CHAPTER 4.1. Efficiency and safety GIBP comparison (infliksimaba, etanertsepta and abatatsepta) at children with system variant JUIA.

38 children have entered into a subgroup with system variant JUIA. During work 44 clinical cases of application GIBP are surveyed. In connection with development of a secondary inefficiency infliksimaba 5 children have been translated from group infliksimaba in group etanertsepta, 1 child - in group abatatsepta where the efficiency and safety GIBP estimation (a drawing 4.1.1) has been continued.

Drawing №4.1.1. Distribution of patients in research depending on used GIBP.

Etanertsept 5 children Infliksimab 1 child Abatatsept

16 children ◄------------20 children ► 8 children

Groups infliksimaba and etanertsepta were comparable by quantity of studied clinical cases. The quantity of children with the system variant JUIA, receiving abatatsept, was much less, than in other groups. It is bound first of all to absence for a moment initsiatsii the saved up clinical experience of application abatatsepta at children with system variant JUIA, c absence of references for treatment of given variant JUIA abatatseptom, and further, from preparation occurrence totsilizumab in an arsenal of the doctor-rheumatologist.

All children in studied groups basically were comparable on age, a debut of disease, duration of current JUIA to initsiatsii GIBP. In group abatatsepta, in comparison with other groups, appreciable numerical prevalence of girls over boys (7:1) (table 4.1.1) became perceptible.

The table № 4.1.1. The comparative characteristic of the patients included in

Research with system variant JUIA.

** р=0,001, * r 0,05) (table 4.1.4, a drawing 4.1.3).

The table № 4.1.4. Comparison of efficiency GIBP in 12 months from the beginning of therapy at children with system variant JUIA.

Drawing № 4.1.3. Comparison of efficiency GIBP at children with system variant JUIA in 12 months from the therapy beginning.

In 12 months from the beginning of research adherence to therapy in group abatatsepta was peer 1. In group infliksimaba this indicator was above - 0,9, in comparison with group etanertsepta - 0,75, despite lower efficiency infliksimaba. It is bound by that after 6 months from the therapy beginning etanertseptom, four children with low efficiency have been translated on therapy totsilizumabom. Earlier these patients with classical system variant JUIA have appeared "neotvetchikami" on therapy infliksimabom. In turn, patients from group infliksimaba, with the low answer to therapy in 12 months from initsiatsii, had no possibility of transition to another gennoyoinzhenernuju therapy, because of absence of others GIBP. In this connection, attempt of escalation of a dose infliksimaba without preparation cancellation has been made. Considering all aforesaid, we cannot bind size of factor of adherence to therapy exclusively to efficiency and safety of this or that preparation in the given concrete case. For the same reasons, comparison of indexes LUNDEX as will be not absolutely correct. However, at use of the given index, it is taped statistically authentic difference in frequency of occurrence of 50 % of improvement between groups infliksimaba and abatatsepta (р=0,001). As, in group abatatsepta 80 % the answer by criteria ACR pedi in comparison with groups etanertsepta and infliksimaba (р=0,001) (table 4.1.5, a drawing 4.1.4) authentically have been more often received.

The table № 4.1.5. Indicators of indexes LUNDEX at children with the system

Variant JUIA against therapy GIBP in 12 months from initsiatsii.

Drawing № 4.1.4. Indicators of indexes LUNDEX at children with system variant JUIA against therapy GIBP in 12 months from initsiatsii.

By 18 months from the therapy beginning to estimate efficiency and safety GIBP it was possible only at 27 patients. The others 17 have left research on different terms, as a rule, because of an inefficiency of spent therapy.

At comparison of efficiency of therapy by criteria ACR pedi 50, authentic differences between groups it has not been received. However, at comparison of frequency of occurrence of 70 % of improvement, higher efficiency has shown abatatsept (p> 0,05). In this group of children ACR pedi 70 it is registered at 80 % of children. In turn, disease remissions did not manage to be reached to any child, among those who was on therapy abatatseptom.

In group etanertsepta the good answer to therapy (ACR pedi 70) has been received at 55,6 % of children, at 33 % development proof klinikoyolaboratornoj medicamental remission is fixed.

