Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

AIM: To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. METHODS: In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. RESULTS: Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. CONCLUSION: This study found 1000 UA/day to be the optimal effective and safe dose.

Conjunctival provocation tests: a predictive factor for patients' seasonal allergic rhinoconjunctivitis symptoms.

BACKGROUND: No parameters currently exist that can reliably predict the impact of preseasonal immunotherapy on the symptoms occurring during the season. OBJECTIVE: The purpose of our studies was to prove a correlation between preseasonal conjunctival allergen challenge and coseasonal primary clinical endpoints using the total combined score, ie, a combination of symptoms and medication score, as the primary outcome parameter. METHODS: Twelve weeks before both the birch and the grass pollen seasons, 2 separate prospective, double-blind, randomized, controlled studies were conducted followed by posttrial observations for each study during the active season. In the studies, patients who reacted to conjunctival allergen challenge were treated with sublingual immunotherapy tablets that contain either birch and/or alder or grass pollen allergoids. RESULTS: In all, 158 patients were included in the grass and 160 in the tree pollen study; of these, 100 and 109 patients, respectively, took part in the posttrial observations. When comparing patients with and without a positive reaction in the final conjunctival allergen challenge, the results revealed a significant difference in the total combined score (grass: P < .001; birch: P = .025). The same applied to the rescue medication score (P = .005; P = .025). A significant difference regarding the rhinoconjunctivitis symptom score was shown in the grass pollen study (P = .002), and the difference of well days was significant in the tree pollen study (P = .049). CONCLUSION: When comparing patients based on their reaction to allergen challenge after immunotherapy, each study leads to similarly significant results. Therefore, conjunctival allergen challenge can be used effectively as a parameter to predict allergic rhinoconjunctivitis symptoms during the season in patients treated with preseasonal sublingual immunotherapy tablets. Whether this can be transferred to untreated patients needs to be determined.

Meta-analysis of the efficacy of ectoine nasal spray in patients with allergic rhinoconjunctivitis.

Objectives. The meta-analysis aims to investigate the efficacy of ectoine nasal spray and eye drops in the treatment of allergic rhinitis and rhinoconjunctivitis symptoms. Design and Methods. This meta-analysis is based on yet unpublished data of four studies. Both nasal and eye symptoms were documented in patient diary cards. All scales were transformed into a 4-point scale: 0 = no, 1 = mild, 2 = moderate, and 3 = severe symptoms. Each symptom was analysed individually in a meta-analysis of the area under the curve values as well as in a meta-analysis of pre- and posttreatment comparison. Results. After seven days of treatment with ectoine nasal spray both nasal and ocular symptoms decreased significantly. A strong reduction of symptom severity was shown for the parameters rhinorrhoea (31.76% reduction) and nasal obstruction (29.94% reduction). Furthermore, the meta-analyses of individual symptoms to investigate the strength of effect after seven days of medication intake showed significant improvement for nasal obstruction, rhinorrhoea, nasal itching, sneezing, itching of eyes, and redness of eyes. The improvement of the symptom nasal obstruction was associated with a strong effect 0.53 (±0.26). Conclusions. The ectoine nasal spray and eye drops seem to be equally effective as guideline-recommended medication in the treatment of rhinoconjunctivitis symptoms.

A prospective, controlled study of SNS01 (ectoine nasal spray) compared to BNO-101 (phytotherapeutic dragées) in patients with acute rhinosinusitis.

OBJECTIVES: In this observational study, data on the efficacy, effects on quality of life and tolerability of the topical formulation SNS01 (Ectoin Rhinitis nasal spray) were compared to those of BNO-101 (Sinupret forte dragées) in patients with acute rhinosinusitis in the ear, nose, and throat (ENT) clinical setting. DESIGN AND METHODS: Patients with the diagnosis of acute rhinosinusitis were included in this non-interventional study with a treatment duration of 14-16 days. They received either a herbal phytotherapeutic dragée (control) or an ectoine-based nasal spray (investigational product), each to be taken according to the instructions for use (IFU) and summary of product characteristics (SPC). At each visit, the physician performed a nasal endoscopy, recorded the Sinusitis Symptom Score and checked for adverse events. During the entire treatment period, patients recorded the Sinusitis Symptom Score in patient diaries. In addition, patients receiving the nasal spray filled out a questionnaire to assess the tolerability of the treatment. To investigate effects on quality of life patients were asked to fill out the German version of a sinusitis-specific HRQL (health related quality of life) questionnaire. CLINICAL TRIAL REGISTRATION: NCT01684540. RESULTS: Patient diary entries, the assessment of the Sinusitis Symptom Score and the HRQL questionnaire demonstrated that the ectoine nasal spray was as effective as the phytotherapeutic dragées in treating acute rhinosinusitis. After two weeks of treatment, the assessments of both the patients' diaries and physicians' record forms indicated statistically significant improvement (p ≤ 0.001) in the symptom scores of the two groups (57.8% improvement for ectoine and 49.3% improvement for the phytotherapeutic dragées compared to baseline). Also, overall scores of 80 in the sensory questionnaire confirmed the good tolerability of the nasal spray. Correspondingly, HRQL improved significantly over the course of the treatment in both groups. CONCLUSION: SNS01 and BNO-101 demonstrated comparable effects in the treatment of acute rhinosinusitis. LIMITATIONS: Following German regulations, this trial was set up as an observational 'non-interventional' study, which does not allow for a placebo group or randomization of patients. Although the grade of evidence delivered by the study data is thus reduced from Ib to IIa, it does, however, reflect a realistic view of the most common clinical practice.

Comparability of subcutaneous and sublingual immunotherapy outcomes in allergic rhinitis clinical trials.

PURPOSE OF REVIEW: To conduct a qualitative comparison between the primary and secondary outcomes used in clinical trials of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis. RECENT FINDINGS: Studies of SCIT and SLIT for allergic rhinitis published up to January 2012 were included in this systematic review. Different ways of defining primary and secondary outcome parameters in studies investigating specific immunotherapy are described. Whereas older studies often use the total symptom score and the total medication score individually for the primary efficacy analysis, more recent studies follow current international recommendations of applying the total combined score as primary outcome measure. Even wider is the range of secondary outcomes in clinical trials with few being validated or standardized. SUMMARY: As already recognized as a major concern in recent literature, standardized and validated primary endpoints are of paramount importance in order to improve the comparability of study results. The lack of consistency in the selection of primary outcome parameters represents a major problem when comparing the same therapeutic intervention. A main point of concern is the absence of validation data for those primary and secondary outcomes selected. In conclusion, the qualitative analysis of well powered studies confirms an urgent call from academics, regulatory agencies and the pharmaceutical industry for validated primary outcome parameters and standardized definitions.