The Treatment Of Allergic Rhinitis Disease

Published Date: 02 Nov 2017

Rhinitis is a condition which is defined when there is a presence of at least one of the following symptoms; nasal congestion, rhinorrhoea, nasal itching, nasal obstruction or sneezing. The condition is classified into two main groups; allergic rhinitis and non-allergic rhinitis (1). As part of this essay I will be focusing on allergic rhinitis and this occurs when nasal symptoms are triggered by an allergen. Thus, one way of treating allergic rhinitis is allergen avoidance (1, 2). In addition, drugs such as antihistamine, corticosteroids, intranasal cromones and leukotriene receptor antagonists are used and where drug therapy fails to be effective immunotherapy is sometimes used (2, 3).

Fluticasone propionate which will be the focus of my essay is from the corticosteroid class of medication for allergic rhinitis and is available in the spray form.

Background of the drug

The drug substance of fluticasone propionate was discovered in 1981 by a pharmaceutical company; GlaxoSmithKline (4, 5) and has a crystal structure with the formula C25H31F3O5S.

Fluticasone propionate is an anti-allergic and anti-inflammatory corticosteroid used to treat various types of inflammation namely occurring in the following conditions;

File:Fluticasone propionate.svg

Asthma

Seasonal allergic rhinitis

Perennial rhinitis

Nasal polyps

Symptoms of nasal obstruction

Dermatitis

Eczema

Psoriasis

Insect bites

Chronic obstructive pulmonary disease

Fluticasone propionate is approved worldwide for respiratory use through either a dry powder inhaler (Rotadisk®), a nasal spray (Flonase®) or a metered dose inhaler (Flovent®) (4) and Fluticasone propionate is available under the following brand names;

Flixotide Evohaler, Flixotide Accuhaler, Flixonase, Nasofan, Flixonase Nasule, Cutivate

In regards to specific products containing fluticasone available in the market are the following:

AVAMYS 27.5 micrograms/spray, nasal spray suspension

Boots Pharmacy Hayfever and Allergy 50 microgram Nasal Spray

Boots Allergy Relief 50 Microgram Nasal Spray

Nasofan Allergy 50 microgram Nasal Spray

Cutivate Cream 0.05%.

Cutivate Ointment 0.005%

Flixonase Aqueous Nasal Spray

Flixonaseâ„¢ Nasuleâ„¢ Drops 400 micrograms (1 mg/ml), nasal drops suspension.

Flixonaseâ„¢ Nasuleâ„¢ Drops 400 micrograms (1 mg/ml), nasal drops suspension.

FlixotideTM 50 micrograms EvohalerTM

FlixotideTM 125 micrograms EvohalerTM

FlixotideTM 250 micrograms EvohalerTM

Flixotide Accuhaler 50 micrograms

Flixotide Accuhaler 100 micrograms

Flixotide Accuhaler 250 micrograms

Flixotide Accuhaler 500 micrograms

Flixotide Nebules 0.5mg/2ml

Flixotide Nebules 2mg/2ml

flutiform®▼50 microgram/5 microgram per actuation pressurised inhalation, suspensions.

flutiform®▼125 microgram/5 microgram per actuation pressurised inhalation, suspensions.

flutiform®▼250 microgram/10 microgram per actuation pressurised inhalation, suspensions.

Flixonase Allergy Nasal Spray

Pirinase Hayfever 0.05% Nasal Spray

Seretide Accuhaler 50 microgram /100 microgram /dose inhalation powder, pre-dispensed.

Seretide Accuhaler 50 microgram /250 microgram /dose inhalation powder, pre-dispensed.

Seretide Accuhaler 50 microgram /500 microgram /dose inhalation powder, pre-dispensed.

Seretide Evohaler 25 microgram /50 microgram/dose pressurised inhalation, suspension.

Seretide Evohaler 25 microgram /125 microgram/dose pressurised inhalation, suspension.

Seretide Evohaler 25 microgram /250 microgram/dose pressurised inhalation, suspension.

