Methotrexate is the recommended first-line DMARD in RA based on its effectiveness, fairly good safety profile, and moderate cost [7], [46], [47], [48], [49] and [50]. The recommended starting dosage is

10–15 mg/week orally followed by rapid dose escalation (e.g., 5-mg increments every 1–4 weeks) to achieve the optimal dosage of about 0.3 mg/Kg/week, i.e., 15–25 mg/week in most patients, depending on effectiveness and safety, as well as on the specific characteristics of each patient. check details In the event of an inadequate treatment response or failure to tolerate methotrexate, subcutaneous administration of the drug can be considered. Finally, supplementation with at least 5 mg/week of folic acid at a distance from the methotrexate dose is recommended [51]. Methotrexate

is thus the first-line drug in patients with active RA. A major BMN 673 manufacturer issue is whether methotrexate should be used alone or combined with other synthetic DMARDs. A Cochrane Collaboration meta-analysis published in 2010 found no improvement in the risk/benefit ratio with drug combinations compared to methotrexate alone [52]. Two recent studies compared the clinical and structural efficacy of the triple drug combination methotrexate + sulfasalazine + hydroxychloroquine to methotrexate alone [53] and [54]. One of these studies, tREACH, was a randomized controlled single-blind trial in patients with recent-onset RA at high risk

for progression to established RA but without specific criteria of adverse prognostic significance [53]. Glucocorticoid therapy was given also. Some of the study parameters showed greater improvements with the triple drug http://www.selleck.co.jp/products/Gefitinib.html combination. The other study, TEAR, involved tight disease control with dynamic treatment adjustments to achieve a predefined target and found no differences in clinical or radiographic outcomes between triple therapy and methotrexate alone [54]. The CareRA study done in Belgium provided new information in late 2013 [55]. This randomized controlled trial found no evidence that triple DMARD therapy was better than methotrexate alone (with glucocorticoid therapy in both treatment arms) [55]. Finally, patient acceptance of triple therapy is sometimes poor (e.g., due to the large number of tablets and adverse events), a fact that translates into low treatment continuation rates [56]. Thus, given the inadequate amount of consistent data, methotrexate alone is recommended for the first-line treatment of active RA. In patients with contraindications or intolerance to methotrexate, leflunomide and sulfasalazine have been proven effective in alleviating the symptoms and decreasing the structural damage [57].