Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps

Background Among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), randomized clinical trials (RCTs) of biologics, such as anti-interleukin-4/interleukin-13 (dupilumab) and anti-immunoglobulin E (omalizumab), have demonstrated efficacy compared with intranasal corticosteroids (INCS). However, no head-to-head RCTs exist between biologics. Objective To perform an indirect treatment comparison (ITC) of the efficacy of biologics plus INCS versus placebo (INCS) as a common comparator. Methods Embase, MEDLINE, and Cochrane were searched for RCTs of biologics in CRSwNP. Bucher ITCs were performed for outcomes at week 24: nasal polyp score (NPS) (range, 0-8), nasal congestion (NC) (range, 0-3), loss of smell (range, 0-3), University of Pennsylvania Smell Identification Test (range, 0-40), total symptom score (range, 0-12), 22-item sinonasal outcome test (range, 0-110), and responder analyses based on NPS or NC improvement of one point or greater. Results Assessment of trial design, baseline characteristics, and outcome measures suggested that ITC was feasible with four phase 3 RCTs: dupilumab SINUS-24 and SINUS-52 (NCT02912468/NCT02898454) and omalizumab POLYP 1 and POLYP 2 (NCT03280550/NCT03280537). In the intent-to-treat population, dupilumab had significantly greater improvements from baseline to week 24 versus omalizumab across key outcomes: NPS (least squares mean difference [95% confidence interval], −1.04 [−1.63 to −0.44]), NC (−0.35 [−0.60 to −0.11]), loss of smell (−0.66 [−0.90 to −0.42]), University of Pennsylvania Smell Identification Test (6.70 [4.67-8.73]), and total symptom score (−1.18 [−1.95 to −0.41]). Improvement in the 22-item sinonasal outcome test was greater in dupilumab versus omalizumab but was not statistically significant. Dupilumab patients were significantly more likely to achieve one-point improvement or greater in NPS (odds ratio [95% CI] = 3.85 [1.82-7.04]) and NC (2.13 [1.12-4.04]) versus omalizumab. Conclusions Although ITCs have limitations, these results demonstrated that dupilumab had consistently greater improvements in key CRSwNP outcomes versus omalizumab at week 24.