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.
NSAIDs are not recommended during pregnancy, particularly during the third trimester . While NSAIDs as a class are not direct teratogens , they may cause premature closure of the fetal ductus arteriosus and kidney ADRs in the fetus. Additionally, they are linked with premature birth  and miscarriage .   Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies .  Additionally, indomethacin is used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal kidney blood flow.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, which comprise an important compensatory mechanism for maintaining renal blood flow, glomerular filtration, and water and electrolyte homeostasis in the setting of a number of pathophysiologic states including CKD. CKD patients are, therefore, at risk for adverse renal side-effects of NSAIDs, including acutely worsened renal function, hyperkalemia, hyponatremia, sodium retention, and exacerbation of hypertension. Although these effects are generally reversible upon discontinuation of the drugs, CKD patients must be monitored closely while taking NSAIDs.