Oliver Pfaar Centre for Rhinology and Allergology, Department of Otorhinolaryngology, University Hospital Mannheim , Ludger Klimek Centre for Rhinology and Allergology, Department of Otorhinolaryngology, University Hospital Mannheim

Originally printed in:
» European Respiratory Disease 2007 - Issue II

Approximately 10–40% of the worldwide population is affected by allergic rhinitis (AR). It has become increasingly common over the last few decades^1,2 and is now the most prevalent chronic disorder requiring treatment. Rhinorrhoea, sneezing, nasal congestion, an itchy nose and/or conjunctivitis are symptoms of the disease. Furthermore, co-morbid diseases such as allergic asthma, otitis media, chronic sinusitis and lower respiratory tract infections are common.³ AR influences cognitive function, resulting in impaired function at work or school and disrupted sleep patterns.² These effects mean the disease has an impact on healthrelated quality of life (HRQL).^4,5 Based on the time of allergic exposure, AR has traditionally been split into seasonal (SAR) and perennial (PAR) manifestations.² This definition does not entirely reflect patterns of AR symptoms in patients. For example, many patients with PAR do not show symptoms throughout the year. In light of this, the Allergic Rhinitis and its Impact on Asthma (ARIA) workshop group has developed a new classification of AR based on the duration of symptoms.⁶ Intermittent allergic rhinitis (IAR) is defined by the occurrence of AR symptoms for less than four days or less than four weeks a year, whereas persistent allergic rhinitis (PER) is defined by the occurrence of AR symptoms for more than four days or at least four consecutive weeks a year.

Management of the disease involves allergen avoidance, specific immunotherapy and controlling symptoms with pharmacotherapy. The first-line treatment for symptom-reduction is administration of H₁ receptor antagonists.⁷ Levocetirizine is a selective, potent, oral antihistamine H₁ receptor antagonist of the latest generation that is licensed for the symptomatic treatment of both SAR and PAR.⁸ The therapeutic efficacy of oral levocetirizine has been calculated in several clinical studies in patients with SAR, PAR and PER.⁹ This article reviews current literature on levocetirizine, although some data are available only as abstracts and/or poster presentations.

Levocetirizine in the Treatment of Seasonal Allergic Rhinitis

Both levocetirizine and cetirizine significantly attenuated the histamine-induced increase in nasal airway resistance by nearly 50%¹⁰ and caused a marked inhibition of histamine-induced wheal and flare, while levocetirizine 2.5mg had comparable antihistaminic activity to cetirizine 5mg.¹¹ Several studies on both adult and child SAR patients with oral levocetirizine in two- to six-week trials suggested that levocetirizine is an effective agent.^12–15

In a large German study in a primary care setting, oral levocetirizine 5mg once daily for 32 days was reported effective in treating patients with SAR and PAR with or without concurrent asthma (n=14,319) (see Table 1).¹⁴ Alleviation or improvement of symptoms (e.g. rhinorrhoea, sneezing, conjunctivitis and asthmatic symptoms) was observed in over 80% of patients after treatment. Global assessments also indicated good or very good efficacy in over 80%. Adverse effects were minimal.¹⁴ In a four-week non-comparative study of primary care centres in Belgium, these data were confirmed.¹⁵ In addition, the same authors analysed a subgroup of levocetirizine-treated patients and observed that the degree of pollen load did not have any influence on the efficacy. In one study of 470 patients, symptom severity scores for sneezing, rhinorrhoea, itchy nose and eyes were significantly decreased for all doses of levocetirizine, with 5mg once daily showing an optimal risk/benefit ratio in the treatment of SAR.¹⁶

In large, double-blind, multicentre trials in both adults and children, levocetirizine revealed significant therapeutic efficacy compared with placebo in terms of adjusted mean Total 4-Symptoms Scores (T4SS) as the primary end-point over a two-week interval.^13,17 In adults, levocetirizine 2.5–10mg once daily exposed a linear dose–response effect relative to placebo (p=0.0001), with all dosages more effective than placebo.¹⁷ Levocetirizine 5mg once daily showed improvement of T4SS from baseline by <50% relative to placebo under all weather conditions. However, an improvement of at least 50% (co-primary efficacy endpoint) could not be revealed. Interestingly, this end-point was met under dry weather conditions. The authors discussed the possibility that rainfall itself may decrease allergic symptoms in AR patients and consequently reduce the need for medication.¹⁷ In contrast, a T4SS reduction >50% could be shown in a study on paediatric patients after two weeks of therapy.¹³ In addition, in this study levocetirizine was seen to cause significant improvements of other secondary end-points such as sneezing, rhinorrhoea and pruritus. HRQL was also increased in the treatment of children. Individual domain scores such as nasal symptoms, ocular symptoms and practical problems showed significant improvements after a two-week therapy interval; however, the overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) scores increased from baseline by 34% in the levocetirizine-treated group. In addition, the clinical efficacy of levocetirizine was evaluated for symptoms of SAR in vivo in the environmental exposure unit (EEU).¹⁸

Levocetirizine in the Treatment of Perennial Allergic Rhinitis

Several short-term, randomised, double-blind trials have been performed with levocetirizine at a dose of 5mg daily for the treatment of PAR in child, adolescent and adult outpatients in the primary care setting.^19–21 In a randomised, double-blind, eight-week study, 294 PAR patients were treated with either levocetirizine 5mg or placebo once daily.²⁰ An improvement of the T4SS ≥50% compared with baseline with significant difference from placebo could be demonstrated after only one week of therapy with levocetirizine. Furthermore, the reduction of the adjusted mean symptoms score of rhinorrhoea, sneezing, nasal and ocular pruritus and nasal congestion compared with baseline was revealed to be significantly higher than placebo after one week of therapy (p≤0.008). The relative improvement for nasal congestion versus placebo reached 154% in favour of levocetirizine (p=0.002) after only one week of treatment. This was the best relative improvement among all the individual symptoms. Interestingly, the beneficial effect on nasal congestion was maintained throughout the entire study period, with a difference versus placebo reaching even higher statistical significance (p<0.001) over the four-week and sixweek periods. In a similar methodical setting an even higher improvement in symptoms (p≤0.0001) was seen after a 30-day course of treatment.²¹

Similar results were found in the treatment of children.²² In a placebocontrolled study of 306 children with PAR, a significant improvement of T4SS was shown. As secondary end-points, both the overall PRQLQ score (p≤0.05) and the individual domain scores (p<0.001) were significantly greater after two weeks of therapy with levocetirizine. In a study with the Vienna challenge chamber, patients sensitised to dust mites underwent a two-day allergen challenge and revealed an improvement of the complex symptom score (CSS) compared with baseline after only four hours.²³