Chapter 3.2. Efficiency and safety etanertsepta at children with JUIA.

The efficiency and safety estimation etanertsepta was spent at 48 children with JUIA. From them 16 children (33 %) with system variant JUIA and 32 (67 %) with the articulate.

SYSTEM VARIANT JUIA:

In a subgroup of children with system variant JUIA из16 children there were 9 girls, 7 boys, middle age has made 10,7 yo 3,3 (9,8), from 3 till 17 years, the disease debut fell 3,06 yo 2,0 (4) years, average duration of disease before appointment etanertsepta - 8,0 yo 3,1 (8) (table 3.2.1).

The analysis of features of the beginning of disease has shown, that extraarticular implications, such as a fever, a lymphadenopathy, gepatosplenomegalija, an eruption, were observed at all patients, less often, at 5 sick (31 %), was taped mioperikardit. As, at all children in a disease debut became perceptible substantial increase of level of an ESR on the average to 47±17,1 (50) mm/ch, the expressed thrombocytosis - 463 yo 240 (490) ^h109/l, at 15 (93,8 %) children - a leukocytosis 12,5 yo 4,8 (13) ^h109/l, at one patient with syndrome Felti - a leukopenia of 3 ^h109/l.

By the appointment moment etanertsepta extraarticular implications remained only at 2 (12,5 %) patients in a kind gepatosplenomegalii, lymphadenopathies, a subfebrile fever. At the others 14 patients (87,5 %) extraarticular implications have not been noted.

In a disease debut proof the joint syndrome was observed at 12 (75 %) children. Thus, at 11 from them, the polyarthritis, and only at one child - oligoartrit at once was generated. At other 4 patients (25 %) in a disease debut flying arthralgias were observed, and proof the joint syndrome was generated by 6-18 months from the disease beginning.

Table 3.2.1. The General characteristic of patients with system variant JUIA against therapy etanertseptom, included in research.

All children before appointment etanertsepta received massive basic immunosupressivnuju therapy 2-mja and more preparations.

By the appointment moment etanertsepta 12 children (75 %) continued to receive GK per osв to a daily average dosage on Prednisolonum 5,6 yo 2,3 (5,2) mg a day. Four children (25,0 %) were on monotherapy by Methotrexatum of 10-15 mg/m². Other children received combined immunosupressivnuju therapy.

The quantity of active joints before therapy etanertseptom on the average made 21,6 yo 15 (20), joints with function restriction - 29,0 yo 14 (25).

Before appointment etanertsepta all children were with high (III) degree of laboratory activity of disease. An ESR on the average made 36 yo 16 (40) mm/ch, SRB - 5,6 yo 5,0 (5,2) mg/dl. At the overwhelming majority of patients rising of immunoglobulins G (1682 yo 472 also was observed (1740) the mg/dl), is more rare than M immunoglobulins, rising of level of thrombocytes - 435 yo 145 (460) ^h109/l, leucocytes - 10,0 yo 3,5 (10,4) ^h109/l. The Russian Federations and ANF have not been taped in one of cases. As, at children depression of level of serumal haemoglobin - 106 yo 25 (100) mg/dl became perceptible.

The general estimation the doctor of activity of illness on YOURS made 85,9 yo 15,6 (100) points, the estimation the patient and-or his parent was hardly more low - 75,8 ±15,5 (90) points.

Functional insufficiency of patients by criteria CHAQ before appointment etanertsepta has on the average made 2,07 yo 0,6 (2,4) points, that on classification Dempster and co-authors there corresponds to serious functional disturbances (table 3.2.1).

EFFICIENCY ETANERTSEPTA AT CHILDREN WITH SYSTEM VARIANT JUIA:

Later 6 months from the therapy beginning etanertseptom, are noted appreciable depression of quantity of active joints with 21,6 yo 15 (20) to 11,7 yo 14,0 (10) and joints with restriction of function with 29 yo 14 (25) to 25 yo 17 (22) (table 3.2.3, a drawing 3.2.1).

Drawing № 3.2.1. Dynamics of quantity of active joints and joints with restriction of function at children with system variant JUIA against therapy etanertseptom.

