Janus kinase inhibitors

introduction

the Janus kinase family of enzymes are associated with cell surface cytokine receptors and are part of the Signal Transducer and Activation of Transcription (JAK-STAT) pathway
in 2005, an acquired mutation of the Janus kinase 2 gene (V617F mutation) was discovered in >95% of patients with polycythaemia rubra vera and in ~50% of those with essential thrombocytosis or primary myelofibrosis
- this mutation makes Janus kinase continuously active resulting in thrombocytosis and leukocytosis (high WCC) independently from growth factor regulation.
JK inhibitors can be expected to impact immune responses and may increase risk of infections, shingles, etc.
JK inhibitors appear to have a 3.8x higher odds of causing acne ¹⁾
other adverse effects of JK inhibitors:
- infections such as nasopharyngitis, URTI's, UTIs
- reactivation of herpes simplex or shingles
- nausea, diarrhoea
- elevated AST, ALT, bilirubin
- hypercholesterolaemia, hypertriglyceridaemia
- decreased Hb, neutropenia
- rarely, thromboembolic events, non-melanoma skin cancers, solid cancers

marketed in Aust from 2013 as Jakavi
selective inhibitor of Janus kinase 1 and 2
appears to reduce spleen size or prevent it enlarging further
50% reduction in disease associated symptoms compared with 5% for placebo, but these return to baseline within 1 week of stopping Rx, and serious withdrawal symptoms make gradual dose reduction a recommendation.
BUT 82% developed anaemia, 67% thrombocytopenia and 15% neutropenia hence need to monitor FBE
and it does not seem to prevent leukaemic transformation
may have a role in reducing neutrophil activation is severe infections such as COVID-19 coronavirus (2019-nCoV / SARS-CoV-2) which may otherwise increase risk of thrombosis ²⁾
dose 15-25mg bd

non-selective inhibitor of Janus kinase 1, 2 and 3, although preferential inhibition of 3 and 1 over 2.
approved for used in Rx of rheumatoid arthritis in 2015 in Aust.

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