We identified 32 studies (1443 children) of which one study is still ongoing. In the 31 studies with data , risk of bias assessment indicated that 11 (37%) and 16 (53%) studies were at low risk of bias for sequence generation and allocation concealment respectively. Six (29%) studies were at low risk of performance and detection bias . Twenty seven (87%) and 19 (60%) studies were at low risk of incomplete and selective reporting respectively. Alkylating agents (cyclophosphamide and chlorambucil) significantly reduced the risk of relapse at six to 12 months ( RR , 95% CI to ) and 12 to 24 months ( RR , 95% CI to ) compared with prednisone alone. There was no significant difference in relapse risk at two years between chlorambucil and cyclophosphamide ( RR , 95% CI to ). There was no significant difference at one year between intravenous and oral cyclophosphamide ( RR , 95% CI to ). Cyclosporin was as effective as cyclophosphamide ( RR , 95% CI to ) and chlorambucil ( RR , 95% CI to ) at the end of therapy while levamisole ( RR , 95% CI to ) was more effective than steroids alone. However the effects of cyclosporin and levamisole were not sustained once treatment was stopped. In one small study cyclosporin significantly reduced the relapse rate compared with mycophenolate mofetil ( MD , 95% CI to ). Limited data from a cross-over study suggested that cyclosporin was more effective than mycophenolate mofetil in maintaining remission. In steroid- and cyclosporin-dependent disease, rituximab significantly reduced the risk of relapse at three months compared with conventional therapy . Mizoribine and azathioprine were no more effective than placebo or prednisone alone in maintaining remission.
Addiction to cortisone was the subject of the 1956 motion picture, Bigger Than Life , produced by and starring James Mason . Though it was a box-office flop upon its initial release,  many modern critics hail it as a masterpiece and brilliant indictment of contemporary attitudes towards mental illness and addiction.  In 1963, Jean-Luc Godard named it one of the ten best American sound films ever made.  John F. Kennedy needed to regularly use corticosteroids such as cortisone as a treatment for Addison's Disease .