Efficacy of fluticasone propionate in treatment of allergic rhinitis:

In regards to the efficacy of Fluticasone propionate for the treatment of allergic rhinitis many studies have been carried out. One double-masked parallel-group study carried out confirmed that the efficacy of fluticasone propionate nasal spray is due to the topical effect rather than systemic effect (6). In this study 304 patients with allergic rhinitis were randomly assigned to either the nasal spray, oral form of the medication or placebo. Symptoms of allergic rhinitis were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate group or the placebo group. Interestingly, there was very little difference in the symptoms of the placebo group and the oral fluticasone propionate group further indicating the efficacy of fluticasone propionate to be directly dependent on the topical effect.

A meta-analysis (7) study where efficacy data from seven multi-centre, randomised, double-blind, placebo- controlled studies was pooled and the results showed that intranasal corticosteroid in the form of fluticasone propionate decreased ocular and nasal symptoms associated with allergic rhinitis. Each one of the seven studies included in this meta-analysis evaluated the efficacy of intranasal fluticasone propionate 200 micrograms given once daily, the symptomology was assessed after 7 and 14 days of treatment. I believe a shortcoming of the studies included in this meta-analysis was that a visual analogue scale of 0-100 was used and thus it is very subjective and prone to bias. However as the p-value for the results is <0.001 so we can’t say that the beneficial effect of fluticasone propionate evident from studies to be attributed to chance. The improvement was noticed in ocular and nasal symptoms and a difference of 25 points in the mean change from baseline was considered clinically significant. Group that took fluticasone propionate had greater mean changes from baseline compared with placebo. The mean decreases from baseline in symptoms at day 7 were 76.0 points for the fluticasone propionate group and 50.9 points for the placebo group (p < 0.001), a difference between groups of 25.1. Furthermore, at day 14, mean decreases from baseline was 91.8 points for the fluticasone propionate group and 60.2 points for the placebo group (p < 0.001), a difference between groups of 31.6. In conclusion, this meta-analysis suggests that fluticasone propionate is not only effective at reducing nasal symptoms but also ocular symptoms such as tearing experienced by patients with allergic rhinitis.

The effectiveness of fluticasone propionate at controlling ocular symptoms of allergic rhinitis has also been documented in other studies (8, 9, 10). In conclusion what I gathered from the results of this meta-analysis was that, based on a visual analogue score at 7 days there was only a 25.1 point reduction in symptoms of allergic rhinitis as majority of the symptoms were self-limiting thus relieved to an extent with or without treatment. At 14 days a greater difference in symptomology is noticed where fluticasone propionate eliminates symptoms by 31.6 points in comparison to placebo treatment. Thus the longer the treatment with the medication the better the results but at the same time this shows that the efficacy of the treatment is no immediate and requires time.

Comparison of other medicinal products used for allergic rhinitis

There are a few classes of drugs that are used to treat allergic rhinitis namely; Antihistamines, corticosteroids (mentioned above in the form of fluticasone propionate), leukotriene receptor antagonists, nasal decongestants and cromoglycate.

Histamine

The pathophysiology behind allergic rhinitis is dependent on histamine which is the major reason for the symptoms such as rhinorrhoea, nasal itching and sneezing however, the nasal congestion experienced in this condition is not due to histamine. Thus the use of anti-histamine class of medication seems logical and expected to relieve symptoms. Studies in this regard show that antihistamines are effective at relieving symptoms of allergic rhinitis by blocking the effects of histamine which is the major insulting agent in allergic rhinitis as mentioned above. Efficacy of fluticasone propionate in comparison to antihistamine was outlined in one meta-analysis study where a systematic review of randomised, controlled trials was performed to determine whether intranasal corticosteroids were advantageous over topical antihistamines in the treatment of allergic rhinitis (11). I think very highly of this meta-analysis as a vast source of data was used; studies obtained through searches on MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical companies, and references of included trials. Furthermore, the selection of studies was very well categorised by the following criteria;

published randomized controlled trials

single- or double-blind studies

Presence of one of the following clinical outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of life and side effects.

