Trial Results Show Benefits of Dupilumab in Patients With Severe CRS With Nasal Polyps
Results from 2 large clinical trials show that dupilumab is associated with clinical improvements in symptoms of chronic rhinosinusitis (CRS) with nasal polyps.
The results of the phase 3 trials, LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52, were published in the Lancet; in June, the FDA approved dupilumab for the treatment of CRS with nasal polyps based on the data from these trials, making it the first biologic to be approved for adults with inadequately controlled disease.
In the multinational, randomized, double-blind, placebo-controlled trials, investigators assessed the efficacy and safety of dupilumab when added to standard therapy (intranasal corticosteroids) among adults with severe CRS with nasal polyps that was uncontrolled by the standard of care. In SINUS-24, patients were randomly assigned to receive either 300 mg dupilumab every 2 weeks or placebo. In SINUS-52, patients were randomly assigned to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab 300 mg every 2 weeks for 24 weeks followed by dupilumab 300 mg every 4 weeks, or placebo.
The improvement in endoscopic nasal polyp score (NPS) by week 24 was significantly greater with dupilumab than placebo in both studies, and patients receiving dupilumab also reported significantly improved nasal congestion. Improvements in both NPS and congestion were observed early in the course of treatment (within 4-8 weeks) and continued through the end of treatment.
Furthermore, the dupilumab groups had significantly improved Lund-Mackay computed tomography scores at week 24 compared with placebo, and improvements in 22-item Sino-Nasal Outcome Test scores in the dupilumab groups were both clinically important and statistically significant. In both trials, the proportion of patients with anosmia decreased with treatment in the groups receiving dupilumab (SINUS-24, from 74% at baseline to 24% at week 24; SINUS-52, 79% at baseline to 30% at week 24) while almost no change was seen in the placebo group.
Patients who received dupilumab every 2 weeks were significantly less likely to require systemic corticosteroid use or nasal polyp surgery during the 52-week study period than those receiving placebo (12.5% vs 41.8%, respectively; hazard ratio, 0.243; P <.0001).
In subsets of patients with comorbid asthma, dupilumab significantly improved lung function and asthma control compared with placebo, and these improvements were similar in patients with high and low baseline blood eosinophil counts. The study authors noted that this finding suggests that blood eosinophil levels do not provide additional specificity in identifying which patients with CRS with nasal polyps and comorbid asthma are more likely to respond to dupilumab.
Results of pooled safety analyses showed that adverse events were less common in the dupilumab group than the placebo group over the 24-week treatment period. The most commonly reported were nasopharyngitis, nasal polyps, headache, asthma, epistaxis, and injection-site erythema, which were each more frequent with placebo than with dupilumab. Over the 52-week period in SINUS-52, the 2 dupilumab groups had slightly more frequent occurrences of cough, bronchitis, arthralgia, accidental overdose, and injection-site reactions than the placebo group.
According to the study authors, adding dupilumab to the treatment regimen can alleviate the high symptom burden and quality-of-life impacts seen with CRS with nasal polyps by providing “early, significant, and clinically meaningful improvements across all aspects of disease.” Because the trial results showed continuing improvement throughout the study period and diminished effects after discontinuation of dupilumab, the researchers suggested that continued suppression of type 2 inflammation is necessary to maintain disease control.
“These data support the benefits of adding dupilumab to daily standard of care in patients with [CRS with nasal polyps] as a novel approach in treating the entire spectrum of clinical manifestations of the disease, a predominantly type 2 inflammatory condition, as well as the frequently associated type 2 lower airway comorbidities,” the study authors concluded. They added that dupilumab treatment offers efficacious therapy for patients with severe disease who have few other treatment options.
Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials [published online September 19, 2019]. Lancet. doi: 10.1016/S0140-6736(19)31881-1.