Anakinra in treatment of pediatric inflammatory multisystem syndrome temporally associated with SARS-COV2 infection (PIMS-TS) with cardiac involvement

ABSTRACT

Background and Aim: PIMS-TS often affects the cardiovascular sys-tem resulting in myocarditis and coronary artery abnormalities (CAA). Immunosuppressive therapy is the primary treatment of PIMS-TS;however, controversies on the best regimen remain. The use of anakinra as a second-line treatment in children with cardiac involvement is often proposed lately. This prospective observational study aimed to determine the incidence of cardiac involvement in PIMS-TS and to evaluate the effectiveness and safety of anakinra in its treatment Methods: From July 2020 till December 2021, we have treated 22 children with PIMS-TS (12 boys, 10 girls;aged 0,3-15,75y (median-4y). Echocardiography assessing coronary arteries and systolic function was performed at admission, during the hospitalization, at discharge and 6-8 weeks after the onset. Result(s) Fourteen(63%) of the patients had coronary artery dilata-tion (z-score 2,1-11,8;median2,9), 6(27%) deterioration of sys-tolic function, 5(22%) both, 20(90%) had elevated NTproBNP. Only in 2 children (9%) there was no cardiac involvement;in 3(14%) the only cardiac sign was elevated NTproBNP. Two children required admission to ICU. In the first line immuno-suppressive treatment, we administered intravenous immunoglo-bulins (IVIG) in dose 2g/kg in all patients-of which in 16 as a monotherapy, in 6 together with glucocorticosteroids (GCS) because of their severe condition. Seven patients (32%) recovered after a single IVIG infusion, 3(14%) after repeated IVIG infusions. In this subgroup all CAA normalized or got significantly smaller with the change in the median z-score from 2,8 to 1,3. In 10 (45%) patients with cardiac involvment and insufficient response (4 with previous IVIG treatment, 6 with previous IVIG+GCS treatment) we administered anakinra obtaining clinical, laboratory and echo-cardiographic improvement in all of the patients (good systolic function and normalized or significantly smaller CAA from z-score median = 2,8 (range 2,1-11,8) to z-score median = 1,9 (range0-3,2)), with no side effects. The median time to introduce anakinra (for median 9 days treatment) was 4 days after the first-line treatment. In 2 patients with suboptimal effect of first-line IVIG monotherapy, but no cardiac involvement, GCS as the second-line treatment were used. Median time of hospitalization was 18 days Conclusion(s) Cardiac involvement is common in PIMS-TS. Anakinra seems to be effective and safe in its treatment.