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INTRODUCTION

Theme urgency.

JUvenilnyj the idiopathic arthritis (JUIA) is chronic, immunovospalitelnoe, progressing disease of children and teenagers with a primary lesion of joints of an obscure aetiology and a difficult pathogenesis which leads to a gradual destruction of joints, is quite often accompanied by extraarticular implications, breaks growth of the child, negatively influences quality of a life of children.

According to modern data, the case rate fluctuates from 2 to 16 persons on 100000 children's population, is elderly till 16 years. Prevalence JUIA in the different countries makes from 0,05 to 0,6 % among the children's population. The disease aetiology up to the end is not studied, that does impossible primary preventive maintenance and the etiotropic approach to therapy JUIA. Treatment JUIA remains to one of the most difficult and actual problems of children's rheumatology.

In therapy JUIA the wide spectrum of antirheumatic preparations and their combinations is used: nonsteroid antiinflammatory preparations (NPVP), glucocorticoids (GK) for peroral, intravenous and intraarticulate introduction, hinolinovye derivatives, D-penitsillamin, an immunoglobulin human normal, gold preparations, Sulfasalazinum (SSZ), leflunomid, immunosupressanty from groups: tsitostatikov (cyclophosphamide, Azathioprinum, hlorambutsil), antimetabolites (Methotrexatum) and selective immunosupressanty (cyclosporine). All listed various on chemical structure and pharmacological properties medical products concern "pathogenetic". They are united by ability to a greater or lesser extent at the expense of various mechanisms to suppress immunoagressivnyj process at JUIA. Antirheumatic illness-modifying therapy (BPVP) at the majority of patients with JUIA stops or reduces activity of disease, improves quality of their life. However at a part of patients BPVP do not allow to reach the proof remission, some patients badly transfers basic preparations. Remaining
Activity, disease advance, threat of an invalidism of such patients defines necessity of introduction of new approaches to pathogenetic therapy JUIA.

Now in treatment JUIA the appreciable successes bound first of all with working out of a new class of preparations are reached, possessing ability specifically to block the important links immunopatogeneza diseases which have received the general name gennoyoinzhenernye biological preparations (GIBP). Inhibitors of the factor of a necrosis concern them tumours (TNF) - an alpha (infliksimab, adalimumab, etanertsept), anti-in-cellular preparations (rituksimab), blockers to-stimulation T - lymphocytes (abatatsept), a receptor blocker interlejkina-6 (ИЛ-6) -

totsilizumab. By data randomizirovannyh platsebo-supervised researches (RPKI), spent at patients with a pseudorheumatism (RA) and JUIA, GIBP surpass in efficiency Methotrexatum which is surveyed as the gold standard pharmacotherapies of given diseases BPVP.

The basic problem which rheumatology nurseries now face at a choice of therapy JUIA, absence of straight lines (head-to head) comparative controllable researches of efficiency and safety various GIBP is.

In this connection comparison of efficiency and safety GIBP, such as infliksimab, etanertsept, abatatsept, is an actual problem of children's rheumatology.

Research objective - place Definition infliksimaba, etanertsepta, abatatsepta in algorithm of appointment GIBP at various variants JUIA.

Research problems:

1.

To carry out the analysis demographic, clinico-immunologicheskih features of patients with JUIA, torpid to standard antirheumatic therapy.

2. To estimate efficiency and safety infliksimaba in complex treatment of various variants JUIA.

3. To estimate efficiency and safety etanertsepta in complex treatment of various variants JUIA.

4. To estimate efficiency and safety abatatsepta in complex treatment of various variants JUIA.

5. To spend a comparative estimation of efficiency and safety GIBP (infliksimaba, etanertsepta, abatatsepta) at treatment of various variants JUIA.

6. To analyse dynamics of clinico-laboratory indicators and quality of a life of patients with JUIA depending on spent therapy.

Scientific novelty

For the first time in pediatrics the efficiency estimation is spent to safety GIBP with the different mechanism of action at treatment of children with JUIA. The comparative estimation of efficiency infliksimaba, etanertsepta, abatatsepta is spent at system and articulate variants JUIA in dynamics of observation from 6 till 24 months. For the first time the comparative estimation of safety of use GIBP is spent; indications and advantages of use of this or that preparation depending on the form and variant JUIA are defined.

