Lege Artis Medicinae

[Clinical pharmacologic principles and problems related to the clinical use of innovative and similar biological medicines]

KERPEL-FRONIUS Sándor

AUGUST 20, 2010

Lege Artis Medicinae - 2010;20(08)

[The active substances in the biological medicinal products are macromolecules, primarily proteins most of which are currently produced by various biotechnological methods in different biological systems. The spatial structure of the macromolecular active substances cannot be accurately determined by the presently available methods. Therefore, both physico-chemical and biological methods are needed for the control of their quality and production. The active proteins induce immunologic reactions in the organism. The appearance of neutralizing antibodies frequently leads to the inhibition of the effect of the biological medicines. The European Medicines Agency (EMA) registers the medicinal products containing similar macromolecular active substances produced by biotechnological methods as biosimilar agents, since their chemical identity cannot be proven. The similarities and differences of their biological and immunological effects can be evaluated only in comparative non-clinical and clinical trials. The frequent exchange of biological medicines increases the appearance of antibodies in the patients, therefore the substitution of biological drugs should be done only by the treating physicians if clinically necessary.]

COMMENTS

0 comments

Further articles in this publication

Lege Artis Medicinae

[The 15th conference of the European Hematology Association - Barcelona, June 10-13rd, 2010]

LIPTÁK Judit

Lege Artis Medicinae

[On the safety of angiotensin-receptor blockers - A new attack on this drug class]

FARSANG Csaba

[Up until now, angiotensin-receptor blockers have been considered to be the safest cardio-, cerebro-, reno- and vasculoprotective drugs. In a previous metaanalysis, ARBs were accused of increasing the risk of myocardial infarction, but a number of metaanalyses and randomised, controlled trials have disproved this hypothesis. In a recent metaanalysis, ARBs were associated with an increased risk of tumours. The author reviews this issue, discusses the flaws of the above metaanalysis and, on the basis of the most up-to-date data in the literature, expert opinions and official statements (FDA, EMA), concludes that members of this drug class should continue to be used according to their approved indications, which is supported by their cardio-, reno-, cerebro- and vasculoprotective effects demonstrated in a number of appropriate, large-scale clinical studies.]

Lege Artis Medicinae

[Need-adjusted inequalities in the use of healthcare in Hungary]

VITRAI József, BAKACS Márta, KAPOSVÁRI Csilla, NÉMETH Renáta

[INTRODUCTION - The reduction of need-adjusted inequalities in the use of healthcare results in higher efficiency and fairer allocation of resources. PATIENTS AND METHODS - Data for all patients who received inpatient care (same-day or hospital treatment) in 2007 were used in the analysis. Beyond the diagnostic and diagnosisrelated group’s weight information and the number of inpatient days, the patients’ record contained data on age, sex, and postal code of residency. Besides personal data, socio-economic characteristics and general indicators of healthcare capacity have been included in the applied multilevel statistical analysis. Inequalities were estimated for all patients, and separately for those treated for malignant tumour, cardio-vascular diseases, or other diseases. RESULTS - Significant regional inequalities were observed in one-day care but an order of magnitude less in longer inpatient care. Comparing the two major diagnostic groups, the inequalities were greater among patients with cardiovascular diseases than for those with cancer. Only a small fraction of the observed inequalities was explained by the differences in the composition of population of small regions. The inequalities in the use of healthcare were largely explained by socio-economic characteristics of the regions. CONCLUSIONS - Need-adjusted inequalities in the use of healthcare supported the hypothesis that efficiency of the Hungarian healthcare system can be significantly improved by allocating the available resources according to the patients’ need.]

