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CHAPTER №5 DISCUSSION

Now in an arsenal of the doctor-rheumatologist there is a considerable quantity of the various antirheumatic preparations used in treatment JUIA. “ The gold standard ”treatments of a pseudorheumatism and JUIA is Methotrexatum.

According to the literature, on the average, therapy by Methotrexatum is considered effective at 60-80 % of patients with JUIA. However, in group of children with polyarticulary and-or system variant JUIA percent of the patients answering therapy by Methotrexatum essentially more low, about 55 %. In this connection, there is a necessity for therapy intensifying by the second basic antirheumatic preparation and-or GIBP. On our data about 40 % of patients with polyarticulary variant JUIA and 56 % with system variant JUIA, despite massive standard antirheumatic therapy, require intensifying of therapy GIBP [162-163]. Considering extreme heterogeneity JUIA, a question on a choice of optimum strategy of treatment, selection of the most suitable preparation for each concrete patient, acutely rises before the practising doctor-rheumatologist.

During our research the efficiency and safety GIBP estimation (infliksimab, etanertsept, abatatset) at children with system and articulate variants JUIA is spent. The Research objective was place definition infliksimaba, etanertsepta, abatatsepta in algorithm of appointment GIBP at various variants JUIA. Feature of research was that all preparations were prescribed during the different periods of time that has affected characteristics of groups of the patients who have entered into research

Infliksimab - the first GIBP registered in the Russian Federation. Officially the preparation has not been resolved for use at children with JUIA. In our research infliksimab it was prescribed to children with the most serious current JUIA, torpid to massive basic immunosupreissivnoj therapies, under the permission of local ethical committee. 30 children have entered into research, from them 20 children (66,7 %) with system variant JUIA and 10 (33,3 %) with the articulate. Therapy infliksimabom was characterised by fast offensive of the answer on
Spent treatment. So, already after the first infusions of a preparation at children c JUIA the state of health considerably improved, expression of an articulate syndrome decreased, humoral activity of disease decreased. The greatest efficiency infliksimab has shown in treatment of children with poliartikurjarnym a variant of current JUIA. By 3rd months from the therapy beginning at least 50 % improvement by criteria ACR pedi has been received at all of 100 % by the patient. By 9 months at 77,8 % of patients against therapy infliksimabom proof clinico-laboratory medicamental remission JUIA (ACR pedi 90-100) has been reached. The obtained data are comparable to results published before researches [75,111,72-74]. So, in Alekseevoj E.I.'s work on the average in 1,5 months from the beginning of treatment at 69 sick (82,6 %) oligoartikuljarnym and at 41 patients (60,7 %) with a polyarticulary variant of disease infliksimab induced development of proof clinico-laboratory remission [72].

Less significant results have been received at treatment of children with system variant JUIA. Only at half of patients 50 % improvement by criteria ACR pedi have been received. At the remained half of children the answer to spent therapy that is obviously insufficient at treatment of a system variant of disease with high degree of clinico-laboratory activity has been received 30 percent and less.

Attracts attention gradual depression of efficiency of therapy infliksimaba eventually in connection with development secondary refrakternosti. However, at escalation of a dose of a preparation to 8-10 mg/kg on introduction, in the course of observation, it was possible to enlarge efficiency of spent therapy infliksimabom. Our data are comparable to the results received in work by Nikishinoj I.P. at children with system variant JUIA infliksimab it has appeared effective also only at 50 % of patients. Less significant results have been received in Alekseevoj E.I.'s work Where at 90 % of patients with system variant JUIA after the fourth-fifth introduction of a preparation the secondary inefficiency that was the reason for the treatment termination has developed.

At efficiency comparison infliksimaba at children with system and articulate variants JUIA, taking into account adherence to therapy, in our research had been received statistically authentic difference.

The undesirable phenomena as authentically met at children the system variant JUIA, receiving infliksimab is more often. Infusional reactions were the most frequent undesirable phenomena. However the reason of cancellation of therapy in the given sample infusional reaction became only at one child. In other cases the undesirable phenomena were quickly stopped by retardation of a rate of administering infliksimaba, intravenous introduction GK, appointment of antihistamine preparations. Among other undesirable phenomena development of a primary tubercular complex with centre localisation in the top share of the left lung which has been taped at the patient on 3rd year of successful application infliksimaba became the most serious. The information on development of tubercular process appeared in the literature and earlier. A number of researches proves rising of frequency of development of tubercular process both with pulmonary, and with vnelegochnymi implications of illness [76,22].

