Open-Label Pilot Study of Interferon Gamma–1b in Patients With Non-Infantile Osteopetrosis

Andrew Nguyen, Weston P Miller, Ashish O Gupta, Troy C Lund, Daniel Schiferl, Lok Sze Kelvin Lam, Zorayr Arzumanyan, Paul J. Orchard, Lynda E. Polgreen

Research output: Contribution to journalArticlepeer-review

Abstract

The only treatment currently available for patients with severe infantile osteopetrosis is hematopoietic cell transplantation (HCT). HCT-related toxicity and mortality risks typically preclude its use in non-infantile patients, and other therapies are needed for these patients who have significant disease-related morbidity. Interferon gamma-1b is currently approved by the U.S. Food and Drug Administration (FDA) for treatment of severe infantile osteopetrosis (autosomal recessive osteopetrosis [ARO]). However, little is known about the effects of interferon gamma-1b in non-infantile osteopetrosis. Thus, this pilot study aimed at testing the safety and tolerability of interferon gamma-1b in patients with non-infantile osteopetrosis and assessing the clinical effects. We performed a 12-month, open-label, multi-center pilot study involving patients >1 year-old diagnosed radiographically with osteopetrosis. Patients were initiated on interferon gamma-1b subcutaneously 15 μg/m 2 three times weekly, to be titrated over 3 weeks to a goal of 100 μg/m 2 three times weekly. The primary aim was safety and tolerability. The secondary aims were to assess changes in peripheral quantitative computed tomography (pQCT), dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) Z-scores, bone biomarkers, and quality-of-life (QOL) measures. Four of the five participants enrolled withdrew from the study between 3 and 9 months due to intolerability of interferon gamma-1b-related flu-like symptoms. The last participant completed the study with the addition of prednisone on days of interferon gamma-1b administration. DXA and pQCT outcomes were stable over 6-12 months, and there were no clear trends in bone biomarkers or QOL measures. No serious drug-related adverse events were reported during this study. Interferon gamma-1b was only tolerable in one of five participants with the addition of prednisone. The stabilization of BMD and other measures of bone health during this study suggest possible positive effects of interferon gamma-1b on osteopetrosis; however, additional data are needed before conclusions on treatment efficacy can be made. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Original languageEnglish (US)
Article numbere10597
JournalJBMR Plus
Volume6
Issue number3
DOIs
StatePublished - Mar 2022

Bibliographical note

Funding Information:
This study was funded by a grant from Horizon Pharmaceuticals to LEP. We acknowledge the TransGenomics Laboratory including Kevin Sandow for performing the biomarker assays.

Publisher Copyright:
© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Keywords

  • ANALYSIS/QUANTITATION OF BONE
  • BONE QCT/μCT
  • DISEASES AND DISORDERS OF/RELATED TO BONE
  • OSTEOPETROSIS
  • THERAPEUTICS

PubMed: MeSH publication types

  • Journal Article

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