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Herbal medicines like Esberitox (TOX, wild indigo root stock, echinacea root, thuja tips and leaves) are used to treat common colds. Several randomized, controlled trials (RCT) document the efficacy and safety of TOX in this indication. So far its efficacy and safety has not been evaluated meta-analytically. We included individual patient data from all 825 patients from 3 RCTs. 693 patients had been treated with TOX, 132 with placebo (PLA) (7-9 days). All symptom scores were adjusted to baseline and meta-analyzed regarding area under the curve (AUC), time to response (≥50% decrease of symptom score), response rate and duration of the cold. The AUCs of the rhinitis score were 19.05 with TOX superior to 20.57 with PLA (p=0.020), bronchitis score 14.92 versus 16.16 (p=0.039) and well-being 208.4 versus 216.4 (p=0.008). Response rates were higher in TOX than PLA in all scores. The times to response showed an acceleration of the healing process of rhinitis (1.5 days, p=0.049), bronchitis (2 days) and pain (2 days, p=0.008). The duration of the cold was shortened by TOX by up to 2.3 days. The ADR-rate did not differ significantly (2.7% vs. 1.5%, p=0.41). Tolerability was good to very good in 98.4% (TOX) and 99.2% (PLA) (p=0.34). In conclusion, this meta-analysis confirmed the efficacy and tolerability of Esberitox at a higher level of evidence. It accelerates the improvement of cold symptoms by up to 2 days and shortens the duration of colds by up to 2.3 days.

Background: Brexpiprazole and aripiprazole are atypical antipsychotics that act as partial agonists at the dopamine D2 receptor. No head-to-head trial comparing brexpiprazole and aripiprazole in the treatment of schizophrenia is available. Here, we carry out a systematic review and comparison of the efficacy and safety of brexpiprazole and aripiprazole in schizophrenia treatment.Methods: We employed an indirect meta-analysis to determine effect sizes from randomised placebo-controlled trials with brexpiprazole and aripiprazole in the acute treatment of schizophrenia. We compared responder rates, incidences of adverse events and serious adverse events, the number needed to treat (NNT) for response, number needed to harm (NNH) for adverse events or treatment discontinuation, and likelihood to be helped or harmed (LHH) as efficacy and safety indices of the two drugs. Results: Five studies for each drug were included in the analysis. Similar risk differences vs. placebo were observed for responder rates under brexpiprazole (10.2%, p = 0.0015) and aripiprazole (10.3%, p = 0.0003). Higher incidences of adverse events and serious adverse events were seen under aripiprazole compared with brexpiprazole, however, the risk differences were not statistically significant. The NNT for response was 11 for both substances. For brexpiprazole compared with placebo, we did not find an increase of adverse events (NNH = 27, not significant), however, we found an increased number of adverse events for aripiprazole versus placebo (NNH = 17, p < 0.05). For both drugs, benefits were encountered more often than harms, with an LHH for any adverse event of 2.41 for brexpiprazole and 1.56 for aripiprazole, respectively. Conclusions: The likelihood to be helped rather than harmed was greater with brexpiprazole compared to aripiprazole for the total rate of adverse events (ratio of brexpiprazole LHH/aripiprazole LHH = 1.54).

Background For causal treatment by allergy immunotherapy (AIT) a single or few allergen products for the clinically most relevant allergens are applied to treat multiple allergies, but few data on the tolerability of multiple AIT applications are available. Objective The aim of our study was to investigate safety and tolerability in patients treated by subcutaneous immunotherapy (SCIT) and concomitant SCIT or sublingual immunotherapy (SLIT) products. Methods In a non-interventional, observational study in Germany treatment of patients with a primary SCIT and concomitant AIT (SCIT or SLIT) was documented during the first 4 months of treatment. Adverse events (AEs) were recorded by the physicians and by patients in diaries, and coded using the Medical Dictionary for Regulatory Activities (MedDRA). Results Three hundred and seven patients were treated with the primary SCIT by 79 allergists, and 271 received a concomitant AIT. AEs were reported in 92 (33.9%) patients and adverse drug reactions (ADRs) in 63 (23.2%) patients related to the primary SCIT and in 69 (25.5%) to the concomitant AIT; six (2.2%) patients discontinued due to ADRs. ADRs were mild or moderate in 40 (14.8%) patients, severe in 23 (8.5%), and serious in one patient. The most frequent reactions were local swelling and pruritus. Overall tolerability was assessed as ‘good’ or ‘very good’ by 95.6% of patients and 96.7% of physicians. Conclusions Compared with data from a large previous study no increase in the frequency of ADRs in real life or change in the tolerability profile was observed for SCIT with concomitant SCIT or SLIT.

