A Randomized, Open-labeled, Multicenter Clinical Trial to Compare the Efficacy and Safety of On-demand and Continuous Administration of Nasal Spray in the Treatment of Moderate-to-severe Persistent Allergic Rhinitis

Background/Significance The prevalence of AR is increasing worldwide. A large number of studies have shown that AR has a significant adverse impact on the quality of life especially in the moderate-to-severe AR population. However, as AR is not a fatal disease, only a small proportion of AR patients will go to hospital to seek professional medical advice. They have a tendency to do so only when their AR-related symptoms become intolerable, which led to a dramatic low level of AR control. It is well known that uncontrolled AR has been identified as a high-risk factor of exacerbation of asthma and chronic rhinosinusitis. In AR patients, 40% will develop asthma and up to 30% will develop chronic sinusitis. Adequate treatment of AR always help to improve patients' quality of life and also reduce the risk of AR related complications.

To achieve the goal of AR control, long-term treatment is always needed. AR is an IgE-mediated inflammatory disease induced by allergen exposure. Our previous study had shown that more than 90% of AR patients in central China were induced by house dust mite (HDM), a perennial indoor allergen. HDM exposure leads to persistent allergic inflammation in nasal mucous and causes periodic exacerbation of AR symptoms. INS is currently the cornerstone medication to inhibit the allergic inflammation and is recommended as the first-line medication for moderate-to-severe AR. However, the anti-inflammation effect can only be achieved after administrate for several days to two weeks. For this reason, the ARIA guideline suggests to use INS regularly for 2-4 weeks, then step down gradually. In another side, antihistamine belongs to symptom-relief medication, which has been proven to act within 5min for nasal spray and 30min for oral route. Antihistamine is also recommended as first-line medication for mild AR patients and combined with INS for moderate-to-severe AR patients. Our previous studies had shown that if AR patients were treated according to the current guideline for 15 days, only 72.3% of them were controlled. However, if the treatment extended to 60 days, more than 95% would achieve AR controlled.

Low adherence is always a considerable issue for long-term treatment. In asthma patients, more than 80% of patients taken β2 agonist as needed to relieve their symptom instead of daily using inhalant corticosteroids. For AR, the adherence to treatment recommendation was below 30% in the real world. Most AR patients wouldn't take their medication continuously for 14 days as they usually suffered from several episodes of short-term AR symptoms. They have a strong preference for a treatment which can provide both a rapid onset of action and clinically-relevant symptom relief.

In this study, investigators will compare the AR control level of on-demand treatment versus daily maintenance treatment in moderate-to-severe AR patients. If the on-demand treatment can achieve similar or non-inferior AR control rate as daily maintenance treatment, it will be very helpful to optimize current management of AR patients.

Preliminary Data A recent study in 150 pollen-induced AR children found that the percentage of symptom-free-day was in favor of INS on-demand (30%) compared with low dosage INS daily (22%), although the statistical significance was not achieved. It implied that on-demand fluticasone propionate treatment was at least as effective as a regular treatment at a lower dose. The authors concluded that an on-demand INS strategy has the advantage of a lower overall corticosteroid exposure and less costs.