IntroductionRheumatoid arthritis is a common debilitating autoimmune disease affecting men and women of different ages worldwide. Methotrexate is a well-known initial treatment for rheumatoid arthritis, but is it enough? New studies show that a class of drugs called TNF inhibitors decrease disease progression when used alongside methotrexate in the early treatment of rheumatoid arthritis. Of the available TNF inhibitors, Enbrel and Humira are the most commonly used because they have the same mechanism of action and only require a once-weekly injection, leading to better compliance. Due to their identical mechanism of action, Enbrel and Humira can be used interchangeably and therefore both will be discussed in this review. One of the biggest challenges with using TNF inhibitors in the treatment of rheumatoid arthritis is knowing when to introduce them. in addition to methotrexate. Should patients receive these TNF blockers early in the disease or once methotrexate monotherapy fails to decrease disease activity? This is a question frequently asked by patients and doctors. The goal of using these drugs together is to reduce disease activity to low activity with the possibility of induction of remission. The following paragraphs will review the most recent studies and provide the information needed to understand how best to combine these medications when treating patients with rheumatoid arthritis. Summary of Literature Review Studies in this review were found using the medical school's PubMed database. Saint Louis University Library. The search criteria were limited to human studies carried out within the last 5 years in the English language, with an emphasis on randomized control... middle of article...... e. This study was found to have many strengths and weaknesses. . The main strength of the study was that it was double-blind, multicenter and placebo-controlled1. Other strengths include having the same doctor follow the same patients at each encounter to record the number of tender and swollen joints found; Patients were not allowed to use NSAIDs and analysis of results was intention-to-treat, so as long as patients received an injection of Humira or placebo, they were included in the results. Weaknesses included the fact that the study never mentioned how the two groups were randomized in the study; acetaminophen was allowed to be taken freely by patients; the authors of the study were reimbursed; and triple therapy with sulfasalazine and hydroxychloroquine plus methotrexate were introduced in eighteen patients on Humira compared to twenty-seven patients on placebo.1.