Ophthalmology Science (Jan 2025)

Systemic Treatment with the Janus Kinase Inhibitor Baricitinib in Ocular Chronic Graft-versus-Host Disease

  • Taylor McManus, BS, MS,
  • Noa G. Holtzman, MD,
  • Aaron Zhao, BS,
  • Chantal Cousineau-Krieger, MD,
  • Susan Vitale, PhD, MHS,
  • Edmond J. FitzGibbon, MD,
  • Debbie Payne, BS, MBA,
  • Janine Newgen, COT,
  • Celestina Igbinosun, BSN, RN,
  • Annie P. Im, MD,
  • Cody Peer, MS, PhD,
  • William Douglas Figg, Sr., Pharm D,
  • Edward W. Cowen, MD,
  • Jacqueline W. Mays, DDS, PhD,
  • Steven Pavletic, MD, PhD,
  • M.Teresa Magone, MD

Journal volume & issue
Vol. 5, no. 1
p. 100627

Abstract

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Objective: To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD). Design: Prospective phase 1 to 2 single institution trial. Subjects: Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD. Methods: Oral baricitinib (2 mg and 4 mg) was administered daily for up to 12 months in an intrapatient dose-escalation design. National Institutes of Health (NIH) oGVHD score, vision, corneal Oxford staining (COS), tear break-up time (TBUT), Schirmer I test (ST) without anesthesia, and microliter tear equivalent conversion were assessed at baseline, 6 months (primary efficacy end point), and 12 months if patients remained on the drug. Main Outcome Measures: Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months. Results: At 6 months, the NIH oGVHD score significantly improved (P = 0.014) with all OSD parameters also showing improvement, though not statistically significant. COS baseline, 2.17 to 0.95; TBUT baseline, 6.66 to 8.18 seconds, Schirmer I baseline, 3.86 mm (2.6 μl) to 5.56 mm (3.9 μl). For patients continuing treatment at 12 months improvements persisted compared with the baseline but remained statistically nonsignificant. Corneal Oxford staining decreased to 0.94; TBUT increased to 8.95 seconds, and ST improved to 10.19 mm (7.2 μL). Conjunctival fibrosis was present in 39% (n = 7) of the patients at baseline. The greatest improvement was observed in the 11 patients without prior conjunctival fibrosis compared with the baseline: COS 1.84, TBUT 6.32 seconds, ST 4.07 mm (2.1 μl); 6 months: COS 0.25 (P = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 μl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 μl). Vision was stable in all groups. Two patients developed asymptomatic, self-limited conjunctival papillomas, and 1 patient developed uncomplicated bacterial conjunctivitis twice. No dose limiting toxicity was observed. Severe adverse events with hospitalizations for possible drug-related systemic infections occurred in 5 patients. Conclusions: Systemic baricitinib was well-tolerated, improved NIH oGVHD scores and OSD parameters in patients with oGVHD, with the greatest benefits observed in patients without pre-existing conjunctival fibrosis. Conjunctival fibrosis may affect outcomes and should be considered in patient selection for clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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