Hintergrund: In der vorliegenden Studie wurden die Wirksamkeit und Verträglichkeit des homöopathischen Arzneimittels Sinusitis Hevert SL an Patienten mit akuter Rhinosinusitis untersucht. Methoden: In einer randomisierten, placebokontrollierten klinischen Studie wurden 314 Patienten mit bis zu 3 Tagen bestehenden Symptomen, leichtem bis moderatem Gesichtsschmerz und einem Major Rhinosinusitis Symptom Score (MRSS) ≥ 8 und ≤ 14 für 15 Tage (Tag 0 erster Arztbesuch plus 14 Tage Behandlung) eingeschlossen und mit Sinusitis Hevert SL oder Placebo behandelt. Den primären Endpunkt bildeten die Responderrate im MRSS (Reduktion ≥ 50%) bei der Abschlussvisite sowie die Rate der Remissionen (komplettes Abklingen aller 5 Hauptsymptome). Sekundäre Zielkriterien bildeten die Einschätzung der Wirksamkeit durch den Prüfer (auf einer 4-Punkte-Skala) und der Sino-Nasal Outcome Test 20 German Adapted Version (SNOT-20 GAV; Selbsterhebung durch die Patienten). Ergebnisse: 314 Patienten wurden in die Studie eingeschlossen. Davon wurden 308 mit der Studienmedikation behandelt: 153 mit Sinusitis Hevert SL und 155 mit Placebo. 265 Patienten schlossen die Studie vollständig und valide ab (Valid Completers). Die MRSSpat-Responderrate aller Patienten war für Sinusitis Hevert SL nicht signifikant besser (85,6% vs. 80,6%; p = 0,243), die Rate der Remissionen war mit 31,4% für Sinusitis Hevert SL und 37,4% für Placebo in beiden Gruppen nicht signifikant unterschiedlich (p = 0,2641). In der sekundären Completer-Analyse zeigte sich eine signifikante Differenz der Responderraten von 92,1% versus 83,5% zugunsten von Sinusitis Hevert SL (p = 0,032). Weiter war die Zeit bis zur Verbesserung der Rhinorrhoe signifikant kürzer (4,0 vs. 6,0 Tage; p = 0,040). Vor allem relevante nasale Symptome des SNOT-20 und die Lebensqualität verbesserten sich unter Behandlung mit Sinusitis Hevert SL signifikant deutlicher. Schlussfolgerungen: Es zeigte sich in dieser Studie bei akuter Rhinosinusitis und hoher Placebo-Ansprechrate keine Überlegenheit für Sinusitis Hevert SL in der Gesamtresponder- und Remissionsrate. Es fand sich ein Nutzen von Sinusitis Hevert SL in der Auswertung der Valid Completers für die Response sowie für spezifische Verbesserungen klinisch relevanter Symptome und die Abheilungsgeschwindigkeit der akuten Rhinosinusitis bei guter Verträglichkeit.

Aims To verify the efficacy, safety and tolerability of intravesical administration of 0.1% oxybutynin hydrochloride compared to its oral administration for treatment of neurogenic detrusor overactivity (NDO) in a randomized, prospective, controlled, open-label, multi-center trial in 35 adult patients. Methods NDO was confirmed within the previous 24 months by urodynamic studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin hydrochloride orally three times per day for a period of 28 days. Primary efficacy criterion was the change in the maximum bladder capacity between the beginning of the study and after 4 weeks as assessed by UDS. Adverse drug reactions (ADR) were collected and an evaluation of anticholinergic effects was conducted. Results The increase in maximum bladder capacity was 117 ml with intravesical application (P = 0.0002) versus 18 ml with the oral application (P = 0.51). The difference was statistically significant (P = 0.0086). ADR were reported by 10 (55.6%) of patients with intravesical administration, and by 14 (82.4%) of patients with oral administration. Significant differences in favor of the intravesical application were observed in ADR affecting vision (1/10 vs. 9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14), and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were reported. Conclusions This study demonstrates the efficacy and safety of intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect to the increase in maximum bladder capacity. Neurourol. Urodynam. © 2015 Wiley Periodicals, Inc.

Introduction Selegiline and rasagiline are established in the treatment of Parkinson’s disease. As no direct comparative randomised controlled trials on these drugs are available, an indirect meta-analysis was conducted. Objective Goal of the meta-analysis was to examine the clinical differentiation between rasagiline and selegiline based on efficacy and safety in Parkinson’s disease. Methods Literature databases, study registries and references of relevant publications were the basis of our literature search. Studies were selected according to Jadad and Delphi criteria. The analysis used a fixed effects model based on standardised mean differences for efficacy criteria and risk differences of safety outcomes. As outcomes, UPDRS (primary) and UPDRS motor functions, mental and ADL, the Schwab and England scale, the off-time as well as safety as secondary outcomes were used. Results Rasagiline showed a statistically significant advantage in the primary endpoint UPDRS total scores (monotherapy: p = 0.048, sensitivity analysis: p = 0.023; pooled analyses: p = 0.043, sensitivity analysis p = 0.014) and the secondary endpoint UPDRS motor functions (monotherapy: p = 0.049, sensitivity analysis p = 0.031; pooled analyses: not significant, sensitivity analysis: p = 0.046). For the other secondary outcome parameters, a numerical advantage for rasagiline was found. Discontinuation rates due to adverse effects showed a tendency in favour of rasagiline. Risk for adverse events such as dizziness, hallucinations, diarrhoea and syncope were lower with rasagiline than selegiline (each p Conclusion This meta-analysis showed a statistically significant and clinically relevant advantage for rasagiline over selegiline in the primary endpoint. The superiority of rasagiline was further substantiated with advantages in tolerability and safety.

The aim of this ICH-GCP study was to investigate the efficacy and safety of a prophylactic administration of a combination herbal medicinal product (CHMP) in two dosages compared to placebo with respect to the incidence of new occurring infections of the respiratory tract (RTI). Clinical experience of prophylactic treatment of respiratory tract infections with the marketed CHMP containing horseradish root (Armoraciae rusticanae radix) and nasturtium (Tropaeoli majoris herba) has existed for decades.The study was performed as a phase III, multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group trial. All groups received two film coated tablets three times a day. Group 1 received the CHMP tablets 3 × 2 per day, group 2 the CHMP tablets 2 × 2 and placebo tablets 2 × 1 per day and group 3 received placebo tablets 3 × 2 per day. Maximum duration of treatment was 84 days. The primary efficacy criterion was the comparison of the incidences of new occurring RTIs between the treatment groups during the prophylactic treatment. In addition the character of occurring infections, number of sick days and severity of infections were compared. Further criteria were subjects' well being, the satisfaction of subjects with the respective treatments and severity and incidence of the observed adverse events (AE) and serious adverse events (SAE) during the study period.EudraCT No. 2010-023227-26.From 371 subjects screened, a total of 351 subjects of both sexes from 18 to 75 years were randomly allocated to one of the three groups. In order to achieve scientifically and medically impeccable results it was necessary to address acute infections of the respiratory tract occurring during the normal incubation period. Early infections (≤day 7) were excluded from the data set in a sensitivity analysis. In the intention to treat (ITT) population excluding early infections ≤day 7 (n = 344) the infection rates were 13.3% for CHMP 3 × 2 (n = 113), 18.4% for CHMP 2 × 2 (n = 114) and 25.6% for placebo (n = 117). The statistical trend test showed significant results (p = 0.0171). For the per protocol (PP) population - also excluding infections ≤day 7 (n = 334) - infection rates were: CHMP 3 × 2 (n = 110) 12.7%, CHMP 2 × 2 (n = 113) 18.6% and placebo (n = 111) 24.3% (p = 0.0266). Secondary parameters of infections (infection diagnosis, intensity, duration) showed no relevant differences between the treatment groups. The study medication was well tolerated.This was the first clinical ICH-GCP study with the CHMP conducted in this indication and with a sufficient number of subjects. The study population comprised subjects from 18 to 75 years and covered different diagnoses of RTIs. The results show a benefit when using 3 × 2 film tablets of CHMP for prophylaxis of RTIs. However, no data are available on use of the CHMP in this indication in children, adolescents and the elderly (over 75 years).This trial demonstrates the efficacy and safety of the combination herbal medicinal product as the treatment of first choice in the prophylactic treatment of episodes of respiratory tract infections. Clinical experience was confirmed in an ICH-GCP study.

