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I don’t know JAK — but I will! Ruxolitinib improving chilblain lupus erythematosus

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By Warren R. Heymann, MD
May 31, 2016

The JAK inhibitors are among the current darlings of treating autoimmune diseases. Recent articles about  tofacitinib for vitiligo (1) and alopecia areata (2) have been reported in the lay press with considerable fanfare.

Ruxolitinib (Jakafi) is indicated for treating intermediate to high-risk myelofibrosis and polycythemia vera. Wenzel et al report the case of a 69 year-old woman with myelofibrosis and an associated autoinflammatory disorder manifested by fever, nephrotic syndrome, and acute liver failure. She had a positive ANA but all other autoantibodies were negative. After treatment with steroids, she was placed on ruxolitinib for a year. When the dose was reduced because of thrombocytopenia, she developed acral, red, scaly lesions of her fingers, toes, and ears. Because a drug eruption was suspected, the ruxolitinib was discontinued — her skin got worse. She was then referred to dermatology. A biopsy confirmed the diagnosis of lupus, clinically consistent with the chilblain type.  A decision was made to reintroduce the ruxolitinib at the full dose. She had a complete remission of her lesions within 4 months (3).

I have no personal experience prescribing either tofacitinib or ruxolitinib. Reading through the adverse reaction section of Epocrates, it seems as though we would follow the use of these agents in a similar manner to other biologics. Interestingly, progressive multifocal leukoencephalopathy is listed for Jakafi, but not Xeljans. I am not sure how anxious I am to prescribe these drugs (because of potential adverse reactions and cost) for either alopecia areata or vitiligo, however, I would certainly be less reluctant to do so for lupus, dermatomyositis, severe atopic dermatitis or psoriasis (for which either more standard therapies have failed or are contraindicated). What would be optimal, of course, is the further development of topical Janus Kinase inhibitors; they appear to be on the horizon. Please read the following abstract from the excellent article by Ghoreschi and Gadina, which surveys the emerging role of these fascinating drugs.

Cytokines are key mediators of the development and homeostasis of haematopoietic cells, critical for host defense, but also for the development of autoimmune and inflammatory diseases such as psoriasis or rheumatoid arthritis (RA). Blocking cytokines activity by interfering with the ligand-receptor association has been successfully employed to treat several immune disorders. A subgroup of cytokines signals through receptors requiring the association with a family of cytoplasmic protein tyrosine kinases known as Janus kinases (Jaks). Jaks have recently gained significant attention as therapeutic targets in inflammation and autoimmunity, and several Jak inhibitory small molecules have been developed. The first two Jak inhibitors, tofacitinib and ruxolitinib, have been approved for the treatment of RA and primary myelofibrosis, respectively. Efficacy and safety data suggest that some of these oral Jak inhibitors as well as their topical formulations may soon enter the daily clinical practice for treating patients with psoriasis, lupus erythematosus or other inflammatory skin diseases. While biologics typically target one single cytokine, these new immunomodulators can inhibit signals from multiple cytokines intra-cellularly and therefore could be useful when other therapies are ineffective. Thus, Jak inhibitors may replace some traditional immunosuppressive agents and help patients not responding to previous therapies.

1. Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: A pathogenesis-directed therapy. JAMA Dermatology 2015: 151: 1110-2.
2. Jabbari A, et al. Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers. Exp Dermatol 2016 April 27 [Epub ahead of print].
3. Wenzel J, et al. JAK 1/2 inhibitor ruxolitinib controls a case of chilblain lupus erythematosus. J Invest Dermatol 2016; 136: 1281-3.
4. Ghoreschi K, Gadina M. Jakpot! New small molecules in autoimmune and inflammatory diseases. Exp Dermatol 2014; 23: 7-11.

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