The answer to therapy infliksimabom has appeared less significant. By 18 months from the therapy beginning, despite escalation of a dose of a preparation, only at 38,5 % of children 70 % improvement by criteria ACR pedi have been received, that essentially differs from results in other groups. However, just as in group etanertsepta, at 30,8 % of children, to this term, proof medicamental clinico-laboratory remission (table 4.1.6, a drawing 4.1.5) has been received.

Statistically authentic difference in efficiency, by criteria ACR pedi, between investigated groups, in 18 months from initsiatsii GIBP, it has not been received (> 0,05).

The table № 4.1.6. Comparison of efficiency GIBP by criteria ACR pedi in 18 months from initsiatsii at children with system variant JUIA.

Drawing № 4.1.5. Comparison of efficiency GIBP by criteria ACR pedi

In 18 months from initsiatsii at children with system variant JUIA.

The adherence factor to therapy in 18 months for infliksimaba has made 0,72, for etanertsepta - 0,56, for abatatsepta - 0,714. Indicators of index LUNDEX are presented in table №4.1.7 and in a drawing 4.1.6.

The table № 4.1.7. Indicators of indexes LUNDEX at children with the system

Variant JUIA against therapy GIBP in 18 months from initsiatsii.

Drawing № 4.1.6. Indicators of indexes LUNDEX at children with the system

Variant JUIA against therapy GIBP in 18 months from initsiatsii.

At comparison of efficiency of therapy GIBP taking into account adherence factor to therapy, by means of index LUNDEX, in 18 months from the beginning of research, authentic differences in studied groups as it has not been received (p> 0,05). The tendency of larger efficiency abatatsepta is traced. However, in group abatatsepta, children with smaller activity of disease, without extraarticular implications for a moment initsiatsii, unlike other groups that should be reflected on have initially been included

The received results.

Against therapy GIBP at a part of children it was possible to cancel those or other basic antirheumatic preparations, to lower a dose metilprednozolona per os. So, by a year of therapy, in group infliksimaba it was possible to lower daily average dosage GK per osпо to Prednisolonum with 6,2 yo 3,6 (6,0) mg to 3,08 ±2,4 (2,9) mg, in group etanertsepta - with 5,6 yo 2,3 (5,2) mg to 3,0 ±1,5 (3,0) mg. In group abatatsepta, by 18 months from initsiatsii, only one girl continued to receive Prednisolonum per osв to a daily average dosage of 0,05 mg/kg. As, in all groups of observation, against therapy GIBP, it was possible to lower considerably frequency of carrying out of intraarticulate punctures with introduction GK

In the table № 4.1.8 summary data on a profile of safety GIBP at children with system variant JUIA are presented. The greatest profile of safety by results of the carried out research possessed etanertsept and abatatsept. At their long use development of the serious undesirable phenomena has not been registered. However, against therapy etanertsepta, in 8 months from initsiatsii, at one child the bilateral rhematoid uveitis for the first time has been taped. Worse the situation was with infliksimabom. The undesirable phenomena on preparation introduction infliksimab consisted in development of infusional reactions at 5 of 20 patients (20 %) in the form of vascular reactions, a cyanosis, difficulty of breath, a nausea. At one child infusional reaction became the reason of cancellation of a preparation. Still one girl on the first introductions of a preparation had allergic enanthesises. 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. At 2 patients receiving therapy infliksimabom, the infection caused by virus Herpes Zoster is fixed.

The table № 4.1.8. The undesirable phenomena against therapy GIBP at children with

System variant JUIA.

The primary tubercular

Complex on 3th year 1 (cancellation

Therapies GIBP of a preparation)

Proceeding from the aforesaid it is possible to draw a conclusion that infliksimab possesses lower profile of safety in comparison with etanertseptom and abatatseptom.

The carried out research allows to draw a conclusion that at children with system variant JUIA therapy infliksimabom and etanertseptom has appeared effective (> ACR pedi50) only at 50 % of children that is insufficient for patients with the given variant of disease. In group of children abatatsepta, at activity of disease no more the second degree and in the absence of system implications JUIA for a moment initsiatsii, therapy has appeared effective at 60 % of children (ACR pedi 50,70).