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Abatatsept

Per 2008 in the Russian Federation the genno-engineering biological preparation with other, in comparison with inhibitors FNO, the action mechanism - abatatsept is registered. It represents the soluble hybrid albuminous molecule consisting of the extracellular domain human CTLA4 (cytotoxic T - lymphocyte-associated antigen 4), linked with modified Fc (CH2 and CH3 areas) a fragment human IgG1 [81, 85, 116,118,121,144,145,149].

Abatatsept modulates key to-stimuljatornyj a signal which is required for full activation T-limfotsitov with eksperssirujushchimisja on them CD28. T-limfotsity are found out in sinovialnoj to a cover in patients with juvenilnym an arthritis. Activation T-limfotsitov are the important link of pathogenesis JUIA. For full activation T-limfotsitov 2 signals which are realised with participation an antigen prezentirujushchih cells (agrarian and industrial complex) are required: identification of a specific antigen by receptors of T-cages (1 signal); to - stimuljatornyj a signal which is provided at the expense of interaction of receptor CD28 on T-limfotsitah and CD80/CD86 on agrarian and industrial complex. Abatatsept specifically contacts CD80/CD86, inhibiting this to-stimuljatornyj a way therefore activation of T-cages is blocked, and accordingly all cascade of the subsequent immunologic reactions [145].

In clinical researches it is shown, that abatatsept in doses approximately 10 mg/kg inhibit activation T-limfotsitov, reduces production of macrophages, fibroblastopodobnyh sinoviotsitov and V-cages, and also suppresses an acute phase of a reactivation of an inflammation. Maintenance reduction in Serum of a soluble receptor SILT 2, an activation marker T - lymphocytes was observed; SILT 6, a product of activation of macrophages and fibroblastopodobnyh sinoviotsitov; the rhematoid factor, the antibodies produced by plasma cells; S-jet fiber. Reduction of serumal level matriksnoj metalloproteinazy-3 which causes a destruction of a cartilage and fabric structural changes was besides, observed. Also
Reduction of serumal maintenance FNOa [14,47,53,66,106,118,121,144,145,149] was observed.

In pediatric practice use Abatatsepta is authorised since six years for treatment of patients with polyarticulary variant JUIA. The preparation is prescribed in a dose of 10 mg/kg to introduction intravenously during 30 mines, repeated infusions are carried out in 2 and 4 weeks after the first, each 4 weeks further [24,25,45,46,48,85,86,119,121,149,152].

Efficiency abatatsepta is proved in a number of foreign and domestic researches, as for treatment RA of adults, and JUIA [1,5,8,20,81,89,107,108 110,111].

The most scale is randomizirovannoe double blind platsebokontroliruemoe efficiency and safety research abatatsepta, spent under the guidance of professor Ruperto N., which was spent in 45 medical centres. 190 children have entered into it at the age from 6 till 17 years with active JUIA with a lesion not less than five joints and an inefficiency of previous therapy by one and more basic illness - a modifying antirheumatic preparation. Abatatsept it was prescribed in a standard dosage. The open phase of research was finished by 170 patients (90 %), from them at 47 patients has not been taped signs of the positive clinical answer on ACR pedi, they have been excluded from research. To the termination of an open phase of research (in 4 months) 30 % improvement on ACR pedi has been registered at 123 (65 %) patients, 50 % - at 95 (50 %), 70 % - at 54 (28 %), 90 % at 24 (13 %) children.

Efficiency abatatsepta was various at children, before treated by inhibitors FNO, and not receiving the given therapy. So, from 57 children receiving in the anamnesis inhibitors FNO only at 22 (39 %) 30 % and more improvement by criteria ACR pedi has been noted. Unlike this group, of 133 children who were not treated by inhibitors the TNF and, the positive effect from therapy abatatseptom (ACR pedi 30 and more) has been reached at 101 (76 %) the child. Further, children with the positive clinical answer to therapy abatatseptom by criteria ACR pedi (122 children) were randomizirovany on 2

Groups: the basic group - 60 patients (children receiving abatatsept within 6 months or before occurrence by a sign of relapse of an arthritis), control group - 62 patients (children receiving within 6 months platsebo). The purpose of the given phase of research was comparison of an interval of time before development of an exacerbation in the patients treated abatatseptom and platsebo. In 6 months of therapy in group of children receiving abatatsept, ACR pedi 30 it has been registered at 82 % of patients, ACR pedi 50 at 77 %, ACR pedi70 at 53 %, ACR pedi 90 - at 40 %. In group platsebo indicators were worse: ACR pedi 30 at 69 % of patients, ACR pedi 50 at 52 %, ACR pedi70 at 31 %, ACR pedi 90 - at 16 %. Statistically authentic difference at comparison of results in two groups it has not been received. In group of children receiving platsebo, the answer to therapy was worse in comparison with a similar indicator at the moment of including in a double blind phase of research. The risk of occurrence of relapse of an arthritis at the patients receiving abatatsept, was less, than at the patients receiving platsebo (the relation it is brave 0-31, 95 % confidential intervals 0-16-0-95). Frequency of occurrence

Adverse collateral reactions it was comparable in both groups. Developments of the serious undesirable phenomena against preparation reception abatatsepta it has not been noted. By results of the carried out research it is possible to draw a conclusion on high efficiency and safety abatatsepta [81, 149].

