Use of Different Immunomodulator Therapy in Children with Myocarditis- a Network Meta-analysis

Background: Myocarditis is defined as inflammation of the heart muscle, also known as inflammatory cardiomyopathy. In children, myocarditis is most likely due to viral infections. The most common viruses causing myocarditis in children are: Parvovirus, Influenza virus, Adenovirus and coxsackie virus. Immunomodulator therapy for treatment of myocarditis remains controversial. A number of controlled trials demonstrated that immunomodulator treatment might improve the function in heart failure. Hence, this network meta-analysis was conducted to see the role of different immunomodulators in children with myocarditis.

Methods: A total of 14 RCTs having 879 patients out of which 416 patients received immunomodulator therapy and 463 patients were given conservative treatment following PRISMA guidelines till August 2020 were matched for inclusion and exclusion criteria. The following search strings and MESH terms were used: "immunomodulator therapy", "pediatric myocarditis". Following this, role of different treatment options such as corticosteroids, intravenous immunoglobulin and corticosteroids plus azathioprine or cyclosporine combination on the outcome of rate of death or transplantation was analyzed. RevMan 5.3 was used for appropriate statistical tests. Fixed and Random Effect Model Test were used and p<0.05 was considered statistically significant.

Results: The adverse outcome of our study was death or need for transplantation.When all of the above mentioned drugs were compared indirectly, corticosteriods had statistically significant increased incidence of adverse outcome as compared to immunoglobulin (RR=2.045, CI=1.558 to 2.683, p<0.001 in fixed effect model). Even the combination of corticosteriods and azathioprine or cyclosporine had statistically significant increased incidence of adverse outcome as compared to immunoglobulin. (RR=1.888, CI=1.437 to 2.479, p<0.001 in fixed effect model).When the combination of corticosteriods and azathioprine when compared to corticosteriods single therapy, non-significant difference was found (RR=1.094, CI= 0.882 to 1.358, p=0.414 in fixed effect model).The overall rate of death or need for transplantation in Immunoglobulin was 12.66%, for corticosteriod alone it was 27% and for the combination it was 24.2%.

Conclusion: The present network metanalysis does not support corticosteroids or combination of corticosteroids plus azathioprine or cyclosporine as superior to intravenous immunoglobulin therapy in children with myocarditis Hence, we came to a conclusion that intravenous immunoglobulin might be beneficial in reducing death or need for transplantation in children with myocarditis.