Background: Complementary therapies are frequently used by patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the efficacy and safety of long-term therapy with a new Boswellia serrata extract (Boswelan, PS0201Bo) in maintaining remission in patients with Crohn's disease (CD). Methods: In 22 German centers a double-blind, placebo-controlled, randomized, parallel study was performed. In all, 108 outpatients with CD in clinical remission were included. Patients were randomized to Boswelan (3×2 capsules/day; 400 mg each) or placebo for 52 weeks. The primary endpoint was the proportion of patients in whom remission was maintained throughout the 52 weeks. Secondary endpoints were time to relapse, changes of Crohn's Disease Activity Index (CDAI), and IBD Questionnaire (IBDQ) scores. Results: The trial was prematurely terminated due to insufficient discrimination of drug and placebo with regard to the primary efficacy endpoint. A total of 82 patients were randomized to Boswelan (n = 42) or placebo (n = 40). Sixty-six patients could be analyzed for efficacy. 59.9% of the actively treated patients and 55.3% of the placebo group stayed in remission (P = 0.85). The mean time to diagnosis of relapse was 171 days for the active group and 185 days for the placebo group (P = 0.69). With respect to CDAI, IBDQ, and laboratory measurements of inflammation, no advantages in favor of active treatment were detected. Regarding safety concerns, no disadvantages of taking the drug compared to placebo were observed. Conclusions: The trial confirmed good tolerability of a new Boswellia serrata extract, Boswelan, in long-term treatment of CD. However, superiority versus placebo in maintenance therapy of remission could not be demonstrated. (Inflamm Bowel Dis 2011)

Background Oral allergy syndrome (OAS) triggered by fruit and vegetables often occurs in patients with pollen-induced rhinoconjunctivitis because of cross-reactive epitopes in pollen and associated foods. This open observational study examined the effect of pollen-specific sublingual immunotherapy ([SLIT] B. U. Pangramin or SLITone involving birch/alder/hazel, grasses/rye, and/or mugwort) on OAS triggered by several foods in patients treated in standard practice. Very few studies have examined SLIT use in this situation.Methods Patients (n = 102) had pollen-induced rhinoconjunctivitis and OAS and were followed for up to 12 months. Baseline OAS (triggers, symptoms, and symptom severity) was assessed by questionnaire and patient history. Change in OAS was assessed using oral challenge test with 1 or 2 dominant food triggers (and compared with the sum score calculated from the OAS questionnaire at baseline) and clinician ratings of change. Pollen-induced rhinoconjunctivitis symptoms and medication use were also measured.Results In the oral challenge test, 77.0% of patients were considered responders (decrease in sum score of ≥ 50%; no difference in patients receiving B. U. Pangramin or SLITone). At baseline, investigators rated OAS severity as at least moderate in 94.9% of patients compared with 36.9% after 12 months of treatment. After 12 months, OAS was rated as much or very much improved in 72.9% of patients. Sublingual immunotherapy significantly reduced rhinoconjunctivitis symptoms and medication use. Only 10% of patients experienced adverse drug reactions.Conclusion This study supplements the sparse literature on this topic and suggests that pollen-specific SLIT can reduce OAS triggered by pollen-associated foods in patients with pollen-induced rhinoconjunctivitis. Keywords: immunotherapy, oral allergy syndrome, pollen, rhinoconjunctivitis, sublingual

Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose–response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD ≥40 and allergic sensitization to house dust mites [CAP-FEIA ≥3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere–Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel–Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.

Background: For the immunotherapy of Hymenoptera venom allergy various preparations and treatment protocols are in use. However, controlled studies making direct comparisons of the efficacy and safety of different regimens are rare. Objective: To assess prospectively different venom immunotherapy (VIT) protocols using an aqueous or an aluminium hydroxide adsorbed allergen preparation for the treatment of honeybee venom (HBV) allergy. Methods: Sixty-five HBV allergic patients (42 males, 23 females; aged 17–75 years) with a history of systemic anaphylactic reactions (SARs) to honeybee stings were treated according to three different regimens. During the incremental phase, patients in group A (n = 21) or B (n = 21) received an aqueous preparation according to a rush protocol. Patients in group C (n = 23) were treated with conventional (‘slow’) VIT using an aluminium hydroxide adsorbed depot preparation. The maintenance dose was 100 μg venom in all groups. Maintenance treatment in group A was performed with the aqueous preparation administered every 4 weeks, whereas in groups B and C the depot preparation was administered every 8 weeks (group B) or every 4 weeks (group C). A sting challenge test with a living honeybee was performed in 49 patients, 6–12 months after reaching the maintenance dose. Another seven patients were stung accidentally by a honeybee (‘field sting’). Results: Treatment with the aqueous preparation evoked large local reactions more frequently than the depot preparation in the dose increase phase [53/693 (7.6%) vs 8/206 (3.9%); P = 0.059] and also in the course of maintenance therapy [85/172 (49.4%) vs 58/478 (12.1%); P

