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Recent advances in knowledge of the pathogenesis of rheumatoid arthritis (RA) has led to promoting very early intervention.To assess the efficacy of therapeutic interventions in preventing or delaying RA onset with a systematic literature review (SLR) and meta-analysis (MA).The SLR aimed to include all reports of randomised controlled trials of disease-modifying antirheumatic drugs or glucocorticoids used in patients presenting genetic and/or environmental risk factors for RA and/or systemic autoimmunity associated with RA, and/or symptoms without clinical arthritis and/or unclassified arthritis and in patients with RA. We searched PubMed, EMBASE and Cochrane databases for English articles published from 2006 to 2016 using the keywords ‘undifferentiated arthritis’ or ‘very early rheumatoid arthritis’ with ‘therapy’ or ‘treatment’. Main outcome was RA occurrence, defined as fulfilment of the 1987 ACR criteria. The MA was performed with RevMan with the Mantel-Haenszel method.Among 595 abstracts screened, 10 reports of trials were selected. The studies included 1156 patients, with mean symptom duration 16.2±12.6 weeks. The occurrence of RA was available for nine studies, assessing methylprednisolone, methotrexate, a tumour necrosis factor blocker, abatacept or rituximab. In the group arthralgia without arthritis (people at risk of RA), the MA of the two available studies did not show significant reduction in RA occurrence at week 52 or more (pooled OR 0.74, 95% CI 0.37 to 1.49). For people with undifferentiated arthritis, the MA of the seven available studies revealed significant risk reduction with OR 0.73(95% CI 0.56 to 0.97).This MA demonstrates that early therapeutic intervention may significantly reduce the risk of RA onset in this very first phase of the disease.