Safety and efficacy of venom immunotherapy: a real life study.

INTRODUCTION: Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. AIM: To analyze the safety and efficacy of VIT in a real life setting. MATERIAL AND METHODS: One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. RESULTS: Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p < 0.0001). Early and late side effects were more common during the maintenance (48 patients, 26.7%) than during the induction of VIT (32 patients, 17.8%), were more frequent in patients allergic to bees, and were not associated with angiotensin convertase inhibitors (ACEi) or ß-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received (r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p < 0.0001) and female sex (RR = 1.27, p = 0.033) were associated with a higher risk of venom allergy. CONCLUSIONS: Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

Classification model of amino acid sequences prone to aggregation of therapeutic proteins.

BACKGROUND: Total body clearance of biological drugs is for the most part dependent on the receptor mechanisms (receptor mediated clearance) and the concentration of antibodies aimed at administered drug - anti-drug-antibodies (ADA). One of the significant factors that induces the increase of ADA level after drug administration could be the aggregates present in the finished product or formed in the organism. Numerous attempts have been made to identify the sequence fragments that could be responsible for forming the aggregates - aggregate prone regions (APR). PURPOSE: The aim of this study was to find physiochemical parameters specific to APR that would differentiate APR from other sequences present in therapeutic proteins. METHODS: Two groups of amino acid sequences were used in the study. The first one was represented by the sequences separated from the therapeutic proteins (n = 84) able to form APR. A control set (CS) consisted of peptides that were chosen based on 22 tregitope sequences. RESULTS: Classification model and four classes (A, B, C, D) of sequences were finally presented. For model validation Cooper statistics was presented. CONCLUSIONS: The study proposes a classification model of APR. This consists in a distinction of APR from sequences that do not form aggregates based on the differences in the value of physicochemical parameters. Significant share of electrostatic parameters in relation to classification model was indicated.

Comparison of bioequivalence study regulatory requirements for human and veterinary drugs.

Guidelines published by the European Union Regulatory Authority, regarding the planning of bioequivalence studies, are the primary source of knowledge about the study design optimization. The goal of this paper is to compare the key elements (27 points) of bioequivalence study optimization based on a comparison of the two European Medicines Agency guidelines relating to medicines used for humans (HB) and to veterinary drugs (AB). In case of the latter, one can get the impression that the issues of species differences in relation to the physiology and anatomy have been completely ignored. Many details that the AB guideline omits are included in the new HB guideline and were present in many other guidelines from the last 20 years. Most have not been adopted by the AB document, even though they are the product of many years of work of many teams and specialists from various agencies in the regulatory affairs field.

Harmonization of rules in GLP and pharmacokinetic analysis: regulatory view.

This article is an attempt to present issues associated with the principles of GLP system harmonization, particularly in relation to pharmacokinetic (PK) studies at a global scale. Complete harmonization of GLP principles requires unification at several levels: inside registration authorities, between key registration authorities, within the framework of procedures regulating preclinical and clinical phases of the drug-development process and within the framework of procedures regarding GLP principles used in PK analyses and analyses of residuals of veterinary drugs. This large number of discrepancies indicates that total harmonization of rules on this issue will be very difficult and will require close cooperation between institutions responsible for legislative processes and control of GLP principles during PK analysis.