In a recent study published in EClinicalMedicine, researchers assessed the efficacy and safety of stapokibart as an add-on therapy in patients with moderate-to-severe uncontrolled seasonal allergic rhinitis (SAR).
Study: Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. Image Credit: wavebreakmedia/Shutterstock.com
Background
Allergic rhinitis (AR), affecting up to half the global population, is an Immunoglobulin E (IgE)-mediated inflammatory condition of the nasal mucosa, leading to symptoms like sneezing, congestion, and often ocular discomfort.
It poses a significant socio-economic burden, with costs reaching €50 billion annually. AR divides into SAR and perennial forms, with SAR, triggered by outdoor pollen, showing higher inflammation and more severe symptoms.
Despite treatments like antihistamines and corticosteroids, over 60% of SAR patients report inadequate symptom control. Biologics targeting type 2 inflammation, such as omalizumab, have shown benefits, yet their role in post-standard care remains unclear.
Further research is needed to conclusively determine the effectiveness and safety of biological treatments in managing uncontrolled SAR and to optimize patient care strategies.
About the study
In the present comprehensive phase 2 trial conducted across six sites in China, researchers embarked on a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of stapokibart in treating SAR.
Participants, aged 18 to 65 with a documented history of SAR and insufficient response to conventional treatments, were randomized in a 1:1:1 ratio to receive stapokibart 300 mg either weekly or biweekly or a placebo, alongside mometasone furoate nasal spray and oral loratadine over a 4-week treatment period, followed by an 8-week follow-up.
The study rigorously adhered to ethical standards, following the Declaration of Helsinki and Good Clinical Practice, with ethics committee approvals from each center.
It strictly selected participants with confirmed SAR, significant pollen exposure, and considerable baseline symptoms. It used comprehensive assessments via the Rhinoconjunctivitis Quality-of-Life Questionnaire, including daily nasal and ocular symptom scores and life quality.
It thoroughly analyzed efficacy and safety, focusing on nasal symptom changes over two weeks, alongside secondary evaluations of symptom variations, life quality, and treatment timings. Safety was closely monitored, including adverse events, lab tests, and vital signs.
Statistical analyses were conducted with precision, aiming to demonstrate the superiority of stapokibart over placebo with adjusted type I error rates.
A sample size calculation ensured adequate power to detect significant differences, accounting for potential dropouts.
Efficacy endpoints were analyzed using an Analysis of Covariance (ANCOVA) model, with a rigorous plan for handling missing data and ensuring robust results.
Study results
Between August 17 and December 28, 2022, the present study screened 172 patients for SAR, enrolling 93 from four centers, with 92 receiving treatment. The participants, averaging 37 years old and mostly female, had SAR for an average of 7.6 years.
Despite treatment, stapokibart did not significantly outperform placebo in reducing total nasal symptom scores (rTNSS) over two weeks.
However, when administered biweekly, stapokibart showed notable improvement in nasal congestion and ocular symptoms, with significant reductions in both nasal and ocular symptom scores compared to placebo.
The study observed mild to moderate treatment-emergent adverse events, with a lower incidence in the stapokibart groups compared to placebo.
Further exploratory analyses illuminated that biweekly stapokibart led to more days with mild or no symptoms, alongside a noteworthy decrease in inflammation markers.
Especially notable was the discovery from subgroup analyses that individuals with higher initial eosinophil counts exhibited more pronounced benefits from the biweekly stapokibart regimen.
Despite the primary outcomes not demonstrating significant differences, the study's secondary and exploratory findings hint at stapokibart's potential advantages, particularly for patients with elevated eosinophil levels.
This insight propels the argument for additional research into stapokibart's role in treating SAR, suggesting that its real value may lie in a more targeted application based on specific patient profiles.
Conclusions
To summarize, the trial found that while stapokibart, administered either weekly or biweekly, did not significantly change total nasal symptom scores over placebo, it effectively improved nasal and ocular symptom scores in SAR patients, especially those with high eosinophil counts.
It was the first to assess biologics as an add-on during pollen exposure for patients with uncontrolled SAR.
Subgroup analysis revealed significant symptom improvements in patients with high eosinophil levels, aligning with stapokibart's targeted inflammation mechanism.
Despite a generally well-tolerated safety profile, no linear dose-response relationship was observed, highlighting the need for further research.
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