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Stapokibart Improves Rhinosinusitis With Nasal Polyps
Addition of the monoclonal antibody stapokibart significantly improved nasal polyps and nasal congestion in adults with uncontrolled chronic rhinosinusitis with nasal polyps, based on new data from 179 individuals.
Biologics are now more commonly used as treatments for chronic rhinosinusitis with nasal polyps (CRSwNP), and monoclonal antibodies have emerged as significantly more effective than other biologics for these patients, wrote Shen Shen, MS, of Capital Medical University, Beijing, China, and colleagues.
In a study known as CROWNS-2 published in JAMA , the researchers randomly assigned 180 adults with CRSwNP to stapokibart (300 mg subcutaneously) or a placebo injection every 2 weeks for 24 weeks. All participants also received 100 μg of mometasone furoate per nostril once a day as background treatment before and during the study.
The co-primary endpoints were changes in nasal polyp score and nasal congestion score from baseline to 24 weeks in the study population overall and in the subgroup with eosinophilic chronic rhinosinusitis with nasal polyps. The 24-week double-blind period was followed by an open-label extension to 52 weeks. Key secondary endpoints included the percentage of patients who achieved improvement of 1 point or more on nasal polyp scores and 2 points or more on nasal polyp scores.
The final analysis included 90 individuals in the stapokibart group and 89 in the placebo group. The mean age of the study population was 45 years, and approximately one third were women. The mean duration of CRSwNP was 6.0 years, and 139 patients (77.7%) had eosinophilic CRSwNP.
Study Outcomes
Compared with placebo patients at 24 weeks, patients in the stapokibart group had a significant reduction in polyp size, with least-squares mean (LSM) changes in nasal polyp score from baseline of -2.6 and -0.3 points, respectively ( P < .001).
Similarly, patients in the stapokibart group had a significantly greater LSM change in nasal congestion score from baseline to week 24 than those in the placebo group (-1.2 points vs -0.5 points, respectively; P < .001).
Nearly all of the patients treated with stapokibart (96.5%) had a reduction in nasal polyp score of at least 1 point, and 89.5% had a reduction of at least 2 points after 52 weeks.
The improvements in both primary endpoints were even greater among patients with eosinophilia, with an LSM change of -3.0 vs -0.04 for nasal polyp scores and -1.3 vs -0.5 for nasal congestion scores in stapokibart vs placebo patients, respectively.
The overall incidence of adverse events in the first 24 weeks of the study was similar for the stapokibart and placebo groups. The most common adverse events were upper respiratory tract infections, COVID-19, and unconfirmed but suspected COVID-19. Serious adverse events were rare and similar between the stapokibart and placebo groups (2.2% vs 1.1%).
However, higher rates of arthralgia and hyperuricemia were reported with stapokibart than with placebo (7.8% vs 0% and 5.6% vs 1.1%, respectively).
The findings were limited by several factors, including the lack of data on aspirin-exacerbated respiratory disease, the small numbers of patients, and the inclusion only of patients in China, the researchers noted.
However, the results support the potential of stapokibart to reduce nasal polyp size and symptom severity in adults with severe CRSwNP, they concluded.
Emergence of Endotyping
The significant reduction in polyp score was the study's most notable finding, according to an accompanying editorial.
'The emergence of biologic therapies for chronic rhinosinusitis with nasal polyps has brought the concept of inflammatory endotyping to the forefront of this condition,' wrote Michael P. Platt, MD, of Boston University Chobanian & Avedisian School of Medicine, Boston; Stacey T. Gray, MD, of Harvard Medical School, Boston; and Anju T. Peters, MD, of Northwestern University Feinberg School of Medicine, Chicago.
The current study included a majority of individuals with eosinophilic CRSwNP, and the successful reduction in polyp size was based on correct identification of this T2 endotype, as stapokibart targeted T2 inflammation, they said. However, choosing the appropriate biologic therapy for uncontrolled CRSwNP with nasal polyps also requires consideration of other comorbid atopic diseases and disease pathogenesis, with shared decision-making, they added.
Tuning in to Eosinophilia
'Currently, three biologics are approved for CRSwNP in the US, with additional agents likely to follow,' said Michael S. Blaiss, MD, an allergist and clinical professor at the Medical College of Georgia at Augusta University, Augusta, Georgia, in an interview.
'What distinguishes this trial is that the investigators specifically defined and studied eosinophilic CRSwNP,' said Blaiss, who was not involved in the study. 'In this subgroup, the biologic demonstrated significant efficacy, providing important data for this population of CRSwNP sufferers,' he said.
The study findings were not unexpected, as stapokibart has a similar mechanism of action to dupilumab, said Blaiss. 'Both target the IL-4Rα [interleukin-4 receptor subunit alpha] receptor, albeit at different binding sites and affinities, and dupilumab is already FDA-approved for CRSwNP, so efficacy was expected,' he said. 'However, safety findings warrant attention,' he emphasized. The significantly greater occurrence of arthralgia and hyperuricemia in stapokibart vs placebo patients deserves further evaluation in larger and longer studies, Blaiss said.
'If approved, this biologic would provide an additional treatment option for patients with moderate to severe CRSwNP,' Blaiss told Medscape Medical News . However, its advantages over currently available biologics remain unknown, as the dosing schedule of every 2 weeks does not improve convenience, he noted.
'Head-to-head comparative studies are needed, similar to the recent dupilumab vs omalizumab trial in CRSwNP, to determine whether one biologic is clinically superior,' said Blaiss. 'Furthermore, evaluation in noneosinophilic CRSwNP is necessary, as the present study included too few patients in this subgroup for meaningful statistical analysis,' he added.