As, in studied group of children, depression of humoral activity has been noted at 11 patients, activity of disease remained with the others enough high. ESR average indexes in dynamics - 23,6 yo 12 (20) mm/ch (before therapy 36 yo 16 (40) mm/ch) (р=0,019), SRB 3,8 yo 5,5 (3,5) mg/dl (before therapy 5,6 yo 5,0 (5,2) mg/dl) (р=0,340). Haemoglobin level remained practically without change, and has made 108 yo 21 (110) mg/dl. The quantity of leucocytes has decreased and has made 8,9±2,8 (9,0) ^h109/l, thrombocytes - 386 yo 123 (360) ^h109/l, immunoglobulins G - 1558±491 (1500) mg/dl (a drawing 3.2.2).

Drawing № 3.2.2. Dynamics of an ESR at children with system variant JUIA against therapy etanertseptom.

The general estimation the doctor of activity of illness on YOURS has decreased to 54,6 yo 37 (50) points (р=0,004), an estimation the patient and-or his parent - to 48 ±18 (42) points (0,001). Functional insufficiency of patients in 6 months from the therapy beginning has made 1,18 yo 0,9 (1,0) points (р=0,003) (a drawing 3.2.3).

Drawing 3.2.3. Dynamics of indicators YOURS of the doctor and patients and-or their parents at children with system variant JUIA against therapy etanertseptom.

Drawing № 3.2.4 Dynamics CHAQ at children with system variant JUIA against therapy etanertseptom.

At a complex estimation of efficiency etanertsepta at children with system variant JUIA, refractory to standard antirheumatic therapy, ACR pedi-30 has been reached at 13 children (81,25 %), ACR pedi-50 - at 11 (68,75 %), ACR pedi-70 - at 4 (25 %), ACR pedi-80 - at one child (6,25 %). One girl, from 50 % the answer, in 6 months from the therapy beginning has independently cancelled leflunomid, continuing to receive Methylprednisolonum in a dose of 0,1 mg/kg/sut and etanertsept in an age dosage (by 12 months 70 % of improvement have been reached). To One more boy from 70 % by the answer have been cancelled leflunomid and Methylprednisolonum, the child continued to receive Methotrexatum of 10 mg/m² and etanertsept with good effect. To two more children, from 70 % the answer by criteria ACR pedi, it was possible to cancel completely Methylprednisolonum per os (a drawing 3.2.5, table 3.2.4).

Therapy etanertseptom has appeared noneffective at 3 children (18,8 %), nizkoeffektivnoj (only ACR pedi-30) - at two children (12,5 %). At these patients with classical system variant JUIA earlier it was not observed the answer to therapy infliksimabom. Further, four from these children have been translated on therapy totsillizumabom.

Later 12 months from the beginning of therapy efficiency etanertsepta was estimated at 12 patients. The quantity of active joints and joints with function restriction continued to decrease to 5 yo 3 (5) and 20 yo 15 (18) accordingly. The further depression of humoral activity has been received at 9 children. The ESR average index has decreased on the average to 18,2 yo 11 (19) mm/ch, SRB - 1,7 yo 4,0 (1,5) mg/dl (0 and 12 months). The quantity of leucocytes has decreased to 7,6±2,3 (8,0) ^h109/l, level of thrombocytes - 288±71 (250) ^h109/l (norm) has considerably decreased. Indicators of immunoglobulins remained at former level. Normalisation of level of haemoglobin in blood - 123 yo 17 (130) mg/dl (a drawing 3) became perceptible

YOUR indicator of the doctor has decreased to 50 yo 11 (46), YOURS of the patient and-or the parent - to 21 yo 10 (20) points. Functional insufficiency of patients in 12 months from the therapy beginning has made 0,875 yo 0,65 (0,7) points that corresponds to the minimum functional disturbances on classification Dempster (a drawing 3)

At all children absence of advance of erosive changes in joints is noted. According to radiological inspection, at one child disappearance before the taped erosions of articulate surfaces is noted.

At a complex estimation later 12 months in group of patients with system variant JUIA ACR pedi-50 will reach at 9 children (75 %), ACR pedi-70 - at 6 (50 %), ACR pedi-80 at 1 (8,3 %). At 3 children (25 %) low efficiency of spent therapy remained. These children as have been translated on therapy totsillizumabom (a drawing 3.2.5, table 3.2.3).

