McManus Taylor, Holtzman Noa G, Zhao Aaron, Cousineau-Krieger Chantal, Vitale Susan, FitzGibbon Edmond J, Payne Debbie, Newgen Janine, Igbinosun Celestina, Im Annie P, Peer Cody, Figg William Douglas, Cowen Edward W, Mays Jacqueline W, Pavletic Steven, Magone M Teresa
Ophthalmology Consult Services Section, National Eye Institute, NIH, Bethesda, Maryland.
National Cancer Institute, NIH, Bethesda, Maryland.
Ophthalmol Sci. 2024 Sep 30;5(1):100627. doi: 10.1016/j.xops.2024.100627. eCollection 2025 Jan-Feb.
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 ( = 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 ( = 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.
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.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
研究口服巴瑞替尼对慢性移植物抗宿主病（cGVHD）患者眼表疾病（OSD）的影响。
前瞻性1至2期单机构试验。
18例患有眼部移植物抗宿主病（oGVHD）且系统性类固醇难治性cGVHD的患者。
采用患者内剂量递增设计，每日口服巴瑞替尼（2毫克和4毫克），持续12个月。在基线、6个月（主要疗效终点）以及如果患者继续用药则在12个月时评估美国国立卫生研究院（NIH）oGVHD评分、视力、角膜牛津染色（COS）、泪膜破裂时间（TBUT）、无麻醉下的Schirmer I试验（ST）以及微升泪液当量换算。
6个月时有无结膜纤维化患者的NIH oGVHD评分、COS、TBUT和ST结果的改善情况。
6个月时，NIH oGVHD评分显著改善（P = 0.014），所有OSD参数也显示出改善，尽管无统计学意义。COS基线为2.17至0.95；TBUT基线为6.66至8.18秒，Schirmer I基线为3.86毫米（2.6微升）至5.56毫米（3.9微升）。对于在12个月时继续治疗的患者，与基线相比改善持续存在，但仍无统计学意义。角膜牛津染色降至0.94；TBUT增至8.95秒，ST改善至10.19毫米（7.2微升）。基线时39%（n = 7）的患者存在结膜纤维化。与基线相比，在11例无既往结膜纤维化的患者中观察到最大改善：COS 1.84，TBUT 6.32秒，ST 4.07毫米（2.1微升）；6个月时：COS 0.25（P = 0.018），TBUT 8.62秒，ST 9.12毫米（5.4微升）；12个月时：COS 0，TBUT 10.29秒，ST 16.88毫米（10.6微升）。所有组的视力均稳定。2例患者出现无症状、自限性结膜乳头状瘤，1例患者两次发生无并发症的细菌性结膜炎。未观察到剂量限制毒性。5例患者发生严重不良事件，因可能的药物相关系统性感染住院。
系统性巴瑞替尼耐受性良好，可改善oGVHD患者的NIH oGVHD评分和OSD参数，在无既往结膜纤维化的患者中观察到的益处最大。结膜纤维化可能影响疗效，在临床试验患者选择时应予以考虑。
本文末尾的脚注和披露中可能会有专利或商业披露信息。