In total nine studies (12, 13, 14, 15) which meant 648 patients with allergic rhinitis were selected and results showed that intranasal corticosteroids gave a significantly greater reduction of nasal symptoms (standardized mean difference −0.36, 95% confidence interval −0.57 to −0.14). The results were further grouped to define the change in particular symptoms so that we can deduce that sneezing had a standardized mean difference of −0.41 where the 95% confidence interval was −0.57 to −0.24), rhinorrhoea (standardised mean difference −0.47, and 95% confidence interval of−0.64 to −0.29), itching (standardised mean difference −0.38, 95% confidence interval of −0.56 to −0.19), and nasal blockage ( standardised mean difference of −0.86 and 95% confidence interval being −1.07 to −0.64) in comparison to topical antihistamines.

The study further concluded no significant difference in the ocular symptoms as standardised mean difference in two groups was -0.07 and the 95% confidence interval being -0.26 to 0.12. Thus in summary intranasal corticosteroids produced greater relief of nasal symptoms compared to topical antihistamines however; the difference was restricted to nasal symptoms and was not reproduced in regards to ocular symptoms associated with allergic rhinitis.

This class of medication can be bought over the counter however; the nasal spray form of antihistamine is only available with a prescription.

Leukotriene receptor antagonists

Leukotriene receptor antagonists are another class of medication used in allergic rhinitis. Similar to histamine, leukotriene is also a pro-inflammotory mediator in allergic rhinitis but the receptors through which their actions are mediated are specific for each chemical. As a result, leukotrienes in contrast to histamine result in nasal airway resistance and vascular permeability.

Montelukast and zafirlukast are examples of leukotriene receptor antagonists and have shown to be effective in the treatment of allergic rhinitis but studies (16, 17, 18) however show them to not to be as effective as intranasal corticosteroids.

Combination therapy with leukotriene receptor antagonists and antihistamines was shown to be as effective as intranasal corticosteroids (19) however; this finding was not supported by later and longer-term studies (21, 21) which found intranasal steroids to be more effective than the combination therapy. I think this is a very important point which should be noted as mentioned earlier, published literature on efficacy of fluticasone propionate suggested that it takes a longer time (14 days) for the benefit of fluticasone propionate to be noticed. Therefore, even though combination therapy with anti-histamines and leukotriene may seem more efficacious the benefits are short lived and not as striking as the benefits of fluticasone propionate in the long term.

In summary leukotriene receptors antagonists should be considered when oral antihistamines and or intranasal corticosteroids are not tolerated by the patient or they are not effective in controlling the symptoms of allergic rhinitis. As a last resort when pharmacological therapy with oral antihistamines, intranasal corticosteroids and leukotriene receptor antagonists is not effective or is not tolerated, then allergen immunotherapy should be considered (22, 23, 27, 29).

Nasal decongestants

At times, oral and intranasal decongestant namely; pseudoephedrine and phenylephrine are used to relieve nasal congestion in allergic rhinitis. But studies (24, 25, 26, 28) prove this class of medication to be not very useful due to its side-effects and contraindications in patients who have uncontrolled hypertension and severe coronary artery disease. Furthermore, prolonged use of intranasal decongestants carries the risk of developing rebound nasal congestion.