It is necessary to notice, that by a year of therapy etanertseptom, it was possible to lower a daily average dosage of Methylprednisolonum per osс 5,6 yo 2,3 (5,2) mg to 3,0 yo 1,5 (3,0) mg, and still to 2nd children completely to cancel a preparation. To one more girl, from 50 % improvement, it was possible to cancel Sulfasalazinum, because of bad shipping of a preparation. Further, the girl had been continued therapy by Methylprednisolonum per os0,05 mg/kg and etanertseptom 0,4 mg on introduction with good effect.

By 18 months of research, among remained 9 patients continuing treatment etanertseptom, the quantity of active joints has decreased to 2 yo 2,5 (1,5), joints with function restriction - 19 yo 17,8 (18). At 8 children
The further depression of immunologic and humoral activity became perceptible: an ESR - 12 yo 7,8 (10) mm/ch, SRB - 0,7 yo 1,1 (0,4) mg/dl. The quantity of leucocytes, thrombocytes, immunoglobulins, level of haemoglobin of blood remained without essential dynamics in comparison with 12-month's measurements. YOURS of the doctor (45 yo 14 (42) points) and YOURS of the patient and-or the parent (20 yo 10 (20) points), level of functional insufficiency (0,75 yo 0,65 (0,6) points) - without essential dynamics.

At complex estimation ACR pedi-50 has been reached at 8 children (89,0 %), ACR pedi-70 - at 5 (55,6 %). ACR pedi-80 - at 4 (45 %). At 3 children pharmacological clinico-laboratory remission of disease has been reached: ACR pedi-90 at 3 (33,3 %), ACR pedi-100 - at 1 (11 %). At one child the aggravation of symptoms, efficiency etanertsepta, on the contrary, became perceptible has decreased from 70 % to 30 % of the answer. In this connection, the child has been translated on therapy totsillizumabom (a drawing 3.2.5, table 3.2.3).

The adherence indicator to therapy etanertseptom at children with system variant JUIA after 12 months has made 0,75, and in 18 months - 0,56. Value of indexes LUNDEX to ACR pedi are presented in table №3.2.2

The table № 3.2.2. Index LUNDEX at children with system variant JUIA against therapy etanertseptom.

In a subgroup of children with system variant JUIA throughout 6 months of observation at 2 children at therapy discontinuing etanertseptom it is registered
The exacerbation of a basic disease accompanied both increase of an articulate syndrome, and extraarticular implications (a fever, a carditis, a leukocytosis, a thrombocytosis). After therapy renewal etanertseptom positive dynamics became perceptible: extraarticular implications were stopped, humoral activity has decreased. However, at one of these children, in 8 months from initsiatsii etanertseptom, the bilateral uveitis in a stage of incomplete remission for the first time has been diagnosed. To treatment topical steroids have been added by a short course, therapy etanertseptom has been continued. By 12 months from initsiatsii etanertseptom it was possible to reach full remission of a uveitis, by criteria ACR pedi, 70 % improvement have been received. At other 14 patients of the exacerbations accompanied by extraarticular implications, for all period of observation it has not been noted.

During research, in one of clinical cases, it has not been noted developments of the undesirable phenomena which have led to cancellation of a preparation. At two children, on the first 3 introductions of a preparation occurrence of a local moderate hyperemia in an injection place has been noted. At one child as already it has been told earlier, in 8 months from initsiatsii, uveitis development de novo is registered.

Thus, by 18 months, only at 8 of initially included 16 in research of children (50 %) therapy etanertseptom has appeared effective (achievement at least ACR pedi-50). The others 8 children, in connection with insufficient efficiency of therapy etanertseptom, in different terms of observation have been translated on therapy totsilizumabom. However, among 9 children who have remained in research in 18 months from the beginning of therapy of 50 % improvement it has been received at 89,0 % of patients, clinico-laboratory remission - at 33,3 %. These indicators is high enough, and prove appointment possibility etanertsepta to children with system variant JUIA, without system implications for a moment initsiatsii. Etanertsept possesses a good profile of safety. However, therapy discontinuing, at children with a system variant of disease, can lead to development of conditions menacing to a life.

The table № 3.2.3. Dynamics of indicators of activity of disease against treatment etanertseptom at children with system variant JUIA.

** р=0,001, * r