Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study

Abstract

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. 5 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 One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis.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.

Treatment of cutaneous sarcoidosis with tofacitinib: A case report and review of evidence for Janus kinase inhibition in sarcoidosis

“…Nine studies used oral JAK inhibitors, including tofacitinib (JAK1/2/3), ruxolitinib (JAK1/2), and baricitinib (JAK1/2), and 2 studies used topical (compounded) 2% tofacitinib ointment. 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 Key details of these reports are summarized in Table I . Two of the 3 ruxolitinib reports, which were among the earlier reports, were based on observations made in patients taking the medication for coexisting polycythemia vera, with incidental improvement in sarcoidosis.…”

“… Δ Systemic? Disease duration Fitzpatrick type Sex Country Reference Oral JAK inhibiton Tofacitinib JAK1/2/3 5 mg twice daily 1 CR N/A 8 y II F United States Damsky et al 4 Tofacitinib JAK1/2/3 5 mg twice daily 3 CR (3) N/A 6-25 y VI 2 F, 1 M United States Damsky et al 5 Tofacitinib JAK1/2/3 5-10 mg twice daily 1 CR CR 21 y I F United States Damsky et al 6 Tofacitinib JAK1/2/3 2.5-16 mg daily 5 CR/NCR (3), PR (2) PR (3), N/A (2) Not reported White F Australia Kerkemeyer et al 8 Tofacitinib JAK1/2/3 5 mg twice daily 5 N/A PR (3), N/A (2) 1-5 y 4 Caucasian, 1 African American 4 M, 1 F United States Friedman et al 9 Ruxolitinib JAK1/2 5 mg twice daily 1 CR NCR 18 y European anscestry F France Rotenberg et al 10 Ruxolitinib JAK1/2 10 mg twice daily 1 CR PR 1 y ...…”

State-of-the-Art Treatments for Sarcoidosis

“…Among them, tofacitinib showed 60% steroid-sparing efficacy in chronic sarcoidosis in a small proof-of-concept study. 56 An overview of drugs used, dosages, and respective monitoring events, with a focus on CS, is presented in Table 2 .…”

LUNG Year in Review: 2021

“…The journal saw a number of submissions on the topic of sarcoidosis in 2021. The best of those contributions examined various aspects of the disease, including pharmacological therapy [ 65 , 66 ], assessment [ 67 ], and clinical characteristics [ 68 ].…”