To the second GIBP appeared in the Russian Federation and found wide application in children's rheumatology became etanertsept. During our research efficiency and safety etanertsepta have been studied at 46 days, from them 16 children (33 %) with system variant JUIA and 32 (67 %) with the articulate. As a result of the carried out research high efficiency etanertsepta at children with articulate variant JUIA has been proved. By 6 months of treatment etanertseptom, at overwhelming number of patients (84,3 %) with articulate variant JUIA, the good answer to spent therapy (ACR pedi-50) has been received. Further, efficiency of therapy continued to accrue. By 24 months of research at 96,4 % of patients 70 % improvement by criteria ACR pedi have been received, and at third of patients proof clinico-laboratory remission has been reached. Seven children (21,9 %) managed to cancel basic immunosupressivnuju therapy and to continue monotherapy etanertseptom with the good answer. Less significant effect has been received at children with system variant JUIA. Only at
50 % of improvement on criteria ACR pedi were possible to reach half of patients. By results of research efficiency etanertsepta at children with articulate variant JUIA it is authentic above (on indexes LUNDEX) than at children with system variant JUIA (p 0,05). Similar results have been received in large research under the guidance of professor Ruperto N., where by 6 months at children mainly with articulate variant JUIA of 50 % improvement by criteria ACR pedi has been received in 77 % of cases, and 90 % improvement - at 40 % of children [142, 118].

On our data, against therapy abatatseptom efficiency increase was observed eventually, that repeatedly proved to be true in references [116-124].

Leaning against the international positive experience of application abatatsepta at patients with a rhematoid uveitis, in our research, in group abatatsepta, children with the given pathology have been included. During research depression of activity of pathological process from eyes so, already by 6 months of therapy, a uveitis exacerbation it was possible to stop in three cases (60 %) from five is noted. On the data published by employees of scientific research institute of eye illnesses by it. Gelmgoltsa, efficiency abatatsepta at patients with an active uveitis was little bit more low: only in 5 from 18 cases (27,8 %) uveitis remission, still at 5 (27,8 %) - improvement [107] is reached.

Therapy abatatseptom differed good shipping and high degree of safety. In a subgroup of children with system variant JUIA in one of observable cases development of the undesirable phenomena has not been noted. At children with articulate variant JUIA the safety profile abatatsepta was worse. At two children development of the undesirable phenomena (infusional reaction, gerpeticheskaja an infection) has led to preparation cancellation.

The good profile of safety abatatsepta is confirmed by a number of references [118-121, 142, 107]. 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. Undesirable reactions basically have been presented by infusional reactions (a headache, delicacy, a nausea etc.), the become frequent intercurrent infections [142].

During our research efficiency and safety comparison infliksimaba, etanertsepta and abatatsepta at children with system and articulate variants JUIA has been spent.

In a subgroup with system variant JUIA at comparison of efficiency of therapy GIBP taking into account adherence factor to therapy, by means of index LUNDEX, authentic differences between preparations it has not been received
(p> 0,05). The tendency of larger efficiency abatatsepta was traced. However, in group abatatsepta, children with smaller activity of disease, without extraarticular implications for a moment initsiatsii, unlike groups infliksimaba and etanertsepta have initially been included, that should be reflected in the received results. At comparison of frequency of the taped undesirable phenomena the conclusion that infliksimab possesses lower profile of safety in comparison with etanertseptom and abatatseptom has been drawn.

In a subgroup with articulate variant JUIA in 6 months from the beginning of therapy of 50 % improvement by criteria ACR pedi has been received more than at 70 % of children in all studied groups. Thus, in group infliksimaba the highest efficiency is taped: at all children 70 % improvement on ACR pedi became perceptible at least, and at half of children development of clinico-laboratory remission (ACR pedi 90,100) has been fixed. Frequency of development of remission against therapy etanertseptom and abatatseptom, in 6 months from initsiatsii, was authentically more low (r

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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 CHAPTER №5 DISCUSSION:

  1. CHAPTER 1. LITERARY DATA ON EARLY REVEALING OF THE TUBERCULOSIS AT CHILDREN AND TEENAGERS
  2. CHAPTER 2. THE CHARACTERISTIC OF THE SURVEYED PATIENTS AND APPLIED METHODS OF INSPECTION
  3. CHAPTER 3. OWN RESULTS
  4. CHAPTER 4. DISCUSSION
  5. Chapter 1 Modern representations about functional disturbances of a motility of organs of digestion (the literature review)
  6. Chapter 2 Materials and research methods
  7. Chapter 3 Results of own researches
  8. Chapter 4 Discussion of the received results
  9. Chapter 7 DISCUSSION of RESULTS of RESEARCH
  10. CHAPTER 8. THE CONCLUSION (DISCUSSION OF THE RECEIVED RESULTS)