Cromones

Sodium cromoglycate has also been shown to reduce rhinorrhoea, sneezing and nasal itching but due to the poor efficacy of the drug in allergic rhinitis it is not widely used. (25, 28)

Advantages and disadvantages of fluticasone propionate to other medicinal products

Fluticasone propionate is not only the most efficacious medication for allergic rhinitis but it also has the least side effects in comparison to other drugs used for the condition. The common side effects of Fluticasone propionate are nasal irritation and stinging which can both be prevented if the spray is aimed slightly away from the nasal septum (24). In comparison to the side effects of other medications, these side effects seem least adverse in nature and not only are they preventable but they also cause no hindrance in the patient’s lifestyle. I say this in regards to the side effects of antihistamines, sedation being the most common thus, patients are advised not to use machinery or drive after taking anti-histamines. Furthermore, fluticasone propionate relieves ocular symptoms experienced in allergic rhinitis as well as the nasal symptoms and this is one mechanism that is unique to intra nasal corticosteroids not seen in any of the other medication classes for allergic rhinitis (6, 7). Another advantage of using fluticasone propionate is that it is available in generic form which means it costs less and given the current financial situation of the NHS, the lower cost of a medication can sometimes aid decision making during prescribing. However, in regards to fluticasone propionate use for allergic rhinitis the cost will be one of the less important reasons for prescribing as it is the most efficacious medication for the condition and the cost will be an extra benefit of treatment with this medication. Furthermore, it may sound like an obvious reason but nevertheless, I view it as an important advantage that fluticasone propionate is approved by the Food and Drug Administration to treat allergic rhinitis. Sometimes studies show a medication to be beneficial for certain conditions but it is not in fact approved to be used in that condition and this reason can deter physicians to prescribe it and also puts pharmacists in a difficult position as they have a duty of checking prescriptions and making sure there are no contraindications.

In regards to the disadvantages of fluticasone propionate it will only be the side effects of nasal irritation and stinging. The nasal form of the medication further reduces the negative effects seen with systemic corticosteroids and not only that but in allergic rhinitis studies have shown that only the nasal spray form of the medication is beneficial in relieving symptoms (6). Flowery smell is another disadvantage for some people who dislike its smell.

Analysis of the market potential for the development of new drug candidates to treat allergic rhinitis

In order to decide whether a market potential exists for the development of a new drug to treat allergic rhinitis certain points need to be researched. I would begin by looking at the epidemiology of the condition i.e. the number of individuals affected by the condition and the duration for which the condition lasts in individuals; short-term or a chronic condition. I would then move onto research the medications already available on the market for the treatment of allergic rhinitis and follow this up by looking at the studies which show the efficacy of the medications. My decision of carrying out drug development will be largely based on the above points. Once I decide that there is a need to develop a drug for allergic rhinitis I would look at the funds available for it and whether these are able to meet the requirement of the project.

In regards to the treatment of allergic rhinitis I feel that there is a potential for the development of a new drug and I say this based on the studies I have read which show the lack of efficacy of treatment already available on the market. Out of the different classes of medications available, fluticasone propionate was the one that was most efficacious with the least side effects but even with this treatment patients were not completely relieved of their symptoms. The meta-analysis (7) that looked at the efficacy of fluticasone propionate showed that there was an average reduction of symptoms by 90%, in other words 10% of symptoms were still present despite using the best medication available for the condition. Having said that, at this point I would like to further research the market and ask the patients suffering from allergic rhinitis whether they are satisfied with the 90% reduction in symptoms or would they be prefer something that was 100% efficacious. In my opinion the answer would be that they would like something that completely resolved their symptoms and hence, I would like to know what kind of side effects if any are they able to tolerate in order to get the 100% resolution of symptoms. I believe the side effects to be an important consideration for drug development as there are very few drugs available that have no side effects if any. Side effects are one reason why many patients prefer not to take any medication and tolerate the symptoms caused by the particular illness.

Fluticasone propionate is a very effective medication for allergic rhinitis with minimal side-effects and thus strikes a very good balance in treating allergic rhinitis. Furthermore, given the nature of the condition it may be possible to take forward the idea of immunotherapy so that individuals are made immune to the allergy and therefore, overcome their condition.

In conclusion the only short coming of existing treatment would be that it is only 90% effective and that it has minor side effect of nasal irritation. I don’t believe that these points are significant enough to embark on further drug development as it is an expensive process and the chances of coming up with something that is 100% effective in relieving the nasal symptoms as well as ocular symptoms of allergic rhinitis are minute.