To verify the efficacy, safety and tolerability of intravesical administration of 0.1% oxybutynin hydrochloride compared to its oral administration for treatment of neurogenic detrusor overactivity (NDO) in a randomized, prospective, controlled, open-label, multi-center trial in 35 adult patients.NDO was confirmed within the previous 24 months by urodynamic studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin hydrochloride orally three times per day for a period of 28 days. Primary efficacy criterion was the change in the maximum bladder capacity between the beginning of the study and after 4 weeks as assessed by UDS. Adverse drug reactions (ADR) were collected and an evaluation of anticholinergic effects was conducted.The increase in maximum bladder capacity was 117 ml with intravesical application (P = 0.0002) versus 18 ml with the oral application (P = 0.51). The difference was statistically significant (P = 0.0086). ADR were reported by 10 (55.6%) of patients with intravesical administration, and by 14 (82.4%) of patients with oral administration. Significant differences in favor of the intravesical application were observed in ADR affecting vision (1/10 vs. 9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14), and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were reported.This study demonstrates the efficacy and safety of intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect to the increase in maximum bladder capacity. Neurourol. Urodynam. 35:582-588, 2016. © 2015 Wiley Periodicals, Inc.

Background: Insect venom immunotherapy (VIT) is initiated by a dose increase protocol administered usually over 7 to 9 days. Shorter protocols have the advantage of reducing the patient's stay in the hospital. Very few data are currently available on the safety of shorter VIT dose increase protocols. Objective: The aim of this study was to investigate whether a reduction in the duration of the VIT dose increase protocol from 7 to 9 days to 2 days causes an increase in the incidence and severity of adverse reactions. Methods: Between 1992 and 1997 we administered VIT to 1055 patients allergic to bee or wasp venom. We shortened the 7- to 9-day rush protocol stepwise to 2 days by reducing the number of injections and increasing the initial dose and compared the incidence and severity of adverse reactions. The patients were retrospectively divided into 3 cohorts: 20 injections over 7 to 9 days (cohort 1, 317 patients), 10 to 14 injections over 3 to 6 days (cohort 2, 335 patients), and 9 injections over 2 days (cohort 3, 403 patients). Results: We observed no severe adverse reactions in any of the cohorts during VIT. Adverse reactions were treated in 7.1% of the patients by oral and in 2.9% by intravenous antihistamines and in 0.8% by systemic corticosteroids. The incidence of adverse reactions declined significantly from 22.4% in cohort 1 to 13.7% in cohort 2 and 10.7% in cohort 3 with reduced number of injections ( P Conclusion: The incidence and severity of adverse reactions decline if the VIT dose increase protocol is shortened to 2 days. (J Allergy Clin Immunol 2000;105:1231-5.)

Objective: The SQ-standardised grass sublingual immunotherapy (SLIT) tablet, GRAZAX® (ALK, Denmark) has been shown to be efficacious and well tolerated in a large number of clinical trials performed in Europe and USA. The aim of this study was to investigate the administration of the SQ grass SLIT-tablet in a real life setting. Methods: This study was non-interventional, open-label, observational including 1,109 patients from 434 clinics in Germany treated between November 2006 and February 2009 with the SQ grass SLIT-tablet. Patients were followed at visits every 3 months for 9-12 months after start of therapy. Assessments included tolerability, compliance, patient satisfaction and treatment effect. Adverse drug reactions (ADRs) reported were coded by using the Medical Dictionary for Regulatory Activities (MedDRA). Results: A total of 534 (48.2%) patients experienced ADRs that were considered to be related to treatment in 299 (27.0%) patients. Treatment was discontinued in 98 (8.8%) patients due to ADRs. ADRs were experienced by 460 (41.5%) patients after first administration and classified in 440 (39.7%) patients as mild tolerable reactions at the application site needing no further treatment and in 20 (1.8%) patients as intolerable reactions and reactions that needed treatment by medication all of which are specified in the summary of product characteristics for GRAZAX®. Most frequently reported ADRs were paraesthesia oral, oedema mouth, oral pruritus, oral discomfort, swollen tongue and throat irritation. Serious ADRs related to treatment were reported by three patients, all patients fully recovered. Compliance (70.9%) and patient satisfaction with the treatment effect (92.6%) were high. Subjective well-being was improved in 74.7% of patients and symptoms and medication use were reduced versus previous seasons without SQ grass SLIT-tablet. Conclusions: Our results confirm that the SQ grass SLIT-tablet is well tolerated during routine administration. Compliance, patient satisfaction, and treatment effect were found to be high.

We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results.We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10 mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach.Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects.Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.

Background Oral allergy syndrome (OAS) triggered by fruit and vegetables often occurs in patients with pollen-induced rhinoconjunctivitis because of cross-reactive epitopes in pollen and associated foods. This open observational study examined the effect of pollen-specific sublingual immunotherapy ([SLIT] B. U. Pangramin or SLITone involving birch/alder/hazel, grasses/rye, and/or mugwort) on OAS triggered by several foods in patients treated in standard practice. Very few studies have examined SLIT use in this situation. Methods Patients (n = 102) had pollen-induced rhinoconjunctivitis and OAS and were followed for up to 12 months. Baseline OAS (triggers, symptoms, and symptom severity) was assessed by questionnaire and patient history. Change in OAS was assessed using oral challenge test with 1 or 2 dominant food triggers (and compared with the sum score calculated from the OAS questionnaire at baseline) and clinician ratings of change. Pollen-induced rhinoconjunctivitis symptoms and medication use were also measured. Results In the oral challenge test, 77.0% of patients were considered responders (decrease in sum score of ≥ 50%; no difference in patients receiving B. U. Pangramin or SLITone). At baseline, investigators rated OAS severity as at least moderate in 94.9% of patients compared with 36.9% after 12 months of treatment. After 12 months, OAS was rated as much or very much improved in 72.9% of patients. Sublingual immunotherapy significantly reduced rhinoconjunctivitis symptoms and medication use. Only 10% of patients experienced adverse drug reactions. Conclusion This study supplements the sparse literature on this topic and suggests that pollen-specific SLIT can reduce OAS triggered by pollen-associated foods in patients with pollen-induced rhinoconjunctivitis.

