Background The introduction of biological therapy drugs contributes to changing the natural course of the disease in cases of severe JIA.
Objectives To clarify impact of tocilizumab on the course of JIA.
Methods Of 117 children with JIA being under observation for the last five years 35% receive biologic therapy (3 etanercept, 21 adalimumab, 11 tocilizumab) during 1–5 years. Retrospective analysis of the data from clinical, laboratory and instrumental studies in the dynamics of the TCZ treatment of patients with JIA was made.
Results Among children treated with TCZ 63,6% were sJIA cases, 63,6% were female. Age of onset 6,1±4,7y (6m–10,5y), all had acute onset, hyperthermia, severe pain syndrome, exudative arthritis in all pJIA cases and half of sJIA cases. ESR 39,7±11,2 mm/h, CRP 53,8±16,1 mg/L, all patients had anemia, leukocytosis and were seronegative for RF and anti-CCP, 3 of pJIA patients revealed ANA (1:1200–2400), IL-6 19,78±6,7 pg/ml. Before biological therapy has begun, SJIA courses were continuously relapsing in all cases with 4,7±2,1 exacerbations per y; during the 1st y of illness 8 cases run with coxitis, 7-cervical spine involvement, 9-wrists damage. All patients received CS therapy before initiating TCZ, 45,4% of them with pulse therapy, all marked by the inability to minimize the CS dose, all received 2–4 DMARDs in high doses. 2 patients received adalimumab before TCZ treatment. Elapsed time from the onset to biological agent prescription was 5,37±5,1 years. At the start of biological therapy JADAS was 19,6±5,7, stunted growth -1,88±0,3 σ, according to densitometry, osteoporosis took place in every case (Z=-2,7±1,1). After 6 month JADAS was 1,8±1,1, ESR and CRP normalized, IL-6 rate remained high in 36% cases. After 1 year the severity of osteoporosis decreased (Z = -1,17±0,8), bone deficiency depended on duration of TCZ exposure (r = -0,72) and on the elapsed time from onset of JIA before the start of biological therapy (r = -0,84). The mean increase in height was 7.73 cm/patient-year (+1±0,8 σ). Stunted growth depended on the duration of the TCZ course (r=-0,81) and the elapsed time from the onset of the disease to the start of biological therapy (r=-0,72). After 1 y of TCZ all children had normal weight and BMI for age (19,89±1,9). After 1–5 ys of treatment JADI was evaluated 2,1±2,9 (0–7), the degree of joint damage didn't depend on the duration of the biological therapy (r=0,24) and correlated with the time elapsed from the onset of the disease before treatment (r =0,59). During the treatment, exacerbations were marked only in 1 case, adverse events in 3 cases (skin infections, leukopenia). TCZ therapy allowed to completely discontinue CS in 63,6% cases, minimize them to 4 mg/day in others, DMARDs are discontinued in 9% cases.
Conclusions Administration of TCZ is rather effective towards the drug induced remission even in long-time JIA process, but the least joint damage, osteoporosis and stunted growth can be obtained with earlier tocilizumab prescription. Reclassification of patients according to specific clinical and immunological features leads to optimization of the selection of targeted therapy.
While identifying in onset of JIA polyarticular destruction and systemic features (hyperthermia, anemia, leukocytosis, high laboratory activity and severity of osteoporosis) one should consider the feasibility of early administration of tocilizumab.
Disclosure of Interest None declared