Introduction

Top Abstract Introduction Participants and methods Results Discussion References

Allergic rhinitis, whether seasonal or perennial, is characterised by sneezing, rhinorrhoea, obstruction of the nasal passages, conjunctival and pharyngeal itching, and lacrimation. Allergic rhinitis, often inappropriately called hay fever, is caused by the deposition of allergens (often pollen) on the nasal mucous membranes, resulting in a type I hypersensitivity reaction. ^{1 2}

Butterbur (Petasites hybridus; butter dock, bog rhubarb, exwort) is an Asteraceae herbaceous plant native to Europe, northern Africa, and south western Asia.³ The leaves and roots of butterbur contain a mixture of eremophilan type sesquiterpenes (petasines). Extracts of butterbur have been used in bronchial asthma, smooth muscle spasms, and headache.⁴ Petasines inhibit the biosynthesis of leukotrienes, which may be associated with antispasmodic activity and anti-inflammatory action in type I hypersensitivity.^5-7

The usual treatment for seasonal allergic rhinitis is antihistamines. These reduce rhinorrhoea and sneezing but are less effective for nasal congestion and may cause sedation and drowsiness. Antihistamines can be obtained over the counter for treatment of hay fever, and all may interact with alcohol and decrease driving ability.⁸ We conducted a randomised controlled trial of butterbur extract tablets (ZE 339) and a commonly used non-sedating antihistamine (cetirizine) to compare the effectiveness of these two treatments.

	Participants and methods

Top Abstract Introduction Participants and methods Results Discussion References

All participants were outpatients attending four general medicine and allergy clinics between June 1999 and June 2000. Study medication consisted of butterbur (petasites carbon dioxide extract ZE 339 standardised to 8.0mg of total petasine per tablet; one tablet, four times daily) or cetirizine (one 10 mg tablet daily), as recommended by the manufacturers. Each day, participants took five tablets, four of which contained either placebo or butterbur, and one contained either cetirizine or placebo, depending on the treatment group. The study was approved by the relevant ethics committees in Germany and Switzerland.

Participants
All participants were aged 18 years, had a history of seasonal allergic rhinitis for at least two consecutive years, and fulfilled the seasonal allergic rhinitis diagnostic criteria. Baseline assessment was made at the referral consultation, when the inclusion and exclusion criteria were checked. All participants had skin allergy tests, and all but one were allergic to pollen. They also had a full medical examination, after which they were given treatment for two weeks. Participants could return after one week if they experienced adverse events or deterioration. At the visit at the end of week 2, participants had a full medical examination and we checked compliance and adverse events. Exposure to pollen was confirmed for each participant through crosschecking the treatment period with the online regional pollen count service (www.pollenallergie.de).

Statistics, assignment, and analysis
Randomisation was provided centrally in blocks of four. Analysis was on an intention to treat basis, defined as all randomised patients who had at least one baseline and one follow up value and took any medication. The planned sample size was a minimum of 120 patients, based on previous studies of allergic rhinitis, ^{9 10} with a 10% expected withdrawal rate and an assumed effect size of 0.5.

The main outcome variable was change from baseline to end point in the score of each item on the medical outcome health survey questionnaire (SF-36).¹⁰ The secondary outcome variables were the physicians' clinical global impression score and the SF-36 score for overall status.¹¹

Between treatment comparisons were tested by the Mann-Whitney test (two sided). The exploratory secondary variables were evaluated by inference statistics with a shifted null hypothesis adjustment to baseline according to the method of Abt,¹² with means, standard deviation, medians, 95% confidence intervals, and absolute and relative frequencies. For participants who withdrew we carried forward the last observation. The mean of both treatment groups was used to substitute missing values.

	Results

Top Abstract Introduction Participants and methods Results Discussion References

Patients' characteristics and flow through study
A total of 131 patients were initially screened; six did not give consent, and 125 were randomised. Participants' characteristics at entry were similar in the two groups (table 1). The population was representative of patients with seasonal allergic rhinitis who seek treatment in the primary care sector

Efficacy results
At the end of the treatment period none of the scores in the butterbur group was more than 10% worse than in the cetirizine group (table 2). The secondary outcome measures were also comparable in the two treatment groups.

Safety results
The overall incidence of adverse events was similar for the two treatments: 16% in the butterbur group (10/61) and 17% in the cetirizine group (11/64). No event could be considered to be typically associated with butterbur, all having been reported once or twice only. Conversely, two thirds of events in the cetirizine group were typical of antihistaminesthat is, drowsiness and fatigue. One patient was withdrawn (butterbur group) because she required corticosteroids for previously existing asthma.

	Discussion

Top Abstract Introduction Participants and methods Results Discussion References

Although seasonal allergic rhinitis is common, methodologically robust studies are difficult to conduct, not least because of the easy access to anti-allergic treatments by patients. These treatments include a large number of antihistamines and corticosteroid nasal sprays available without prescription. To overcome the possible contamination of results by the use of other treatments, we monitored patients closely and allowed them to visit the clinics whenever they felt their condition needed further intervention. To enhance patient compliance, and bearing in mind the acutely debilitating symptoms of hay fever, we also kept the treatment period as short as possible (two weeks). In our experience, patients with this condition do not tolerate ineffective treatments for longer periods.

The number of randomised controlled trials with herbal medicines has increased substantially recently.^13-15 Herbal treatments are being used more often by doctors and, in our experience, are often requested by patients.

Value of butterbur
Although the effects of butterbur have been linked to its constituents,^5-7 we set out to test whether its clinical effects in seasonal allergic rhinitis were comparable to those of antihistamines as judged separately and blindly by patients and their doctors. The results showed that the effects of the two treatments are similar. The trends in favour of butterbur in some measures need to be confirmed in future prospective trials. With regard to safety, butterbur was well tolerated and did not have the sedative effects associated with antihistamines. We believe butterbur should be considered for treating seasonal allergic rhinitis, particularly in cases where the sedative effects of antihistamines need to be avoided.