Study compares as-needed vs regular use of fluticasone furoate nasal spray to treat perennial allergic rhinitis patients

Both regular and as-needed use of intranasal corticosteroids displayed comparable improvement in the  quality of life and nasal symptoms in patients having moderate-to-severe perennial allergic rhinitis. 

Allergic rhinitis, one of the most common diseases worldwide, has a prevalence of up to 40% in adults and 50% in children. It substantially impairs the patient's quality of life. However, patients suffering from allergic rhinitis do not seek suitable treatment and do not show compliance to treatment, thus resulting in elevated economic costs.

A novel classification of allergic rhinitis has been introduced by Allergic Rhinitis and its Impact on Asthma (ARIA). The duration is categorized into intermittent and persistent patterns whereas the severity is categorized into mild and moderate-to-severe. Due to troublesome symptoms, the moderate-to-severe, persistent allergic rhinitis is still a problem globally.

For alleviating allergic rhinitis, the daily use of intranasal corticosteroids is advocated. Fluticasone furoate nasal spray, an intranasal corticosteroid, has been approved for managing seasonal as well as perennial allergic rhinitis. It has low systemic bioavailability and improved affinity for the glucocorticoid receptors. The majority of allergic rhinitis patients do not strictly follow the guidelines. They use their medications as-required when their symptoms are not adequately controlled.

A study by Wang et al. depicted that the adherence to intranasal corticosteroid was 60% in patients receiving short message reminders and only 28% in the control group. Even taking only 20% of the expected dose, the visual analog scale (VAS) indicated remarkable improvements in comparison with the baseline.

According to the findings of a study conducted by Andersson et al, pretreatments with intranasal corticosteroid for a short period were able to eliminate nasal hyperresponsiveness from an experimental allergen in seasonal allergic rhinitis patients.

In patients with seasonal allergic rhinitis, as-needed use of fluticasone propionate nasal spray illustrated superior efficacy to placebo in minimizing allergic inflammation and nasal symptoms. Only fewer treatment-emergent adverse events were reported. Thus, the as-needed use of intranasal corticosteroid, which has never been analyzed in patients with perennial allergic rhinitis, requires well-controlled trials to show its efficacy in comparison to regular use.

Rationale behind research:

Previous evidence has reported that intranasal corticosteroid should be regularly used for managing perennial allergic rhinitis.  But till date, no studies have examined “as-needed” use. Therefore, this large study was performed.

Objective:

A six-week randomized controlled trial (RCT) was conducted to investigate the efficacy of as-needed and regular use of intranasal corticosteroids in patients having moderate-to-severe  perennial allergic rhinitis.

Study outcomes

• The primary outcome was a comparison of the mean alteration from baseline of total nasal symptom score (TNSS) between fluticasone furoate-as-needed group and FF-regular group over the six-week treatment period
• Other secondary outcomes included the mean alteration from baseline of individual nasal symptom score, Rhinoconjunctivitis Quality of Life Questionnaire (RCQ-36), nasal peak inspiratory flow (NPIF), cumulative dose of fluticasone furoate, adverse events rates between the two regimens, and mean alteration from baseline of TNSS within each group

FF: Fluticasone furoate

Outcomes

Baseline: There were no significant differences reported at baseline.

Study outcomes:

• The difference in mean alteration of TNSS between the two groups was not found to be significant in the sixth week (1.21 points; 95% CI, -0.08 to 2.49; P = 0.066)
• The fluticasone furoate-regular group tended towards a higher improvement in TNSS
• Compared to the fluticasone furoate-as-needed group, the fluticasone furoate-regular group had a higher mean alteration of NPIF than at week 6 (-19.21 L/min; 95%CI, -33.54, -4.89; P=0.009)
• Similar improvement in RCQ-36 was noted in both groups
• The mean cumulative fluticasone furoate dose in the as-needed group was 51% that of the regular group

Fig.2: Intention-to-treat analysis of the mean change of total nasal symptom score (TNSS) from baseline 

This is the first RCT to explore the safety and efficacy of intranasal corticosteroids administered on an “as-needed” basis in comparison with “regular” use in moderate-to-severe, persistent perennial allergic rhinitis patients. During weeks 1-6, no considerable difference in mean alteration of TNSS between the two groups was witnessed. However, a tendency towards improved TNSS was noted in the regular group.

