragments and strategies to link them together, optimization of the imidazole cyclization, and in-depth understanding of the formation of the urea moiety at the final stage are discussed.

show abstract

Janus kinase inhibitors for autoimmune disorders

Cited by 5 publications

References 20 publications

Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis

Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis

Baricitinib: From Rheumatoid Arthritis to COVID‐19

Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib

Contact Info

Product

Resources

About