Upregulation of Antiviral Biomarkers in Sputum Cells Following Administration of Inhaled Interferon Beta to Patients with COPD

Monk, Phillip; Reynolds, Sarah J.; Lunn, Kerry; Beegan, Rona; Roberts, James; Tear, Victoria

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a4045

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“…All five assessed ISGs in sputum cells were upregulated following administration of SNG001 in Part 1, with the initial upregulation in Part 2 (in response to the viral infection) prolonged in those patients receiving SNG001, showing that SNG001 boosted lung antiviral responses. Importantly, the fold-changes in sputum Mx1 and OAS1 following administration of SNG001 in Part 1 were consistent with changes in a previous asthma study [ 21 ], suggesting that the administered dose is similarly effective in younger patients with asthma and in older patients with COPD – both of whom are at increased risk from viral infections. Furthermore, in Part 2, the post-hoc analysis in patients who had a positive test for human rhinovirus (the most commonly detected virus during COPD exacerbations [ 22 ]) suggested that viral clearance was enhanced by SNG001 – with a more rapid decrease with SNG001 than placebo.…”

Section: Discussionsupporting

confidence: 84%

Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD

Monk,

Brookes,

Tear

et al. 2024

Respir Res

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Background Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. Methods In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Results In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. Conclusions Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. Trial registration EU clinical trials register (2017-003679-75), 6 October 2017.

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Section: Discussionsupporting

confidence: 84%