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Entyvio (Vedolizumab) and Tysabri (Natalizumab) & Interstitial Lung Disease

    Basic Details
    Status
    Complete
    Last Updated
    Wednesday, November 6, 2024
    Original Posting Date
    Health Outcome(s)
    interstitial lung disease (ILD)
    Purpose
    Drug and Outcome Analysis
    Meets requirements of FD&C Act Sec 505(o) prior to requiring a PMR
    No
    Study Summary

    Entyvio (vedolizumab) is an integrin receptor antagonist indicated for the treatment of adult patients with moderately to severely active ulcerative colitis and Crohn’s disease, the two main disorders that comprise inflammatory bowel disease (IBD). Based on two previous Periodic Safety Reports, the European Medicines Agency (EMA) evaluated cases of interstitial lung disease (ILD) in vedolizumab users and concluded that the contribution of vedolizumab could not be excluded. There are also limited available data on the background incidence rates of ILD in patients with IBD, as well as the incidence rates of ILD in IBD patients treated with vedolizumab or other biologics. Due to this, FDA issued a Newly Identified Safety Signal (NISS) in January 2023 to facilitate evaluation and management of this potential risk for ILD. Tysabri (natalizumab), another integrin receptor antagonist indicated for treatment of multiple sclerosis and Crohn’s disease, was also evaluated for ILD as part of this NISS. The FDA pursued studies in the Sentinel System to better understand the incidence of ILD in IBD patients treated with vedolizumab, natalizumab, or other advanced therapies. Specifically, Sentinel System studies estimated the incidence rate of ILD among patients with IBD overall and separately among patients treated with vedolizumab, natalizumab, or other advanced therapies.

    Sentinel System results did not indicate an increased incidence rate of ILD in patients treated with vedolizumab or natalizumab for IBD. The incidence rates of ILD for patients with IBD treated with integrin receptor antagonists approximates the ILD incidence rates observed separately in IBD patients who initiated and actively used advanced therapies other than an integrin receptor antagonist or patients with IBD with a history of treatment with advanced therapies other than an integrin receptor antagonist.  

    As part of the NISS evaluation, FDA used findings from the Sentinel analysis to support contextualizing the identified safety signal and provide additional data on the burden of disease. Based on the entire body of evidence evaluated as part of the NISS, including 18 postmarketing cases of non-infectious ILD with vedolizumab or natalizumab in the FDA Adverse Event Reporting System (FAERS) database and 21 cases of ILD in vedolizumab-treated patients published in the medical literature, FDA approved a safety-related labeling supplement request for vedolizumab on April 18, 2024. This safety-related labeling update incorporated the terms, “interstitial lung disease, pneumonitis” into the Postmarketing Experience subsection of the Prescribing Information.