In a number of the researches spent on population of patients with RA, the answer amplifying eventually to therapy abatatseptom is proved. So, in research AGREE, at patients with early RA, on the second year of therapy abatatseptom more essential retardation of radiological advance of disease, than on the first year is noted. Frequency of offensive of remission at the patients receiving treatment of 2 years, has increased from 46,1 % the first year prior to 55,2 % to the extremity of the second year of therapy. In research AIM of 72 % of the patients having the good answer to therapy abatatseptom to the extremity of the first year, have kept this answer up to 5 years of continuous treatment [118].

M.F.Dubko with co-authors has carried out the retrospective research the efficiency and safety estimation abatatsepta at children with JUIA became which purpose,
Earlier not receiving therapy GIBP. 20 patients have entered Into research at the age from 3 till 17 years. All patients had the big duration of disease (6,5 years), high indicators of clinico-laboratory activity of disease. In 8 months from the beginning of research of 70 % of patients have reached at least 30 % of improvement on criteria ACR pedi. From various subtypes JUIA the most sensitive to treatment had appeared a system variant (without system implications for a moment initsiatsii abatatseptom), on therapy have answered all 3 of 3 patients, and a polyarticulary variant where the answer on abatatsept is received at 9 of 11 persons. Among the reasons which have led to cancellation of therapy, absence of effect or insufficient efficiency - 4 children, nekomplaentnost - 1 child, collateral reactions (a headache, vomiting, a syncope, abdominal pains on 7th put after preparation introduction) - 1 child was the most frequent. [128].

In the research spent by Keltsevym V. A it has been proved, that the combined therapy abatatseptoi and Methotrexatum much more effective than monotherapy by Methotrexatum at treatment of children with polyarticulary variant JUIA. So, in 48 weeks from the research beginning, in group of the patients receiving combined therapy, at 35 % proof remission of a basic disease, and in group of children receiving monotherapy metotreskatom - only at 16 % of children [134] has been received.

In work Alekseevoj E.I.s of co-authors, efficiency abatatsepta is studied on 15 patients with polyarticulary variant JUIA. In 4 months from the beginning of research improvement by criteria ACR pedi 30/50 has been reached at 60/30 %; in 6 months ACR pedi 30/50/70 — at 80/40/40 %, accordingly; in 12 months ACR pedi 70 — at 80 % of patients. The status of inactive illness in 6 and 12 months is registered at 6/15 (40 %) and 10/15 (66 %) patients, accordingly, remission — at 10/15 (66 %) children in 12 months of treatment. The undesirable phenomena are noted at 6/15 (40 %) patients and characterised by easy severity level. At three patients the exacerbation of infection Herpes labialis took place, 3 children have transferred an acute respiratory infection [116].

Now in the literature a number of clinical examples proving high efficiency abatatsepta at children with a rhematoid uveitis [127,152] is described. According to Neroeva V.V. and co-authors, at appointment abatatsepta the patient with an active uveitis, in 5 from 18 cases (27,8 %) development of remission of a uveitis, still at 5 (27.8 %) - improvement became perceptible. However, at one child with JUIA, without a lesion of eyes for a moment initsiatsii abatatseptom, against treatment GIBP uveitis development is fixed. It is necessary to underline, that positive dynamics concerning a uveitis is noted only at 2 of 8 children (25 %), receiving earlier with insufficient efficiency inhibitors the TNF - and while at patients not receiving earlier GIBP, remission has come at 4 children (40 %), improvement - still at 4 (40 %) from 10 patients at comparable gravity of inflammatory process in both groups [148].

Summarising data of references, it is possible to speak about good shipping and a high profile of safety abatatsepta. So, in research Ruperto N. Frequency of development of the undesirable phenomena in group platsebo and abatatsepta was identical - at 55 % and 62 % of patients accordingly [81]. Undesirable reactions basically have been presented by postinfusional reactions (a headache, delicacy, a nausea etc.), the become frequent intercurrent infections.

Thus, the analysis of results of the spent clinical researches testifies to high efficiency and safety abatatsepta. The good answer to therapy has been received as at children with articulate variant JUIA, mainly with the polyarticulary form, and with a system variant, without extraarticular implications for a moment initsiatsii abatatseptom. Against long application abatatsepta it becomes perceptible increase of efficiency of therapy.

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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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Other medical related information Abatatsept:

  1. variants of therapy of an anaemia at chronic illnesses and their efficiency
  2. 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
  3. THE TABLE OF CONTENTS
  4. INTRODUCTION
  5. Abatatsept
  6. comparative efficiency and safety GIBP.
  7. Chapter 2. MATERIALS And METHODS.
  8. Chapter 3.1. Efficiency and safety infliksimaba at children with JUIA.
  9. Chapter 3.3. Efficiency and safety abatatsepta at children with JUIA.
  10. CHAPTER 4. EFFICIENCY AND SAFETY GIBP COMPARISON (INFLIKSIMABA, ETANERTSEPTA AND ABATATSEPTA) AT CHILDREN WITH JUIA.
  11. CHAPTER 4.1. Efficiency and safety GIBP comparison (infliksimaba, etanertsepta and abatatsepta) at children with system variant JUIA.