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

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 One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis.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

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Acknowledgements

We wish to acknowledge the OHSU Massively Parallel Sequencing Shared Resource and the Gene Profiling Shared Resource, which performed all RNA extraction and sequencing for this work; Manny Rodriguez who assisted with the laboratory sample processing; and Puthyda Keath who assisted with patient coordination for this study. We additionally wish to thank the patients who participated in this study.

Funding

This is an investigator-initiated study with expenses paid by Pfizer. The pharmaceutical company played no role in the interpretation of data or the writing of this report. Funding also including NIH grants RO1 EY020249, RO1 EY026572, P30 EY010572, KL2TR002370, and 3T32HL094294-08S1. Funding was also provided by an unrestricted grant from Research to Prevent Blindness, the Grandmaison Fund for Autoimmunity Research, the William and Mary Bauman Foundation, the Stan and Madelle Rosenfeld Family Trust, and the OHSU Wheels Up Program.

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Authors and Affiliations

  1. Department of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. Mail Code OP09, Portland, OR, 97239, USA

    Marcia A. Friedman, Brian Le, Julianna Desmarais, Daniel Seifer, Dongseok Choi & James T. Rosenbaum

  2. Division of Pulmonary and Critical Care Medicine, Tuality Healthcare, Hillsboro, OR, 97123, USA

    Janelle Stevens

  3. Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA

    Kimberly Ogle, Dongseok Choi & James T. Rosenbaum

  4. OHSU-PSU School of Public Health, Oregon Health & Science University, Portland, OR, 97239, USA

    Dongseok Choi

  5. Graduate School of Dentistry, Kyung Hee University, Seoul, South Korea

    Dongseok Choi

  6. Integrated Genomics Laboratory, Oregon Heath & Science University, Portland, OR, 97239, USA

    Christina A. Harrington

  7. Department of Pulmonary Critical Care, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Peter Jackson

  8. Devers Eye Institute, Legacy Health Systems, Portland, OR, 97210, USA

    James T. Rosenbaum

Authors
  1. Marcia A. Friedman
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  2. Brian Le
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  3. Janelle Stevens
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  5. Daniel Seifer
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  6. Kimberly Ogle
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  7. Dongseok Choi
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  8. Christina A. Harrington
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  9. Peter Jackson
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  10. James T. Rosenbaum
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Contributions

JTR conceived of the study. JTR, MAF, JS, KO, and PJ designed the study. MAF, BL, KO, JD, DS, and JTR collected the clinical data. JTR, MAF, JS, PJ, MAF, BL, JD, and DS analyzed the clinical data. CH extracted RNA and performed RNA sequencing. DC analyzed transcriptomic data. MAF and BL wrote the first draft of the manuscript. All authors substantially contributed to this work, all authors critically revised this manuscript for important intellectual contact, all authors approve the version to be publish, and all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated.

Corresponding author

Correspondence to Marcia A. Friedman.

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Conflict of interest

JTR consults for Gilead, Abbvie, UCB, Roche, Santen, Corvus, Celldex, Affibody, Keyverna, Horizon, and Novartis.

Ethical Approval

This study was approved by the Oregon Health & Science University institutional review board (IRB 00017902) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Consent for Publication

Participants provided informed consent for publication of this study.

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Friedman, M.A., Le, B., Stevens, J. et al. Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study. Lung 199, 147–153 (2021). https://doi.org/10.1007/s00408-021-00436-8

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  • DOI: https://doi.org/10.1007/s00408-021-00436-8

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