Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare

Abstract Background Sarcoidosis and granuloma annulare (GA) are cutaneous granulomatous disorders that can be difficult to treat. There is evidence of underlying JAK-STAT pathway activation in sarcoidosis, suggesting JAK inhibition might be effective. Objective To evaluate treatment with tofacitinib, a JAK inhibitor, in patients with recalcitrant sarcoidosis and GA Methods A prospective evaluation of tofacitinib in four consecutive patients with recalcitrant cutaneous sarcoidosis (n=3) and generalized GA (n=1) was conducted. Immunohistochemical analysis of skin biopsies from other patients with sarcoidosis (n=21) and GA (n=17) was performed to characterize patterns of JAK-STAT pathway activation. Results Tofacitinib resulted in a mean [SD] improvement in the baseline CSAMI and GASI scores of 96% [2%]. Histologic resolution of disease was documented in all patients (3 out of 3) who underwent skin biopsies on therapy. Constitutive STAT1 and STAT3 activation was observed in both sarcoidosis and GA, albeit in different patterns. SIRPα may explain differences in JAK-STAT signaling between sarcoidosis and GA. Limitations The study is limited by the small number of subjects. Conclusions Tofacitinib resulted in dramatic improvement in four patients with cutaneous sarcoidosis and GA. Larger studies are underway to better understand this effect.