piperidines and Sarcoidosis--Pulmonary

Topics: Administration, Oral; Aged; Biopsy; Female; Humans; Janus Kinases; Lung; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies; Sarcoidosis; Sarcoidosis, Pulmonary; Signal Transduction; Skin; Skin Diseases; STAT Transcription Factors; Tomography, X-Ray Computed; Treatment Outcome

This is a prospective, open-label, proof-of-concept study of tofacitinib, a Janus kinase inhibitor, as a steroid-sparing therapy in corticosteroid-dependent pulmonary sarcoidosis. Five patients with corticosteroid-dependent pulmonary sarcoidosis were treated with tofacitinib 5 mg twice daily. The primary endpoint was a ≥ 50% reduction in corticosteroids at week 16 with no worsening in pulmonary function or respiratory symptoms. 60% of patients (3/5) met the primary endpoint. One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis. The three patients who met the primary endpoint each tapered to ≤ 5 mg/day prednisone, respiratory symptoms improved, and spirometry remained stable. In this proof-of-concept study, the addition of a JAK-inhibitor allowed 60% of patients with pulmonary sarcoidosis to successfully taper corticosteroids. JAK-inhibitors are a promising therapy for pulmonary sarcoidosis, which require further investigation in randomized trials.Trial Registration clinicaltrials.gov NCT03793439; registered Jan 4, 2019.

Topics: Adult; Female; Glucocorticoids; Humans; Male; Middle Aged; Pilot Projects; Piperidines; Prednisone; Proof of Concept Study; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Sarcoidosis, Pulmonary; Spirometry; Treatment Outcome

Topics: Adrenal Cortex Hormones; Humans; Pharmaceutical Preparations; Piperidines; Prospective Studies; Pyrimidines; Sarcoidosis; Sarcoidosis, Pulmonary; Steroids

There is evidence that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling plays a role in the pathogenesis of sarcoidosis. We treated a patient with cutaneous sarcoidosis with the JAK inhibitor tofacitinib; the patient had not previously had a response to medications and had not received systemic glucocorticoids. This treatment resulted in clinical and histologic remission of her skin disease. Sequencing of RNA and immunohistochemical examination of skin-lesion samples obtained from the patient before and during therapy and immunohistochemical testing of lesion samples obtained from other patients with cutaneous sarcoidosis support a role for JAK-STAT signaling in cutaneous sarcoidosis. (Funded by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research and others.).

Topics: Female; Humans; Immunohistochemistry; Janus Kinases; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Remission Induction; Sarcoidosis; Sarcoidosis, Pulmonary; Sequence Analysis, RNA; Signal Transduction; Skin; Skin Diseases; STAT Transcription Factors