Lege Artis Medicinae

[Tracking the Forgotten Profession]

NAGY Zsuzsanna

Lege Artis Medicinae

[Modern beta-blocker therapy from the cardiologist’s viewpoint]

ÉDES István

[Following the publication of some large, randomised trials (LIFE, ASCOT), the benefits of the use of beta-blockers in hypertension have been questioned. On the basis of these clinical trials it has been posited that beta-blockers administered for the treatment of hypertonia are less effecient for stroke prevention. It has been suggested that first-generation beta-blockers (atenolol) have adverse metabolic effects (insulin sensitivity, lipid parameteres), which might contribute to the differences observed in clinical outcomes. On the basis of a number of clinical trials and meta-analyses performed in recent years it is now evident that the most important goal is to reach target blood pressure levels, which is usually achieved by combination therapy. Choosing drugs on the basis of strict protocols is less important. In general, beta-blockers remain one of the most important drug class for the treatment of hypertension. The author reviews the pharmacology of the cardioselective, vasodilatory drug nebivolol in detail, as well as clinical trials on nebivolol. Nebivolol has a neutral (or rather beneficial) effect on metabolic parameters (lipid parameters, blood glucose level and insulin sensitivity) as well as on left ventricular function. If hypertension is associated with cardiovascular diseases (left ventricular dysfunction, ischaemic hears disease, atrial fibrillation), nebivolol offers an excellent therapeutic alternative due to its excellent tolerability and side effect profile.]

All articles in the issue

Related contents

Lege Artis Medicinae

[Tumor necrosis factor-alpha blockade: adverse clinical consequences and safety issues]

MŰZES Györgyi

[The pleiotropic cytokine tumor necrosis factor (TNF)-α seems to be fundamentally involved in the pathogenesis of a variety of immune-mediated (partly autoimmune) chronic inflammatory disorders; therefore, its blockade has allowed a remarkable advance in treatment strategies. Safety and tolerability profile of TNF-antagonists is generally favorable, their overall risk/benefit ratio is definitely positive. Possible adverse consequences related to TNF-α blocking monoclonal antibodies and soluble receptors can be classified as class-specific side effects that are related to their mode of action, and individual, molecule-specific effects. Immunogenic potential of immunoglobulins (Ig) eliciting an anti-(Ig-) antibody immune response may reduce or eliminate their therapeutic benefit, increase the risk of resistance or intolerance to biologic agents, and also lead to other adverse clinical effects. The immunogenicity profile of TNFantagonists is mainly related to their hetero- (xeno-), allo- (iso-)genic or idiotypic antigen character. By means of generating fully human monoclonal antibodies, more tolerable drugs could be introduced into clinical practice.]

Hypertension and nephrology

[Biosimilar erythropoesis stimulating agents - from registration to clinical practice]

KISS István

[The original patent drugs appear immediately on expiry of all rights in generic and biosimilar drugs in the pharmaceutical market, favorable supply option which helps in the rational management of medicines, mainly for generic drugs cheaper to allow more patient care. Of course, this is a well-organized legal and regulatory framework, thoughtful strategy can be successful in every respect. In another non-identical molecular structure biosimilar drugs in different immunogenicity of knowledge and risk is not defined in clinical practice and therefore the risk is still underestimated and not well regulated in the world, and increasing the number reported is the antibody formation case of a biosimilar erythropioetin also. The immunogenicity of original biological and of biosimilar drugs in identifying, defining a prominent role in the post-marketing surveillance, pharmacovigilance, and the special methods of control of immunogenicity. The original and the biosimilar medicines interchangeability, marketability of the assets relating to the regulations are not uniform in Europe or the European registration scheme is an important new biosimilar medicinal products, is that the medicinal product, the documentation is not expected to be accompanied by a risk management plan, as well as action to ensure the safety (pharmacovigilance) as part of the collection and reporting of adverse reactions to the official. It is important that the professional management of renal anemia guidelines - the practice of nephrology erythropoietin therapy - clearly define the biological medicines (originator and biosimilar erythropoietin) application requirements and suggestions. Consequently, this summary wants to draw attention to the therapeutic potential of biosimilar drugs, generic drugs to distinguish between explicit and the potential risks and the need to reduce the risks of professional and health policy decisions.]

Lege Artis Medicinae

[Therapeutic strategies in rheumatoid arthritis]

VÁNCSA Andrea, SZEKANECZ Zoltán

[In this review, we follow the consecutive steps of the internationally accepted therapeutic strategy of rheumatoid arthritis (RA). We summarise in brief the current European recommendations, and provide some advice on methotrexate (MTX) therapy. The initiation, maintenance and, if needed, switch of biological therapy is also discussed. Having reached remission or low disease activity (LDA), tapering or discontinuation of biologics may be considered. Finally, we review the possibilities and the most important biomarkers of personalised treatment.]