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Add-on dupilumab an all-rounder for severe chronic rhinosinusitis

Pearl Toh
09 Oct 2019
Dr Jorge Maspero

Dupilumab significantly improves all disease components of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP)­ — a primarily type 2 inflammatory condition — compared with placebo when both are added to standard of care. Furthermore, the treatment benefit extends to even patients with comorbid nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD), according to a pooled analysis of the LIBERTY NP SINUS-24 and -52* trials presented at ERS 2019.

“CRSwNP with comorbid NSAID-ERD is very severe and difficult to treat, [affecting] an estimated 8-26 percent of CRSwNP patients,” said Dr Jorge Maspero of Fundación Cidea in Buenos Aires, Argentina.

Current standard treatments with intranasal corticosteroids, or systemic corticosteroids when symptoms worsen, come with drawbacks and do not address the underlying inflammatory processes that drive CRSwNP.

“When pharmacological therapy is unsuccessful, surgery can be effective; but without control of the underlying inflammation disease, recurrence is common, resulting in repeated courses of systemic corticosteroids and surgery in a subgroup of patients with nasal polyps,” explained Maspero and colleagues.

“Novel therapies to improve disease control are needed to spare patients from systemic corticosteroids and repeated sinus surgery,” they stressed.

Improvements in all disease aspects

The LIBERTY NP SINUS-24 and -52 trials were two multinational, double-blind studies comparing subcutaneous dupilumab 300 mg Q2W vs placebo, both in addition to standard of care in patients with severe CRSwNP. Patients were stratified by comorbid asthma and/or NSAID-ERD history, and prior nasal polyp surgery — the analysis presented at ERS 2019 evaluated the outcomes specifically in patients with (n=204) and without comorbid NSAID-ERD (n=520) from the pooled study population. [ERS 2019, abstract RCT 3783; Lancet 2019;doi:10.1016/S0140-6736(19)31881-1]

The two trials were similar except that patients in SINUS-52 included an additional arm of dupilumab 300 mg Q2W for the first 24 weeks followed by a Q4W regimen up to week 52. Outcomes at week 24 were reported at ERS as patients in SINUS-24 received treatment for 24 weeks as opposed to 52 weeks in SINUS-52.

Add-on dupilumab significantly reduced nasal polyp size compared with placebo from the first assessment time point through to week 24, regardless of whether patients had comorbid NSAID-ERD or not (p<0.0001 for all time points in both subgroups).

Significant improvements in sinus opacification assessed using LMK-sinus CT** score, patient-reported severity of nasal congestion, and HRQoL*** indicated by SNOT-22# score were also seen with dupilumab vs placebo across all timepoints till week 24 in both subgroups with or without comorbid NSAID-ERD (p<0.0001 for all).

Similarly, disease symptoms and severity were significantly improved with dupilumab vs placebo through to week 24 as reflected in total symptom score and rhinosinusitis disease severity measured on visual analogue scale in both patient subgroups (p<0.0001 for all).

In addition, sense of smell was significantly improved in the dupilumab arm vs the placebo arm, as indicated by the UPSIT## score and daily loss of smell score regardless of NSAID-ERD comorbidity status (p<0.0001 for all).

“These data support the benefits of adding dupilumab to daily standard of care in patients with CRSwNP as a novel approach in treating the entire spectrum of clinical manifestations of the disease,” said Maspero and co-authors.

“Dupilumab treatment also resulted in substantial reductions in the need for systemic corticosteroids and surgery, offering an efficacious treatment for patients with severe CRSwNP who otherwise have few therapeutic options,” they observed.

Regardless of NSAID-ERD comorbidity status, significantly fewer patients receiving dupilumab required systemic corticosteroids (hazard ratios [HRs], 0.219 and 0.281 for patients with and without NSAID-ERD, respectively; p<0.0001 for both) and nasal polyp surgery (HRs, 0.204; p<0.05 and 0.162; p<0.005, respectively) than the placebo group.  

Dupilumab was well tolerated, with the most common adverse events such as nasopharyngitis, headache, and worsening of nasal polyps and asthma occurring more commonly in the placebo arm vs the dupilumab arm, Maspero reported.   

Who and when to treat?

“Physicians are now faced with decisions of when to start dupilumab treatment and in which patients with CRSwNP,” wrote Dr Whitney Stevens from Northwestern University Feinberg School of Medicine in Chicago, Illinois, US in a linked commentary. [Lancet 2019;doi:10.1016/S0140-6736(19)32133-6]   

“[In the study,] subsets of patients with CRSwNP who also had … NSAID-ERD had similar degrees of benefit with dupilumab compared with those of the overall study population,” she continued. “[Also,] 12 weeks after discontinuing dupilumab, nasal polyp size and symptoms returned nearly to levels of patients receiving placebo, suggesting that longer term treatment with dupilumab might be necessary.”

 

 

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Most Read Articles
01 Dec 2019
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Roshini Claire Anthony, 6 days ago

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