Background: For patients with pollen induced allergic rhinoconjunctivitis, a pre-seasonal start of subcutaneous specific immunotherapy is generally recommended in international guidelines. In a placebo-controlled trial intraseasonal up-dosing of subcutaneous immunotherapy to 10,000 SQ-U (Alutard SQ®) was shown to be well tolerated and to induce significant immunologic effects. The aim of our study was to investigate the feasibility of intra-seasonal up-dosing during routine application. Methods: In an open, non-interventional observational study, data on tolerability of subcutaneous immunotherapy (Alutard SQ®) in patients with grass pollen induced allergic rhinoconjunctivitis were recorded by 110 physicians between May and November 2009 in Germany. Therapy was initiated within grass pollen season according to a 6-injection up-dosing schedule from 100 to 10,000 SQ-U with 1-3 days intervals, repeating this dose after 2 and 4 weeks during and up-dosing to the final maintenance dose of 100,000 SQ-U after the end of grass pollen season. Results: Data for 250 patients could be evaluated, 198 patients had been up-dosed up to the peak grass pollen season and 52 after the peak. Adverse drug reactions were observed in 61.6% of patients with up-dosing up to the peak grass pollen season and in 48.1% with up-dosing after the peak with swelling at the injection site as most common reaction. The overall rate of systemic allergic reactions was low in both groups. Mild to moderate respiratory symptoms were more frequently reported in patients up-dosed up to the peak grass pollen season. Overall tolerability was assessed as “very good” or “good” by >90% of patients and physicians. Conclusions: Intra-seasonal short-time up-dosing with Alutard SQ® grasses and rye by 6 injections from 100 to 10,000 SQ-U with 1-3 days interval was observed to be well-tolerated during routine application and thus confirms data obtained from the placebo-controlled clinical trial.

Background: Efficacy and safety of the SQ-standardised grass allergy immunotherapy tablet (GRAZAX®) has been reported in a large number of randomised, controlled clinical trials in children and adults performed in Europe and the US. GRAZAX® became available for routine treatment in children from 5 years of age in Germany and Austria in 2008.To examine the safety and tolerability of GRAZAX® in patients that were less highly selected as in the controlled trials we performed an open label, uncontrolled, non-interventional study in children and adults who were routinely treated in allergists´ offices. Materials and methods: Patients with allergic rhinoconjunctivitis with or without asthma were treated with GRAZAX® and observed for 3-4 visits every 3 months with the last visit after the first grass pollen season. Adverse seasons before and during therapy. Results: Treatment was documented in 1,761 patients (797 75% in 89.8% of patients, >95% of patients and physicians were satisfied with treatment. Conclusion: The results of our study confirm the safety and tolerability profile observed in controlled clinical trials with GRAZAX®. Treatment satisfaction during routine application was rated high and was combined with a high compliance.

International guidelines recommend that allergen-specific immunotherapy for pollen-induced rhinoconjunctivitis is initiated preseasonally. However, because subjects often present to physicians with allergy symptoms during the pollen season, "within-season" initiation of specific immunotherapy is of special interest.We evaluated the immunomodulatory effects and tolerability of subcutaneous immunotherapy (SCIT) with Standardized Quality (SQ) 6-grass mix and rye allergen extract, using an 8-day intra-seasonal up-dosing schedule to 10,000 SQ-units (SQ-U).In a 9-week, multicenter, randomized, double-blind, placebo-controlled trial, adults (mean age, 34.6 years; 99.3% whites) with grass pollen-induced rhinoconjunctivitis (mean disease duration, 15.1 years) were randomized 3:1 to receive SCIT or placebo. Treatment was initiated during the 2008 pollen season, with an 8-day up-dosing from 100 to 10,000 SQ-U (6 daily injections) followed by 2 maintenance injections of 10,000 SQ-U at intervals of 2 and 4 weeks, respectively. The primary end point examined immunologic effects, assessing the difference in IgE-blocking factor (serum components competing with IgE for allergen binding) between SCIT and placebo at week 9. Secondary/explorative end points included the difference in IgE-blocking factor, specific IgG(4), and specific IgE at various times. Tolerability (adverse events, local and systemic allergic reactions) of the up-dosing schedule was also evaluated.Of the 148 treated subjects 144 (SCIT n = 109; placebo n = 35) were analyzed for the primary parameter. Immunologic response (significantly higher increase in IgE-blocking factor and IgG(4) levels) occurred with SCIT versus placebo at week 9 (IgE-blocking factor, P = 0.0017; IgG(4,)P = 0.0215). Significant differences were observed as early as week 3. AEs were reported in 60.7% of SCIT- and 30.6% of placebo-treated subjects, with no treatment-related serious AEs. Local allergic reactions occurred in 46.4% of SCIT and 8.3% of placebo subjects (χ(2) test, P0.0001). No significant difference was observed between groups in the incidence of systemic reactions (7.1% SCIT vs 5.6% placebo; χ(2) test, P = 0.7413).This trial provides the first description of short (8-day) intra-seasonal up-dosing with SCIT, which induced immunologic effects after only 3 weeks, and was generally well tolerated, although it induced a marked increase in the rate of local reactions compared with placebo. ClinicalTrials.gov identifier NCT00807547; ALK trial ID SHX0562.

Background: The outcome of meta-analyses and the interpretation of results might be influenced by the choice of studies included. For Memantine, it will be proved if additional trials influence the outcome of meta-analyses published so far.Methods:Meta-analysis were performed based on 7 and 9 randomised, double-blind, placebo controlled trials, respectively, to evaluate the impact of two trials (MD-22, published as study synopsis, http:// www.forestclinicaltrials.com; IE-2101, Homma et al. 2007, 11th EFNS Congress, Brussels) on the outcome of the meta-analysis. For analyses cma2’ was used, and results are multiplied by -1 to present the results with same polarity. Results: When comparing the results of the metaanalyses, there are only minor differences (see table) in the outcome for the domains relevant for Alzheimer’s disease.Conclusions:Both additional trials (IE-2101, MD-22) can be included in meta-analyses based on the results published so far. No relevant changes in effect sizes were observed when comparing meta-analyses with 9 and those with 7 trials. Robust and consistent results prove the benefit of Memantine for patients with moderate to severe AD.

