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 One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis.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

Keywords: Janus kinase inhibitors; Pulmonary sarcoidosis; Sarcoidosis.

Conflict of interest statement

Conflicts of interest/Competing interests: JTR consults for Gilead, Abbvie, UCB, Roche, Santen, Corvus, Celldex, Affibody, Keyverna, Horizon, and Novartis.

Figures

Figure 1:. Flowchart of patient recruitment and dropout.

5 patients were screened and enrolled in the study. One was lost to follow up at week 4 due to an unexpected move out of state; this patient was lost to follow up prior to steroid taper. 4 patients tapered prednisone and were included in the final analysis. *5 subjects included in assessment of adverse events

Figure 2:. Clinical data.

Prednisone taper is shown for all five patients; the remainder of clinical data includes only the four patients who attempted prednisone taper. A. Prednisone was tapered according to a specified protocol, Patient 2 was lost to follow up at week 4, and Patient 5 experienced worsening neurologic sarcoidosis requiring increased prednisone and ultimately withdrawal from the study. 3 patients met the primary endpoint and tapered to ≤5 mg/day. All three tapered off prednisone during the 1-year extension; 2 completed the 1-year extension and Patient 4’s extension study is ongoing. B. Pulmonary function was stable for all patients given established 10% between-test margin of variability for spirometry measurement. *DCLO is only shown for 3 patients, as this was done at baseline and week 16. C. Saint George Respiratory Questionnaire (SGRQ) scores all improved during the trial; a clinically significant difference for SGRQ is 4 units, thus all SGRQ changes were clinically significant. D) Chest radiographs from two patients whose radiographic findings improved during the study; patient 1 had a repeat chest x-ray at week 51 (during extension) showing further improvement. FEV1: forced expiratory volume in 1 second, FVC: forced vital capacity, DLCO: diffusion capacity for carbon monoxide.