AB0980 EFFICACY OF ETANERCEPT TREATMENT FOR CHILDREN WITH KAWASAKI DISEASE INTRACTABLE TO INTRAVENOUS IMMUNOGLOBULIN THERAPY IN RUSSIAN CHILDREN
Authors: Anastasiya Glazyrina, Seda Kurbanova, Marina Kantemirova, Yuliya Novikova, Dmitry Ovsyannikov, Elena Zholobova, Saniya Valieva, Elena Petryaykina
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Kawasaki disease (KD) is recognized in developed countries as a fundamental reason of acquired heart diseases in children nowadays. The main treatment is infusion of intravenous immunoglobulin (IVIG) at a dose of 2 g/kg. However for about 10-30% of children is reported the development of resistance to standard therapy: continuance of fever (≥38,0 °C) or recurrency of fever after 36 hours afebrile period (T&lt;37,5 °C), but not later than on the 7th day after completion of the IVIG infusion at a dose of 2 g/kg. Until now there are no unified recommendations for treatment of such patients. As alternative therapy researchers empirically apply second infusion of IVIG (77%), high doses of glucocorticoids (18%), blockers of tumor necrosis factor α (3%) and interleukin-1, cyclosporine and other cytostatic drugs. <h3>Objectives</h3> Efficacy evaluation of therapy by inhibitor of TNF-alpha (Etanercept) in treatment of KD immunoglobulin -resistant forms according to the data from Morozovskaya Children's City Clinical Hospital,Moscow. <h3>Methods</h3> There were examined 152 patients (boys:girls – 2:1, median age Me = 21 months [10;36]) with KD hospitalized in Morozovskaya Children's City Clinical Hospital in 2014-2018. The frequency of complete form of KD was 80,6%. All children had a standard therapy –IVIG. Efficacy evaluation was based on normalization of body temperature, decrease of neutrocytosis, decrease of C-reactive protein (CRP) level. In case of ineffectiveness of therapy the second infusion of IVIG, pulse-therapy and inhibitor of TNF-alpha (Etanercept) were used <h3>Results</h3> The resistance to standard IVIG therapy was revealed in 16 children (10,5%), mostly in boys (4,3:1) at the age of Me = 21,5 months [9,5; 34]. Complete form of KD was diagnosed in 11 patients (68,8%), incomplete form - in 5 children (31,2%). Cardiovascular lesions were noted in 14 children (87,5%): pericarditis - in 2 (12,2%), coronary arteries (CA) lesions – in 12 (75%), with formation of aneurysms in 8 (50%), including the giant ones in 3 children (18,8%); peripheral arteries damages were noted in 2 children (12,5%), thrombosis and thromboembolism – in 4 children (25%). To all of children was made the second IVIG infusion, 13 of those children (81,2%) had a positive effect:11 children with complete form of KD, 2 children with incomplete form of KD. For 3 children (18,7%) with incomplete form of KD and significant cardiovascular changes (pericarditis, giant aneurysm of coronary and peripheral arteries,thrombosis and thromboembolism) it was needed an additional therapy. As a second-line therapy the methylprednisolone pulse-therapy was used in 2 children(12,5%) at a dose of 10 mg/kg, without sufficient effect. For these three patients(3) as a third-line therapy was applied Etanercept at a dose of 0,8 mg/kg/a week subcutaneousely. In all children normalization of body temperature, decrease of leukocytosis by factor of 1,5-3 and decrease of CRP by factor of 10-15 occurred after three injections of Etanercept. However, for 1 child it was needed the additional fourth injection of Etanercept because of repeated fever, increased laboratory parameters, development of thrombosis of the left coronary artery after 2 weeks upon discharge. <h3>Conclusion</h3> The frequency of immunoglobulin-resistant forms was 10, 5%. The first-line therapy of resistance (second IVIG-infusion) was efficient in 13 children (81,2%). Methylprednisolone pulse therapy was ineffective. The use of 3 subcutaneous injections of Etanercept at a dose of 0,8 mg/kg/ a week resulted in decrease of intensity of inflammatory changes and in fever relief, but it did not prevent the development of relapse and thrombosis of coronary arteries. <h3>Disclosure of Interests: </h3> Anastasiya Glazyrina: None declared, Seda Kurbanova: None declared, Marina Kantemirova: None declared, Yuliya Novikova: None declared, Dmitry Ovsyannikov: None declared, Elena Zholobova Grant/research support from: Roche, Pfizer, Novartis, Consultant for: Pfizer, AbbVie, Roche, BMS, Novartis, MSD, Speakers bureau: Pfizer, AbbVie, Roche, BMS, Novartis, MSD, Saniya Valieva: None declared, Elena Petryaykina: None declared