Tofacitinib may be effective in AS through its direct inhibition of the JAK2/TYK2 signal transduction of IL12/23, or indirectly through inhibition of JAK1/JAK3 signal transduction of IL7. Both these cytokine pathways feed into Th17 activation, currently believed to be the main pathogenic mechanism in AS and Psoriatic Arthritis.
IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis
Tofacitinib is effective for both the skin and the joint pathologies in Psoriatic Arthritis. It performs better for the skin at the higher dose of 10mg twice a day. It is currently pending FDA approval for this indication.
Given its salutary effects on Psoriatic skin disease and mucosal lesions in Ulcerative Colitis, as well as earlier reports of efficacy in Vitiligo, Alopecia and Atopic Dermatitis, this report on efficacy in Dermatomyositis comes as no surprise.
Perhaps Cutaneous Lupus Erythematosus, Scleroderma and Crohn's Disease may be found eventually to respond to Tofacitinib as well.