SCIT with a high-dose house dust mite allergoid is well tolerated: safety data from pooled clinical trials and more than 10 years of daily practice analyzed in different subgroups.

BACKGROUND: Efficacy of house dust mite (HDM) allergen immunotherapy (AIT) in allergic rhinitis and controlled allergic asthma has been documented in controlled trials with adults and children. However, tolerability comparing clinical development and post marketing data, particularly in different subgroups, is missing. METHODS: We performed an analysis of pooled safety data for subcutaneous AIT (SCIT) with a high-dose house dust mite allergoid from 6 randomized, controlled trials (RCT) in HDM allergic respiratory disease (ARD) and of post marketing safety data from more than 10 years including different subgroups (age, gender, asthma status). RESULTS: In all, 500 patients with ARD were treated in RCTs: 279 received the marketed dose of 1800 protein nitrogen units (PNU) high-dose HDM allergoid AIT (214 double-blind placebo controlled [HDM-DBPC], 65 children/adolescents usual care controlled [HDM-RCT(UC)]), and 221 placebo (PL). 38.8% adverse events (AEs) were observed with 1800 PNU in HDM-DBPC (31.2% PL, 35.5% HDM-ALL [1800 PNU]); the difference was primarily because of local reactions; there was no difference in systemic reactions (10.9% PL, 11.2% HDM-DBPC, 11.2% HDM-ALL); one out of 279 high-dose HDM allergoid-treated patients had a serious adverse event (SAE).Children (n = 39)/adolescents (n = 26) had fewer related AEs and local reactions compared to adults; systemic reactions: children 12.8%, adults 11.2% adolescents 7.7%. Females had slightly more AEs. Treatment was well tolerated in asthmatic patients (n = 267; GINA I n = 32, II n = 104, III n = 17, 114 no classification).In more than 10 years more than 100,000 patients were treated with high-dose HDM allergoid (1800 PNU) under daily practice conditions. Adverse drug reactions (ADRs) were reported in 0.5% of patients. 94.6% of these ADRs were expected. CONCLUSION: SCIT with the marketed dose of high-dose HDM allergoid was well tolerated in clinical development and in daily practice. There was no increased risk for the investigated patient subgroups. Tolerability was comparable to HDM sublingual immunotherapy (SLIT) tablets.

Effects of Oxygen Supply During Training on Subjects With COPD Who Are Normoxemic at Rest and During Exercise: A Blinded Randomized Controlled Trial.

BACKGROUND: It is well established that physical training enhances functionality and quality of life in patients with COPD. However, little data exist concerning the effects of the usefulness of oxygen supply during exercise training for > 3 months in patients with COPD who are normoxemic at rest and during exercise. We hypothesized that oxygen supply during training sessions enables higher training intensity and thus optimizes training results in patients with COPD. METHODS: In this blinded randomized controlled study, we carried out a 24-week training program with progressively increasing loads involving large muscle groups. In addition, we compared the influences of oxygen supplementation. Thirty-six subjects with moderate-to-severe COPD who were not dependent on long-term oxygen therapy trained under supervision for 24 weeks (3 times/week at 30 min/session). Subjects were randomized into 2 groups: oxygen supply via nasal cannula at a flow of 4 L/min and compressed air at the same flow throughout the training program. Lung function tests at rest (inspiratory vital capacity, FEV1, Tiffeneau index), cycle spiroergometry (peak ventilation, peak oxygen uptake, peak respiratory exchange rate, submaximal and peak lactic acid concentrations), 6-min walk tests, and quality-of-life assessments (Medical Outcomes Study 36-Item Short Form questionnaire) were conducted before and after 12 and 24 weeks. RESULTS: Independent of oxygen supplementation, statistically significant improvements occurred in quality of life, maximal tolerated load during cycling, peak oxygen uptake, and 6-min walk test after 12 weeks of training. Notably, there were no further improvements from 12 to 24 weeks despite progressively increased training loads. CONCLUSIONS: Endurance training 3 times/week resulted in significant improvements in quality of life and exercise capacity in subjects with moderate-to-severe COPD within the initial 12 weeks, followed by a stable period over the following 12 weeks with no further benefits of supplemental oxygen.

Efficacy and tolerability of Entacapone versus Cabergoline in parkinsonian patients suffering from wearing-off.

In this 12-wk, multi-center, randomized, open-label, rater-blinded study, efficacy and tolerability of Entacapone (ENT) or Cabergoline (CBG) in conjunction with levodopa were compared in 161 older Parkinson's disease patients with wearing-off. Patients received either ENT, 3 to 5 times daily, or CBG, titrated according to requirements to a maximum of 6 mg/d. A significant decrease of nearly 2 hours in the daily OFF-time (primary efficacy variable) was recorded in both treatment groups. The non-inferiority test failed despite a trend in favor of ENT. Reduction in OFF-time occurred faster in the ENT compared to the CBG treated patients. A decrease of approximately 20% was detected in parts II and III of the UPDRS, with no differences between the groups. Forty-three percent of the patients in the ENT group reported dyskinesias at baseline, and 35% at the final visit. The corresponding figures in the CBG group were 46% and 43%. Quality of life, measured by PDQ-39, increased substantially with both ENT and CBG. The mean daily dosage at the final visit was 698 mg for ENT (plus 447 mg levodopa) and 3.45 mg for CBG (plus 475 mg levodopa). Adverse events (AE), leading to discontinuation, were reported in 8.5% of the ENT and 13.9% of the CBG treated patients. Nausea was the most common AE in each group, corresponding figures being 7.3% with ENT and 25.3% with CBG (P=0.0024). A probable or possible causal relationship with ENT was reported in 41% and with CBG in 64% of the AE. Among these, only one serious AE (dehydration) was recorded with each treatment group. ENT and CBG reduced the patient's motor complications effectively and to a similar degree. The clinical benefit was more quickly apparent with ENT, which also showed a more favorable AE profile than CBG.