Background: Development of cosmetic products and household detergents necessitates comparative study designs to assess the skin tolerance of products. In initial tests, the epicutaneous patch test for irritation is widely used. Objectives: This study was conducted to develop a protocol that would facilitate a comparison of results obtained when tests are conducted by different laboratories. Methods:‘In-house’ and standardized patch test protocols were used to assess irritation potentials of surfactant-based products in intra- and interlaboratory studies using defined surfactant samples. Results: The various in-house protocols tested did not consistently produce equivalent results. In order to develop a study design that yields comparable results, various factors were identified and adjusted. The standardized study protocol includes occlusive application of 70 µl of the test substance to the back of 30 subjects, defined reading times and schemes, assessments based mainly on erythema, and inclusion of sodium laureth sulfate and sodium dodecyl sulfate as positive controls as well as water as a negative control. Conclusions: Use of the standardized protocol and training of assessors improved the reliability and consistency of results whereby the irritation potentials of the references and test samples were ranked similarly by the laboratories.

Background National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. Objectives To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. Design, setting, and participants We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. Intervention Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. Measurements The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post–prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. Results and limitations In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract ( n =70) or placebo ( n =69). The individual domains pain ( p =0.0086) and quality of life (QoL; p =0.0250) as well as the total NIH-CPSI score ( p =0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% ( p =0.0141), respectively. Adverse events were minor in all patients studied. Conclusions Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.

Efficacy, cycle control, tolerance, and adverse events were studied in a clinical Phase IV study using a new progestogen, gestodene, in an amount of 75 micrograms combined with 30 micrograms ethinylestradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. Half of the patients taking the new preparation were first-time OC users, the other half switched from another OC. With regard to contraceptive efficacy, the life-table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl-Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in the trial. Dysmenorrhea present in the "switchers" mostly disappeared on the new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behaviour is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favourable effect on dysmenorrhea. The number of clinically diagnosed thrombotic events documented in this study was 0.65 per 1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using non-hormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).Efficacy, cycle control, tolerance, and adverse events were studied in a clinical phase IV study using a new progestogen, gestodene, in an amount of 75 mcg combined with 30 mcg ethinyl estradiol. The study was performed as a multicenter trial in 96,000 patients over a period of 6 cycles. 1/2 of the patients taking the new preparation were 1st-time OC users, the other 1.2 switched from another OC. With regard to contraceptive efficacy, the life table analysis showed a value of 0.032% for method failure and 0.114% for patient failure. The correspondent Pearl Index is 0.062 and 0.22. The new drug was found acceptable by more than 90% of the women involved in this trial. Dysmenorrhea present in those who switched disappeared for the most part with this new OC, while body weight and blood pressure remained virtually unchanged. Thus, it can be concluded that blood pressure and body weight behavior is similar to that seen with other low-dose OCs. The new combined pill offers excellent cycle stability and has a very favorable effect on dysmenorrhea. The number of clinically diagnoses thrombotic events documented in this study was 0.65/1000 woman-years (TWY) and does not exceed the range of events seen in groups of women using nonhormonal methods of contraception (Oxford-FPA study 0.4/TWY and RCGP study 0.8/TWY).

The aim of this study was to investigate the effect of potassium paraaminobenzoate (Potaba) in Peyronie's disease in a prospective, randomized, double-blind, placebo-controlled, multicentre study during a 12-months period of treatment.103 patients with Peyronie's disease and a history12 months, non-calcified plaques and without pre-treatment were included. 51 were randomized to potassium paraaminobenzoate, 52 to placebo receiving 4 x 3g/day for 12 months. Follow-up was performed during the treatment period. Response has been defined as regression in plaque-size and/or reduction in penile curvature of at least 30%. Data analysis was focussed on 75 patients who completed the study [valid-cases (VC)].No severe adverse events occurred. Response rates were 74.3% on potassium paraaminobenzoate and 50.0% on placebo (p=0.016). Mean plaque-size decreased from 259 mm(2) to 142 mm(2) in the treatment arm. In the placebo group, plaque-size aggravated from 259 mm(2) to 303 mm(2) after 6 months but improved slightly to 233 mm(2) after 12 months. Differences between the groups were significant (p=0.042). Pre-existing curvature did not improve under the drug (p=0.066) but comparing the development of new curvature or deterioration of pre-existing curvature under potassium paraaminobenzoate penile deviation remained stable. However, under placebo penile curvature deteriorated significantly in 32.5% of the cases (p0.001). No significant differences concerning decrease of pain could be observed between the two groups (82.6% vs. 77.3%).The results of this study indicate a significant plaque-related effect of potassium paraaminobenzoate. There was no relevant difference with regard to improvement of pre-existing penile deviation. However, under potassium paraaminobenzoate a significant protective effect on deterioration of penile curvature could be demonstrated. Potassium paraaminobenzoate appears to be useful to stabilize the disorder and prevent progression of penile curvature.