From week 3-6, the regular group had a higher mean alteration of NPIF compared to the as-needed group. A similar improvement in the RCQ-36 score was noted in both groups. At week 6, the regular group demonstrated superiority to the as-needed group and improvement in sneezing scores and nasal congestion.

The study conducted by Juniper et al in 1990 and 1993 (different blinding methods) compared regular and as-needed use of beclomethasone dipropionate to cure seasonal allergic rhinitis. The 1990 study revealed that regular use had fewer symptoms and better quality of life during the pollen season compared to as-needed use. However, the validity of the conclusion is limited because some patients in the as-needed cohort may have underused their devices due to participant blinding.

In 1993, this study was thus repeated in an unblinded fashion. The symptoms and quality of life were not considerably different, but there was a tendency for TNSS to be better in the regular use arm. In both studies, the actual differences between the regular and as-needed use were small, comparable, and clinically insignificant.

A study by Jen et al. illustrated that the as-needed use of fluticasone propionate nasal spray demonstrated better efficacy compared to placebo in alleviating symptoms and allergic inflammation in patients with seasonal allergic rhinitis. Kaszuba et al. found that compared to the as-needed H1-receptor antagonists, the as-needed fluticasone propionate nasal spray was more effective.

Dykewicz et al. showed that in seasonal allergic rhinitis patients, the as-needed fluticasone propionate was effective and also minimized adverse events in comparison to regular use. Kirtsreesakul et al showed that self-adjusted use of triamcinolone acetonide nasal spray improved TNSS by 60% with about one-third of the total intranasal corticosteroids dosage of daily use. These studies depict that as-needed use of intranasal corticosteroids may prevent unnecessary use, especially when symptoms are minimal.

Compared to the placebo, fluticasone furoate takes 1-8 days to become effective. In the present study, the participants were requested to self-administer fluticasone furoate with two sprays in each nostril for the first week to initiate the treatment effect. This one-week regular fluticasone furoate use might have caused the as-needed group to have more improvement in nasal symptoms than expected, as opposed to as-needed use for the entire six weeks.

The sensitivity analysis of the TNSS differences was done from the second week to the sixth week by utilizing the TNSS score on the seventh day as a baseline as this period was the real “entirely as-needed” and “entirely regular” comparison.

Compared to the as-needed group, the regular group had a greater mean alteration in TNSS in the sixth week. Both groups had substantial improvements in TNSS, individual nasal symptom score, NPIF, and RCQ-36 score from baseline to the sixth week. The NPIF, TNSS, and RCQ-36 scores in the regular group progressively got better with the maximum benefit witnessed in the fourth week. The study results, therefore, supported the regular use of fluticasone furoate for at least four weeks to obtain maximum clinical efficacy.

During the study, a discrepancy of improvement was noted between subjective nasal congestion score and NPIF. The difference in mean alteration of NPIF between the two groups began to be vital in the third week. This effect was sustained through the sixth week. In contrast, the difference in mean alteration of nasal congestion score between the two groups was marginally significant only in the sixth week.

In patients having moderate-to-severe perennial allergic rhinitis, intranasal corticosteroid monotherapy is advocated as the first-line treatment. Compared to intranasal corticosteroids, oral H1- antihistamines are known to have less potency and may not be appropriate for perennial allergic rhinitis patients who tend to have year-round symptoms.

The MASK study depicted that compared to oral H1-antihistamine, the intranasal corticosteroids-containing medications offer better improvement. However, most patients use intranasal corticosteroids only when their symptoms are suboptimally controlled and do not follow clinicians’ prescriptions.

Despite intranasal corticosteroids being generally well tolerated, they can have adverse effects such as epistaxis, nasal irritation, and potential growth-suppressive effect in children and adolescents.

This study showed that as-needed use improved TNSS, NPIF, and quality of life with less corticosteroid exposure compared to the regular regimen.

In conclusion, in patients with moderate-to-severe perennial allergic rhinitis, the as-needed intranasal corticosteroids use, at half of intranasal corticosteroids exposure, was comparable to regular use with regard to the improvement of nasal symptoms and quality of life from baseline to the sixth week. However, its effect was probably less sustained in alleviating symptoms. Although regular use of intranasal corticosteroids is suggested for managing perennial allergic rhinitis, the as-needed use of intranasal corticosteroids could be considered as a promising alternative regimen.