Nineteen RCTs (820 children enrolled; 773 evaluated) were included. Most studies were small. Eleven studies were at low risk of bias for allocation concealment and only four studies were at low risk of performance bias . Fifteen, eight and 10 studies were at low risk of detection bias , attrition bias and reporting bias respectively. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission. However this was based on only eight children who achieved remission with cyclosporin compared with no children who achieved remission with placebo /no treatment in three small studies (49 children: RR , 95% CI to ). Calcineurin inhibitors significantly increased the number with complete or partial remission compared with IV cyclophosphamide (2 studies, 156 children: RR , 95% CI to ; I 2 = 20%). There was no significant differences in the number who achieved complete remission between tacrolimus versus cyclosporin (1 study , 41 children: RR , 95% CI to ), cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study , 138 children: RR , 95% CI to ), oral cyclophosphamide with prednisone versus prednisone alone (2 studies, 91 children: RR , 95% CI to ), IV versus oral cyclophosphamide (1 study , 11 children: RR , 95% CI to ), IV cyclophosphamide versus oral cyclophosphamide plus IV dexamethasone (1 study , 49 children: RR , 95% CI to ), and azathioprine with prednisone versus prednisone alone (1 study , 31 children: RR , 95% CI to ). One study found no significant differences between three agents (cyclophosphamide, mycophenolate mofetil, leflunomide) used in combination with tacrolimus and prednisone. One study found no significant difference in the percentage reduction in proteinuria (31 children: -12; 95% CI -73 to 110) between rituximab with cyclosporin/prednisolone and cyclosporin/prednisolone alone. Two studies reported ACEi significantly reduced proteinuria.
Methotrexate is now considered the first-line DMARD agent for most patients with RA. It has a relatively rapid onset of action at therapeutic doses (6-8 weeks), good efficacy, favorable toxicity profile, ease of administration, and relatively low cost. When looking at groups of patients on different DMARDS, the majority of patients continue to take Methotrexate after 5 years, far more than other therapies reflecting both its efficacy and tolerability. Methotrexate is effective in reducing the signs and symptoms of RA, as well as slowing or halting radiographic damage. It was as effective as leflunomide and sulfasalazine in one study, and its effectiveness given early and in higher doses approached the efficacy of etanercept and adalimumab as single therapies in terms of signs and symptom improvement. Methotrexate is also effective in many other forms of inflammatory arthritis including psoriatic arthritis and other spondyloarthopathies, and is used in many other autoimmune diseases.
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