Chronic levodopa (L-dopa) treatment of Parkinson’s disease (PD) patients is sooner or later associated with the onset of motor complications, for example wearing off and dyskinesia. PD patients with motor complications usually require the addition of further PD drugs to reduce these L-dopa side effects and enhance its efficacy. Entacapone is an available catechol-O-methyltransferase (COMT) inhibitor, which was extensively investigated as add-on to L-dopa/dopadecarboxylase inhibitor (DDCI) application in PD patients. Safinamide, a watersoluble, orally active a-aminoamide derivative, which modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action, has been studied in two placebo-controlled clinical trials as add-on therapy to L-dopa in fluctuating PD patients. To date, there are no head-to-head clinical trials comparing the efficacy of safinamide and entacapone in the clinic. The aim of this meta-analysis was to determine effect sizes of safinamide and entacapone as add-on treatment to L-dopa in fluctuating PD patients. A systematic search of the literature on entacapone trials up to the end of September 2014 was first conducted on the MEDLINE and EMBASE databases in order to identify appropriate studies. Definition criteria for inclusion were prospective, randomised, placebocontrolled and double-blinded trials on the efficacy and safety of entacapone or safinamide in fluctuating L-dopa-treated PD patients. Four studies for entacapone and two trials on safinamide were considered. Data from the safinamide trials were provided by Zambon and therefore ‘safinamide’ was not used as a search term. Safinamide and entacapone treatment was comparable in terms of the main efficacy variables (offtime, percentageontime, Unified Parkinson’s Disease Rating Scale). Significant advantages in favour of safinamide were shown in terms of the total incidence of adverse events (AEs) in comparison to placebo, the study discontinuation due to AEs and deaths and in the risk differences of the AEs versus placebo, particularly for nausea, vomiting, diarrhoea, dizziness, urine abnormality and shortness of breath. The odds ratio (OR) of 0.907 for any AE corresponds to an overall AE rate of 68.7 % for safinamide whereas the OR of 2.089 to an overall AE rate of 84.4 % for entacapone.

Activation of mast cells and eosinophils under pollen exposure can be inhibited by specific immunotherapy.The effect of short-term immunotherapy with 7 preseasonal injections of molecular standardized allergens from grass and rye pollen on eosinophil cationic protein (ECP) and tryptase levels in nasal secretions has been compared with symptomatic drug treatment in an open, randomized study with 48 patients.Nasal reactivity and mediator levels in nasal secretions were measured at baseline, before season, in season, and after season.Symptom scores in the immunotherapy group were 134.5 (95% CI, 65 to 336) versus 386. 0 (95% CI, 185 to 563), significantly lower as in the drug-treated group. ECP and tryptase levels increased significantly during natural allergen exposition. The seasonal levels in the immunotherapy group were significantly lower than in the drug-treated group with 272.1 ng/mL (252.0 to 293.9 ng/mL; immunotherapy) versus 470.4 ng/mL (SEM, 435.6 to 508.0 ng/mL; drugs) for ECP and with 8.73 ng/mL (SEM, 8.20 to 9.29 ng/mL) versus 17.47 ng/mL (16.42 to 18.60 ng/mL) for tryptase (all, P.001). The ECP level induced by nasal provocation was 105.6 ng/mL (99.0 to 112.6 ng/mL) versus 180.4 ng/mL (169.2 to 192.4 ng/mL), significantly lower (P.001) in the immunotherapy group, as was the tryptase level with 12.12 ng/mL (11.53 to 12.75 ng/mL) versus 8.19 ng/mL (7. 79 to 8.62 ng/mL; P.001) at the after-season visit.Short-term immunotherapy is able to reduce tryptase and ECP in nasal secretions more effectively than drug treatment in patients with allergic rhinitis.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Fruhbluhermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P

Background By now, the efficacy and safety of sublingual immunotherapy (SLIT) have been well established, but as for all long-term treatments, adherence to the treatment is essential. Patient-related outcome measures, such as the patients' satisfaction with the treatment, have become more crucial for they may affect treatment adherence. Methods To evaluate patient satisfaction with SLIT treatment (Staloral, Stallergenes S.A., France) we designed a prospective, observational, multicenter study. Treatment satisfaction was measured using the QUARTIS questionnaire (= Questionnaire on Respiratory Allergies Treated by Sublingual Immunotherapy). As medical parameters effectiveness and adverse events were documented. Patients with allergic rhinitis and/or conjunctivitis due to tree pollen, grass pollen or house dust mites were included in the study. Results 226 patients (94 male, 132 female, median age 37 years) participated in this study. Treatment satisfaction: Compared to a period before treatment, patients reported improved nasal symptoms (13.03 vs. 9.70; P < 0.0001) and eye symptoms (6.11 versus 4.43; P < 0.0001). After treatment, the allergy was less bothersome in everyday life (9.62 versus. 7.27; P < 0.0001). 69.2% of treated patients experienced a better tolerability than they had expected. No relevant differences were observed between the different allergen groups. Effectiveness: The severity of nasal symptoms was reduced by 53.2% (2.35 versus 1.10; P < 0.0001). For eye symptoms the severity was reduced by 57.0% (2.14 versus 0.92; P < 0.0001). Only 36.1% of the patients needed symptomatic medication in the treatment period compared to 70.1% before treatment. 88.0% of the investigators assessed the patients' well-being as "much better" or "better" after treatment. Adverse events: The overall tolerability was assessed as "good" or "very good" in approximately 90% of the evaluable cases. Only 11.9% of patients experienced adverse events (AEs). The most common AEs were gastrointestinal disorders. Conclusions Patients treated with SLIT in a real-life setting were satisfied with the treatment: It was tolerated well, patients' symptoms improved and their allergy had less impact on daily life. The patients' high level of treatment satisfaction as well as the good tolerability and effectiveness of the extract are important factors for they may help to improve treatment adherence.

The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. No methodologically detailed work on the utility of the scale to assess health-related changes after treatment was published before. We analysed an open, uncontrolled post-marketing study with over 9000 women with pre- and post-treatment data of the MRS scale to critically evaluate the capacity of the scale to measure the health-related effects of hormone treatment independent from the severity of complaints at baseline. The improvement of complaints during treatment relative to the baseline score was 36% in average. Patients with little/no complaints before therapy improved by 11%, those with mild complaints at entry by 32%, with moderate by 44%, and with severe symptoms by 55% – compared with the baseline score. We showed that the distribution of complaints in women before therapy returned to norm values after 6 months of hormone treatment. We also provided weak evidence that the MRS results may well predict the assessment of the treating physician. Limitations of the study, however, may have lead to overestimating the utility of the MRS scale as outcome measure. The MRS scale showed some evidence for its ability to measure treatment effects on quality of life across the full range of severity of complaints in aging women. This however needs confirmation in other and better-designed clinical/outcome studies.

