{
    "abstract": "Current medical therapies in idiopathic subglottic stenosis (iSGS) are insufficient in preventing the development and progression of scar tissue. An inhibitor of mammalian target of rapamycin, everolimus is an immunosuppressive medication shown to be effective in reducing fibrosis across a variety of fibroproliferative disorders, including preclinical models of iSGS.\nTo evaluate the effect of oral everolimus on postoperative recurrence of stenosis in iSGS.\nThis open-label, single-arm, phase 1, nonrandomized clinical trial analyzed 7 perimenopausal participants diagnosed with iSGS and followed-up at a tertiary care academic center for 6 months after dilation surgery. The trial was conducted from November 1, 2022, through May 15, 2024.\nParticipants took a 1.5-mg daily oral dose of everolimus for 42 days after surgery.\nThe primary outcome measure was safety as determined by adverse events. Secondary outcome measures included change in peak expiratory flow from baseline through 180 days after surgery; change in the luminal area, measured by computed tomographic (CT) scan, from the 14th and the 180th day; and changes in quality-of-life scores.\nOf the 8 perimenopausal participants, 7 (median age, 50 years [IQR, 45.0-52.5 years]) completed the study. Compared with baseline at all time points, there was an increase in peak expiratory flow. The median difference in liters per minute was 125 (95% CI, 90-270) on day 7 after surgery; 150 (95% CI, 110-290) on day 14; 138 (95% CI, 116-280) on day 28; 160 (95% CI, 100-270) on day 42; 155 (95% CI, 110-270) on day 60; 140 (95% CI, 100-270) on day 90; and 100 (95% CI, 20-240) on day 180. A decrease in the CT luminal area was observed from the day-14 measure to the day-180 measure (median stenosis, 7.2%; IQR, 1.9%-15.4%). During the trial, 1 participant (14.3%) each developed oral ulcers, a urinary tract infection, and a skin infection.\nIn this interventional nonrandomized clinical trial of iSGS, adjuvant everolimus was well-tolerated with minor adverse events. Participants sustained postdilation peak expiratory flow for 13 weeks. These results support proceeding to a phase 2 trial to study drug efficacy and a more detailed investigation of adverse effects.\nClinicalTrials.gov Identifier: NCT05153668.",
    "authors": [
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Raymond J",
            "initials": "RJ",
            "lastname": "So"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Samuel L",
            "initials": "SL",
            "lastname": "Collins"
        },
        {
            "affiliation": "Department of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Sarah",
            "initials": "S",
            "lastname": "Collins"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Laura",
            "initials": "L",
            "lastname": "Mafla"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Yee",
            "initials": "Y",
            "lastname": "Chan-Li"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Ioan",
            "initials": "I",
            "lastname": "Lina"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.",
            "firstname": "Alexander",
            "initials": "A",
            "lastname": "Gelbard"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Kevin M",
            "initials": "KM",
            "lastname": "Motz"
        },
        {
            "affiliation": "Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.",
            "firstname": "Alexander T",
            "initials": "AT",
            "lastname": "Hillel"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1001/jamaoto.2024.2886\n10.1001/jamaoto.2019.3022\n10.1002/lary.29013\n10.1177/01945998211028163\n10.1016/j.otot.2023.05.009\n10.1002/lary.30449\n10.1002/lary.29675\n10.3892/ijo.2021.5234\n10.5500/wjt.v4.i2.133\n10.1111/bph.15898\n10.1016/j.lfs.2021.120150\n10.1056/NEJMoa1610227\n10.1039/C8BM01623B\n10.1172/jci.insight.158456\n10.1080/14737175.2019.1635457\n10.1002/lary.29760",
    "journal": "JAMA otolaryngology-- head & neck surgery",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-09-26",
    "pubmed_id": "39325463\n31670805\n32820819\n34253069\n36286239\n34117778\n34132370\n25032102\n35726496\n34793770\n27797291\n30874257\n37159282\n31335226\n34309022",
    "results": "Of the 8 perimenopausal participants, 7 (median age, 50 years [IQR, 45.0-52.5 years]) completed the study. Compared with baseline at all time points, there was an increase in peak expiratory flow. The median difference in liters per minute was 125 (95% CI, 90-270) on day 7 after surgery; 150 (95% CI, 110-290) on day 14; 138 (95% CI, 116-280) on day 28; 160 (95% CI, 100-270) on day 42; 155 (95% CI, 110-270) on day 60; 140 (95% CI, 100-270) on day 90; and 100 (95% CI, 20-240) on day 180. A decrease in the CT luminal area was observed from the day-14 measure to the day-180 measure (median stenosis, 7.2%; IQR, 1.9%-15.4%). During the trial, 1 participant (14.3%) each developed oral ulcers, a urinary tract infection, and a skin infection.",
    "title": "Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial.",
    "xml": "<Element 'PubmedArticle' at 0x7885048c4e00>"
}