The practical importance

The efficiency and safety GIBP estimation (infliksimab, etanertsept, abatatsept) at children with JUIA is spent. The place of everyone GIBP (infliksimab, etanertsept, abatatsept) in algorithm of treatment of children with various variants JUIA is defined.

The substantive provisions which are taken out on protection:

1. At 40 % of patients with articulate variant JUIA (polyarthritis) and at 56 % with system variant JUIA, despite massive standard antirheumatic therapy, necessity of therapy GIBP is taped. By 6-12 months from the beginning of application GIBP (infliksimaba, etanertsepta, abatatsepta) at 100 % of children with articulate variants JUIA and at 50 % with system variant JUIA it is possible to reach authentic klinikoyolaboratornogo improvements.

2. At children with system variant JUIA therapy infliksimabom and etanertseptom has appeared effective (> ACR pedi50) only at 50 % of children. In group of children abatatsepta, at activity of disease no more the second and in the absence of system implications JUIA for a moment initsiatsii, therapy has appeared effective at 60 % of children (ACR pedi 50,70).

3. At children with articulate variant JUIA efficiency of studied preparations has appeared above. So, by 6 months from the research beginning, more than at 70 % of children from all groups 50 % improvement by criteria ACR pedi have been received at least. By 24 months, taking into account adherence to therapy (on

I. Lundex), in groups infliksimaba, etanertsepta and abatatsepta answer ACR pedi has been received at 80 %, 94 % and 60 % of patients accordingly, in groups etanertsepta and abatatsepta clinico-laboratory remission has been reached at 40 % of children.

4. By-effects authentically met in group infliksimaba is more often and included infusional reactions, the secondary virus and bacteriemic infections which have led to cancellation of a preparation.

Introduction of results of work in practice

Dissertation substantive provisions are introduced in practical work of specialised children's rheumatological unit of the University children's hospital of the First MGMU of I.M.Sechenova.

Work approbation

Dissertation materials are stated at annual conferences “Perfection of pediatric practice. From simple to difficult”, 2013г., PReS 2011, PReS 2013, PReS 2014, EULAR 2012, EULAR 2013, on faculty meeting of children's illnesses of the first MGMU of I.M.Sechenova on May, 7th 2014г.

The personal contribution of the author

The author posesses the leading part in a choice of a direction of research, the analysis, generalisation and a scientific substantiation of the received results. The author personally analyses all histories of illnesses of the patients included in research, the estimation of an articulate syndrome, humoral activity JUIA, proanketirovany doctors, and patients on YOURS, patients and their parents on questionnaires CHAQ is spent. In the works executed in the co-authorship, the author personally spends modelling of processes, monitoring of key parametres, analytical and statistical processing, a scientific substantiation and generalisation of the received results. The contribution of the author is defining and consists in immediate participation at investigation phases: from statement of problems and their clinical realisation before discussion of results in scientific publications and reports and their introductions in practice.

Conformity of the dissertation to the passport of a scientific speciality

Scientific positions of the dissertation correspond to the formula of a speciality 14.01.08 - "pediatrics". Results of the carried out research correspond to area of research of a speciality, is concrete to points 2 and 3 passports of the pediatrist.

Publications

Dissertation materials are reflected in 18 printing works, including 8 in the reviewed scientific magazines recommended VAK the Russian Federation.

Volume and dissertation structure:

The dissertation is stated on 190 pages of the computer text, illustrated by 55 tables and 59 drawings and includes introduction, the literature review, the characteristic of the surveyed patients and the description of methods
Researches, 2 heads of results of own research, the conclusion, 3 clinical examples, conclusions, practical references, the list of the literature including 50 domestic and 112 foreign sources.

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Scientific source Loskutova Olga Jurevna. Efficiency and safety of genno-engineering biological preparations (infliksimab, etanertsept, abatatsept) at children with various variants juvenilnogo an idiopathic arthritis. The DISSERTATION on competition of a scientific degree of the candidate of medical sciences. Moscow - 2014. 2014

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