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

To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD).

Prospective phase 1 to 2 single institution trial.

Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD.

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.

Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months.

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 microl) to 5.56 mm (3.9 microl). 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 microL). 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 microl); 6 months: COS 0.25 (P = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 microl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 microl). 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.

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.

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