Background and Objective Allergy immunotherapy (AIT) with the SQ® grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious, well-tolerated and to improve disease-specific health-related quality of life (HRQoL) in controlled clinical trials. The aim of our study was to investigate HRQoL in patients with allergic rhinoconjunctivitis routinely treated with the SLIT-tablet and taking symptomatic medication as needed compared with patients treated only with symptomatic medication. Methods In a non-interventional, open-label study, patients treated with the SLIT-tablet were observed for about 12 months compared with patients only symptomatically treated. Patients assessed their HRQoL with the 12-Item Short Form Health Survey (SF-12) and the Rhinitis Quality of Life Questionnaire (RQLQ) in the grass pollen seasons (GPS) at baseline (GPS1, HRQoL1), after GPS1 (HRQoL2) and in the following GPS (GPS2, HRQoL3). Tolerability, compliance, symptoms and medication use were assessed in the SLIT-tablet group by the physician. Results Overall, data were analysed in 576 patients. Mean differences (±SD) in overall scores for HRQoL3 versus HRQoL1 (186 patients) of SF-12 were +11.4 ± 16.8 (SLIT-tablet) and −3.4 ± 15.7 (symptomatic medication), (p

Background and Objective For specific immunotherapy to pollen allergy, a pre-seasonal start of treatment is recommended by international guidelines. In a placebo-controlled clinical trial with adults, an intra-seasonal start of therapy with the SQ-standardised grass allergy immunotherapy tablet (AIT) was well-tolerated. The objective of our study was to investigate the feasibility of an intra-seasonal start of grass AIT administered during routine treatment by practising allergists. Methods In a multicentre, prospective, open-label, uncontrolled, non-interventional observational study, data on routine treatment with grass AIT were recorded in patients who started administration of tablets within the 2010 grass pollen season in Germany. Adverse events (AEs) were recorded by the physician at visits for the first administration in the clinic and at the end of the 1- to 3-month observation period. AEs and daily administration of the tablet were recorded by the patients in diaries for the first 14 days. Treatment satisfaction, global tolerability and perceived effect of treatment were assessed by the patient and physician at the end of the study. Results A total of 662 patients were treated with 1 tablet daily by 286 physicians. Grass AIT was started intra-seasonally in 620 patients and post-season in 42. The average treatment period was 51.6 days. AEs were recorded in 52.1 % of all patients and in 35.6 % at first administration, with throat irritation (21.3 %), paraesthesia oral (19.9 %), oral pruritus (14.0 %) and ear pruritus (10.3 %) being the most frequent AEs related to grass AIT. The intensity of the AEs was assessed as mild or moderate in 42.1 % of patients and severe in 8.0 %; AEs related to grass AIT were classified as serious in two patients. Grass AIT was discontinued due to AEs in 7.7 % of patients. Diaries were evaluable for 77.0 % of patients; the average rate of patients with AEs decreased continuously from 44.7 % (day 1) to 26.9 % (day 14) and the average daily rate of patients who forgot to take their tablet was about 5 %. Overall tolerability was assessed by 87.2 % of patients and 91.4 % physicians as “very good” or “good” and effectiveness of treatment was assessed as “very good” or “good” in 81.4 % of patients and 85.8 % of physicians. More than 90 % of patients and physicians were satisfied with the treatment. Conclusion The tolerability data for an intra-seasonal start of grass AIT during routine treatment confirm the safety profile from the previous controlled trial. Tolerability was assessed as good in combination with high satisfaction with the treatment and compliance.

Therapy with the SQ®-standardised grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious and well-tolerated in a large clinical development programme. The objective of this study was to investigate patients’ satisfaction with treatment by the SQ® grass SLIT-tablet during routine application. In the setting of a non-interventional, open-label, observational study, patients with allergic rhinoconjunctivitis were started on the SQ® grass SLIT-tablet 4–5 months before the grass pollen season and were followed until the end of the season. Treatment satisfaction was assessed by patients completing the Treatment Satisfaction Questionnaire for Medication (TSQM II, German version 1.4) before and after the grass pollen season. Compliance and changes in subjective well-being were also assessed. Data of 271 patients treated with the SQ® grass SLIT-tablet by 117 allergists in Germany were analysed. The TSQM score for global satisfaction was (mean ± standard deviation) 79.40 ± 19.98 after 6–9 months of therapy, with the highest scores for the dimensions side effects (92.89 ± 16.49) and convenience (88.19 ± 14.33), followed by effectiveness (70.74 ± 25.20). Treatment effect was assessed by the treating physician as very good or good in 83.1% of patients. The subjective well-being of the patients compared with the previous years was assessed as improved by 87.8% of the patients at the end of the study. Global satisfaction measured with the TSQM in patients treated with the SQ® grass SLIT-tablet was high, with the highest scores in the dimensions side effects and convenience, followed by effectiveness, and increased between 3 months and 6–9 months of treatment initiation. ALK-Abello Arzneimittel GmbH

Background The majority of allergic patients are poly-sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ® grass SLIT-tablet and were treated with concomitant AIT products. Methods In a non-interventional, open-label, observational study in Germany treatment of patients with the SQ® grass SLIT-tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ® grass SLIT-tablet and after 1–3 months of treatment. Tolerability of the treatment with the SQ® grass SLIT-tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities. Results In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3 %) patients with concomitant AIT, and AEs considered related with the SQ® grass SLIT-tablet in 49 (30.6 %) and with concomitant AIT in 18 (11.3 %) patients. Treatment was discontinued due to ADRs in 12 (7.5 %) patients and severity of ADRs was assessed mild or moderate in 29 (18.1 %), and severe in 20 (12.5 %) patients. Most common reactions were localised at the application site of the SQ® grass SLIT-tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ® grass SLIT-tablet if given with concomitant AIT was assessed as “good” or “very good” by 91.0 % of patients and 91.6 % of physicians. Conclusions In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ® grass SLIT-tablet was administered with concomitant SCIT or SLIT.