Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma.

BACKGROUND: The treatment of allergic asthma by specific immunotherapy (SIT) is hampered by potential side-effects. OBJECTIVE: The aim of this study was to study the effect of omalizumab, a monoclonal anti-IgE antibody, in combination with SIT in patients with seasonal allergic rhinoconjunctivitis (SAR) and co-morbid seasonal allergic asthma (SAA) incompletely controlled by conventional pharmacotherapy. METHODS: A randomized, double-blind, placebo-controlled, multi-centre trial was performed to assess the efficacy and safety of omalizumab (Xolair) vs. placebo in combination with depigmented SIT (Depigoid) during the grass pollen season. Omalizumab or placebo was started 2 weeks before SIT; the whole treatment lasted 18 weeks. Primary endpoint was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use. RESULTS: A total of 140 patients (age 11-46 years) were randomized; and a total of 130 finished the study. Combination therapy reduced the symptom load by 39% (P=0.0464, Wilcoxon test) over SIT monotherapy. This difference was mainly due to reduced symptom severity (P=0.0044), while rescue medication use did not change significantly. Combination therapy also improved asthma control (Asthma Control Questionnaire, P=0.0295) and quality of life in the case of asthma (Asthma Quality of Life Questionnaire, P=0.0293) and rhinoconjunctivitis (Rhinoconjunctivitis Quality of Life Questionnaire, P=0.0537). Numbers of patients with 'excellent or good' treatment efficacy according to ratings of investigators (75.0% vs. 36.9%) or patients (78.5% vs. 46.1%) were markedly higher in the combination group than under SIT alone. CONCLUSION: Combination of omalizumab with SIT for treatment of patients with SAR and co-morbid SAA was safe and reduced the symptom load in a statistically significant and clinically meaningful manner.

Enhanced resistance to Sendai virus infection in DBA/2J mice with a botanical drug combination (Sinupret).

It was investigated whether the botanical drug combination Sinupret is able to modulate the resistance of mice to a respiratory tract infection with Sendai virus (Parainfluenza viridae) if given prophylactically to the animals. Three doses of Sinupret drops (SD) and Sinupret tablets (ST, p.o.), and two active controls, the chemical secretolytic ambroxol (p.o.) and the immunomodulator Muramyldipeptide (MDP, i.v.) were used. Test and reference substances were applied at days - 3 and -1 before infection, except MDP, which was given once on day--before infection. CD4+ and CD8 + lymphocyte subpopulations were measured after infection as indicators of immunological treatment response. Groups of 20 mice each were infected by intranasal application of Sendai virus under anaesthesia. We found that the 1 x and 5 x human doses of Sinupret drops significantly prolonged the survival times (p < 0.05) compared to placebo. Additionally, ambroxol and MDP were comparably less effective. In all groups, changes in CD4 + and CD8 + T-lymphocyte subpopulations of the peripheral blood were observed, but no clear relationship to the treatment results was seen. It was concluded that Sinupret increases the resistance to an experimentally induced respiratory tract infection in mice. Moreover, the effect of Sinupret was superior to that of an immunostimulant (MDP) and of a synthetic secretagogue (ambroxolhydrochloride).

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.

In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p=0.018; p=0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p=0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

A controlled multi-centre study of herbal versus synthetic secretolytic drugs for acute bronchitis.

Herbal expectorants and secretolytic drugs hold a sizeable share of the European market. Therefore it is essential to test their clinical effectiveness and safety. The aim of the present study was to compare the herbal medication Bronchipret(®) with various other pharmacotherapeutical options for acute bronchitis. The study was designed as a matched-pair comparison of 7783 patients. Clinical outcomes of bronchitis and adverse reactions were documented. The data were evaluated by comparing the treatment success of the test medication and 3 control groups using ordinal regression. The results suggest that clinical effectiveness of Bronchipret(®) was not less than with synthetic drugs. There was a tendency for better results with Bronchipret(®), particularly in the treatment of adults. Similar results were obtained with respect to adverse reactions. Particularly in the adult sub-group, these were markedly less with herbals as compared to synthetic drugs. These findings imply that a risk/benefit evaluation would favour Bronchipret(®) over synthetic drugs for acute bronchitis. Their interpretation is limited through the fact that this study could not be randomised nor blinded. The results therefore require confirmation through randomised, double-blind trials.

