@article {1593828,
	title = {Efficacy and Safety of 1\% Progesterone Gel to the Forehead for Ocular Chronic Graft-versus-Host Disease},
	journal = {Transplant Cell Ther},
	volume = {27},
	number = {5},
	year = {2021},
	month = {2021 May},
	pages = {433.e1-433.e8},
	abstract = {There is no Food and Drug Administration-approved treatments for ocular chronic graft-versus-host disease (oGVHD) to date, and current therapeutic options are limited. Forehead application of 1\% progesterone gel provides corneal antinociception in preclinical models, suggesting it may be useful in alleviating ocular irritations. This study was conducted to evaluate the efficacy and safety of 1\% progesterone gel in treating moderate to severe symptomatic oGVHD. Thirty-three patients with oGVHD following allogeneic stem cell transplantation were enrolled in this single-center, sponsor-initiated, prospective exploratory randomized double-masked placebo-controlled phase II clinical trial. The inclusion criteria included a National Institutes of Health consensus score of >=2, moderate to severe ocular discomfort level, and receipt of a stable immunosuppression regimen. Twenty-one of the 22 patients in the progesterone arm and all 11 patients in the placebo arm completed the course of twice-daily forehead drug application for 10 weeks. The changes from baseline of self-reported ocular symptom scores and physician-recorded cornea fluorescein staining scores were analyzed using mixed-model repeated-measures regression model in an intention-to-treat population. The 33 patients included 12 women and 21 men, with a median age of 66 years (range, 24 to 75 years). At 10 weeks, there was a significant reduction in ocular symptoms from baseline in the progesterone group compared with the placebo group in symptom frequency (-30.7 versus -2.2; P \&lt; .001) and severity (-19.8 versus +1.6; P\&nbsp;=\&nbsp;.005). At 10 weeks, there was also greater reduction of cornea fluorescein staining centrally (-1.2 versus +.1; P\&nbsp;=\&nbsp;.001) and inferiorly (-1.4 versus -0.2; P\&nbsp;=\&nbsp;.005). No difference was noted in superior cornea staining. There were no severe adverse events in the progesterone group. Forehead\&nbsp;application\&nbsp;of 1\% progesterone gel\&nbsp;significantly\&nbsp;improved ocular signs and symptoms within 10 weeks. It appears to be a safe and effective new therapy for oGVHD, and a novel mechanism for neuroaxis drug delivery. A multicenter phase III clinical trial is planned for further validation.},
	issn = {2666-6367},
	doi = {10.1016/j.jtct.2021.02.008},
	author = {Luo, Zhonghui K and Domenech-Estarellas, Edgar A and Han, Amy and Lee, Do and Khatri, Ram and Wahl, Jonathan L and Cutler, Corey and Armand, Philippe and Antin, Joseph H and Koreth, John and Gooptu, Mahasweta and Alyea, Edwin P and Soiffer, Robert J and Ho, Vincent T}
}
