Grzegorz Cessak

TNF inhibitors – Mechanisms of action, approved and off-label indications

Tumor necrosis factor inhibitors (TNFi) belong to the group of biologic drugs, holding presently top positions on lists of most profitable products for pharmaceutical companies. Although current indications for TNFi include only selected diseases with an established role of immune dysfunction in their pathogenesis, studies on new indications are being carried out all over the world. The most important aspect of TNFi therapy is a targeted therapeutic approach, allowing to avoid a wide range of side effects associated with treatment with nonspecific immunosuppressive agents. Results of the trials on TNFi in the approved indications are widely accessible and analyzed elsewhere, both in primary publications as well as in systematic reviews and meta-analyses. Here we aim to discuss their mechanisms of action, and approved, as well as off-label indications of TNFi. In addition, we present comprehensive evidence on TNFi in treatment of rheumatoid arthritis (RA); the first authorized and probably most extensively developed indication for the majority of TNFi.

Targeting of calcitonin gene-related peptide action as a new strategy for migraine treatment

Migraine is a chronic, recurrent disorder, characterized by attacks of severe pain, affecting around 1% of adult population. Many studies suggest, that trigeminovascular system plays a key role in pathogenesis of migraine and other primary headaches. Calcitonin gene-related peptide (CGRP) is an endogenous substance, which is regarded a key mediator released from trigeminovascular system after stimulation of sensory nerve endings, responsible for dilatation of peripheral vessels and sensory transmission. CGRP is and extensively studied peptide as one of the most promising targets in migraine drug research. In the article we focus on the role of CGRP in the pathophysiology of migraine and present current data on CGRP antagonists and CGRP monoclonal antibodies.

Regulatory and clinical aspects of psychotropic medicinal products bioequivalence

Introduction of generic medicinal products to the market has increased access to modern therapies but also enabled significant reduction in their cost, leading to containment of public expenditures on medicinal products reimbursement. The critical assessment of bioequivalence of any reference medicinal product and its counterpart is based on comparison of their rate and extent of absorption. It is assumed that two medicinal products are bioequivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. Bioequivalent medicinal products are declared to be also therapeutically equivalent and can be used interchangeably. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of this article is to provide a description of rules that guide registration of generic medicinal products in the European Union and to analyze specific examples from the scientific literature concerning therapeutic equivalence of reference and generic antidepressant and antipsychotic medicinal products.

Bioequivalence and therapeutic equivalence of psychotropic drugs

Introduction to the market of generic drugs has increased access to modern therapies and enabled significant reduction of their cost, leading to containment of public expenditures on drug reimbursement. The assessment of bioequivalence of reference and generic drugs is based on the assumption that two different drug products are equivalent when their rate and extent of absorption do not show significant differences when administered at the same dose under similar experimental conditions. However, despite regulatory declaration, switching from reference to generic drugs is often associated with concerns of healthcare providers about decreased treatment effectiveness or occurrence of adverse drug reactions. The aim of the present research was to retrospectively study therapeutic equivalence of selected reference and generic psychotropic drugs. In our preliminary data we show, that no significant differences in clinical outcome was observed in patients after the switch. It indicates, that bioequivalent drugs are also therapeutically equivalent and can be used interchangeably.

Review/Praca poglądowaBioequivalence and therapeutic equivalence of psychotropic drugsRównoważność biologiczna i terapeutyczna leków psychotropowych

Objective It is the objective of this paper to discuss the requirements that must be met by generic drugs and explain basic concepts relating to bioequivalence. The authors have also included two tables listing the trading names of antidepressants and antipsychotics, with a valid authorization for marketing in Poland, which might prove helpful in daily psychiatric practice.

Assessment of Generic Psychotropic Drugs Therapy Costs in Poland

Provision of cost-effective drug treatment is of particular importance in patients with psychiatric diseases. Most of the therapies in question requires life-long treatment and consists of more than one medicine. Introduction of generic drugs is one of the major strategies for reducing contribution of costs of medications to total healthcare costs. The primary evidence required both by FDA and EMA for marketing approval of a new generic drug is acceptable bioequivalence between the generic drug product and its corresponding reference product. The price of the generic drug is estimated to be 25% lower comparing with the reference product. In the present study a comprehensive cost analysis of a two-year psychotropic drug treatment in one of high reference Polish psychiatric hospitals has been performed. The total real costs have been compared with predictable costs of treatment with reference products if used instead of the available generic drugs. Our study due to the comprehensive analysis of both the availability and costs of psychotropic medicinal products in Poland.

Systematic Review of Venous Thromboembolism Risk in Antipsychotics-exposed Patients

Many studies suggest an association between the use ofantipsychotic medicines (APs) and occurrence of venous thromboembolism (VTE). Thromboembolismis often associated with a significant risk of disability or death, and alsoplays a role in significantly increasing treatment costs. Despite many years of research on theassociation between the use of APs and VTE, specific pathogenetic mechanismshave not been identified. In the present study we searched available electronic medical databases(MEDLINE, PubMed, EMBASE) using a comprehensive search strategy. All steps wereperformed by at least 2 analysts in compliance with current Cochrane Handbook for Systematic Reviewsof Interventions. The primary outcome measure of this systematic review was theoccurrence of VTE (both DVT and/or PE) in patients exposed to AP drugs. Based on theidentified reports it has been determined that the main risk factors for VTE are duration oftreatment and patient-related factors, such as gender, age, body mass or physical activity. Currentdata does not allow identifying prothrombotic potential for individual APs. Allpatients treated with APs should be assessed with regard to the risk of thromboemboliccomplications and, if needed, appropriate prevention methods (most of all including eliminationof modifiable risk factors) should be implemented. Moreover, patients should be educatedabout symptoms suggesting VTE. Each patient with suspected VTE should be diagnosed andtreated immediately.