The effects of a special Agnus castus extract (BP1095E1) on prolactin secretion in healthy male subjects.

The effects of three doses of a special Agnus castus extract (BP1095E1)--extracts from 120 mg, 240 mg and 480 mg of drug per day--were examined within the framework of a placebo-controlled clinical study of tolerance and prolactin secretion in 20 healthy male subjects during a period of 14 days. There was good tolerance during the study as regards the following: adverse effects, the effects on blood pressure and heart rate, blood count, Quick's test, clinical chemistry as well as testosterone, FSH and LH values. During each study phase the 24-hour prolactin secretion profile was measured from the penultimate to the final day, and the amount of prolactin release was monitored an hour after TRH stimulation on the last day. A significant increase in the 24-hour profile was registered with the lowest dose in comparison to placebo, the opposite being the case with the higher doses, i.e. a slight reduction. In contrast to the administration of placebo, the 1-hour AUC after TRH stimulation resulted in a significant increase with the lowest dose and a significant reduction with the highest dose. The results suggest effects of the special Agnus castus extract which are dependent on the dose administered and the initial level of prolactin concentration.

[Comparison of the bioavailability of beta-aescin after single oral administration of two different drug formulations containing an extract of horse-chestnut seeds]. / Vergleichende Untersuchung zur Bioverfügbarkeit von beta-Aescin nach oraler Einmalverabreichung zweier Rosskastaniensamenextrakt enthaltender, galenisch unterschiedlicher Darreichungsformen.

The relative oral bioavailability of beta-escine (CAS 11072-93-8) from a sugar-coated tablet formulation was compared to a reference preparation available in capsule form in 18 healthy, male volunteers over a 48 h period. The study design was randomized, single-blind and cross-over. Both the test and the reference preparation contained 50 mg standardized horse chestnut seed extract; beta-escine was taken as the reference substance. By means of a newly developed, validated radioimmunosorbent assay (RIA), beta-escine in plasma was determined (blind samples) after oral intake of a single dose of each drug formulation. The confidence limits calculated for the AUC, Cmax and Tmax of the test preparation exceed the upper limit of the specified equivalence range of 80%--125%, but do never fall below the lower limit. Therefore, bioin-equivalence cannot be rejected statistically. All the bioavailability data for the test preparation--measured with the newly developed RIA--exceed the corresponding values for the reference preparation. As the rate of absorption of aesculetinic triterpene glycosides is low, the higher bioavailability of the test preparation is desirable from a therapeutical point of view. Since the reference preparation is classified as being clinically effective, the test preparation must also be estimated as being clinically effective. Adverse drug effects were not observed with either the test preparation or the reference preparation.

Adverse drug reactions to herbal and synthetic expectorants.

Our knowledge relating to adverse drug reactions (ADRs) of phytomedicines is highly fragmentary. The aim of this study was to define the prevalence of ADRs following medication with herbal or synthetic expectorants. In a multicentre, comparative post-marketing surveillance study of more than 3000 patients with acute bronchitis, about half were treated with a herbal remedy (SinupretR) and the other half with various other expectorants. In ascending order of incidence, ADRs were noted during mono-medication of SinupretR (0.8%), Ambroxol (1.0%) and acetylcysteine (4.3%). When concomitant drugs were used, this rank order was unchanged but incidence rates were markedly increased (3.4, 6.5 and 8.2%, respectively). The most frequent ADRs were gastrointestinal symptoms. It is concluded that expectorants are associated with ADRs in roughly 1-5% of cases undergoing single drug treatment and in 3-10% when more than one medication is being used. Amongst the expectorants used in this study, the herbal preparation SinupretR is associated with the lowest incidence of ADRs.