Topical tretinoin in chronic rhinosinusitis with nasal polyps: a randomized clinical trial

Author(s)

Antonio, Marcelo Augusto ; Lima Marson, Fernando Augusto ; Contrera Toro, Mariana Dalbo ; Sampaio, Marcelo Hamilton ; Barreto, Icleia Siqueira ; Dertkigil, Sergio San Juan ; Inoue Sakuma, Emerson Taro ; Guadagnini, Dioze ; Sakano, Eulalia

• Document type: Journal article
• Source: INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY; v. 11, n. 8, p. 10-pg., 2021-02-14.

Abstract

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is usually treated with corticosteroids, given their anti-inflammatory effects. Unlike the nasal administration, the oral and ocular use of tretinoin, an immunoregulatory drug, is well established. Therefore, tretinoin was thought to act on nasal polyps, and possible adverse and/or therapeutic effects were investigated. Methods A first-in-human open-label trial was conducted enrolling patients with CRSwNP randomized into: a control group (CTR, n = 15), treated with budesonide for 24 weeks; and an intervention group (TRT, n = 15), who received budesonide and 0.1% tretinoin in the last 12 weeks. Primary endpoint included histopathological analysis and tissue immunoassay (Multiplex) for tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta, IL-4, IL-5, IL-13, and matrix metalloproteinase 9 (MMP-9) at 12 and 24 weeks. Secondary endpoints were: adverse events report, endoscopy (modified Lund-Kennedy scoring system [LKS]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), and olfactory test (Connecticut Chemosensory Clinical Research Center) at baseline, at 12 weeks, and at 24 weeks, in addition to serum biochemistry and tomographic findings (Lund-Mackay computed tomography [CT] staging system [LMS]) at baseline and 24 weeks. Results TRT showed less microscopic edema (2/13 [15.4%] vs 8/13 [61.5%]; p = 0.044) as well as no increase in cytokines levels. All adverse events were categorized as "grade 1" (asymptomatic; mild). The most interesting part of this study was the improvement in smell between baseline (T0) and week 24 (T2) in TRT only (p = 0.041). Conclusion Transnasal tretinoin associated with budesonide was safe and well tolerated, and it should be investigated as a treatment option for some CRSwNP endotypes. (c) 2021 ARSAAOA, LLC. (AU)

• FAPESP's process: 17/23802-6 - Evaluation of the function of the CFTR protein by evaporimetry in patients with chronic rhinosinusitis, with and without polyposis
• Grantee: Eulalia Sakano
• Support Opportunities: Regular Research Grants