Methotrexate: Optimizing the Efficacy in Rheumatoid Arthritis

Abstract

Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA). The drug had been synthesized in 1948 and first tests to treat patients with psoriasis and RA were published in 1951. However, until the 1980s there was only limited use of MTX in the treatment of RA. Since the 1990s MTX is the disease-modifying antirheumatic drug (DMARD) of first choice for the treatment of RA in most countries worldwide. By definition, DMARDs in RA are those compounds for which an inhibiting effect on radiographic progression has been demonstrated. Several combinations of DMARDs have been tested, most commonly with MTX as the anchor drug. Regarding the route of administration of MTX there is some evidence that the parenteral route, most often performed subcutaneously, has some additional benefits over the oral route. In MTX monotherapy, dosages up to 30 mg/ week are now used. There are now three main combinations that are playing an important role: MTX þ sulfasalazine (SSZ) þ hydroxychloroquine, MTX þ leflunomide (LEF), and MTX þ biologics such as antitumour necrosis factor (anti-TNF) and other new compounds which block the interleukin 6 (IL6) receptor or T-cell activation and delete B cells. Regarding clinical efficacy, MTX monotherapy has performed almost similarly well in comparison with biologic monotherapy, both usually combined with glucocorticoids. However, structural damage is usually inhibited to a significantly greater degree with the biologics. The combination of MTX with biologics has proven superior to either agent alone in all aspects. Current strategic regimens which concentrate on systematic ways to bring patients into remission all include MTX as first choice.

Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheumatoid Arthritis Patients

“…However, the average dose of MTX was not decreased during the study period of 24 weeks. This might have been because MTX is recognized as a 'first-line treatment' and 'anchor drug' for RA worldwide and there is abundant evidence about its efficacy available [30]. However, adverse effects were reported in 27% of RA patients receiving low-dose MTX (10 mg/week for at least 3 months), especially hepatic and hematological toxicities [31], and several studies have suggested that tapering or discontinuing MTX does not reduce the efficacy of combination therapy for RA [32,33].…”

Protective Effects of Methotrexate against Proatherosclerotic Cytokines: A Review of the Evidence

“…Methotrexate, an analogue of the B vitamin folic acid, is a first-line synthetic DMARD for the management of RA and other autoimmune diseases that is normally administered once a week, either orally, subcutaneously, or intramuscularly, with doses ranging between 5 and 25 mg [ 67 , 68 ]. Notably, methotrexate is the only DMARD that has demonstrated significant survival benefits in patients with RA [ 69 – 71 ].…”

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study

“…SC MTX dose was maintained or reduced whenever other DMARDs were added to the treatment. The combination of other DMARDs with SC MTX is more effective than the monotherapy with these agents [ 12 – 17 ]. Although the efficacy of SC MTX was not evaluated in the UMAR study, published evidence reveals the superiority of SC over oral MTX [ 3 , 17 ].…”