Since the end of the last century, biological therapies have taken the rheumatoid arthritis (RA) pharmaceutical market by storm. Anti-TNFs were launched in the late 1990’s and have rapidly become worldwide brands. Within a decade, Humira was the highest earning product across the entire market.
The success of biologics was defined by their comparable high efficacy over traditional therapeutic agents. This was primarily driven by advances in specific target selectivity. Older treatments such as methotrexate and corticosteroids are comparatively blunt tools, with a myriad of effects across the immune system and dose limiting toxicity. Treatment with biologics has led to a seismic shift…
In an anecdotal survey of 21 MPN patients taking Jakafi for relief of MF symptoms, first results vary from highly positive to unacceptable.
Janus kinase (JAK)/signal transducers and activators of transcription (STATs) are a group of molecules associated with one of the major pathways through which many cytokines exert and integrate their function, and as such they are increasingly recognized as playing critical role in the pathogenesis subserving various immune-mediated diseases, including RA, PsA, SpAs, IBD, skin disorders (e.g. alopecia areata, atopic dermatitis), single-gene disorders like interferonopathies, and others.
Altered production of cytokines can result in pathologies ranging from autoimmune diseases to malignancies. The Janus Kinases family is a small group of receptor-associated signaling molecules that is essential to the signal cascade originating from type I and type II cytokine receptors.
In recent years a substantial battery of evidence has been collected indicating the potential role of Jakinibs to interact with the specific elements of the immune system, therefore changing the inflammatory response. JAK kinase blockade offers a unique opportunity to block most of the key cytokines enabling the deep interaction into immune system functioning.
“We now have a much better understanding of the immunological pathways involved in vitiligo, which is providing insight on how to target and treat the disease better,” an expert says.
Proof provided by biological therapies that cytokines are truly key drivers of immune-mediated diseases has spurred effort in targeting their associated signaling pathways. Small-molecule drugs that inhibit Janus kinases (jakinibs), which are essential signaling mediators downstream of many pro-inflammatory cytokines, have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies like rheumatoid arthritis, psoriasis and inflammatory bowel disease.
In one study, about half of people with RA who didn't improve with biologic drugs had symptoms that were less severe after they took the JAK inhibitor tofacitinib for 3 months.
Another advantage of JAK inhibitors is that you can take them by mouth.
The treatment of rheumatoid arthritis has changed dramatically over the last two decades since the development of biological disease-modifying anti-rheumatic drugs (bDMARDs). Moreover, Janus kinase (JAK) inhibitors became available in 2013. JAK inhibitors are low-molecular-weight compounds, which exert anti-rheumatic effects by suppressing the action of JAK, an intracellular tyrosine kinase.
The critical function of Jaks in cytokine signaling has made them targets for industry to consider. At present there are a number of such inhibitors in clinical use or being tested in clinical trials.
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... considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals.
JAK inhibitors have promising therapeutic potential in COVID-19 with dual anti-inflammatory and anti-viral effects. Vigilance to the potentially increased thrombotic risk associated with JAKi is recommended, given the hypercoagulability of COVID-19.
The past decade has witnessed an explosion in trial data on JAK inhibitors (JAKi). These small molecules target the Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway, blocking crucial cytokines across a septum of rheumatic diseases.
For the treatment of intermediate and high risk myelofibrosis.
For the treatment of acute graft-versus-host (GVHD) not responsive steroids, in adults and pediatric patients 12 years of older.