Oral vs. subcutaneous (sq) administration of methotrexate is generally considered equivalent in rheumatoid arthritis (RA) treatment. However, the enhanced bioavailability of sq methotrexate may make this route of administration preferable to the oral route in certain patients.
Safety data obtained from randomized clinical trials designed to evaluate the efficacy of rheumatoid arthritis (RA) drugs can be misleading for several reasons. Often, the studies are short term (6 months or less), and are highly selective of the subjects included (usually subjects with very active disease and with few medical comorbidities). In addition, background DMARDs are usually restricted to methotrexate.
The molecular mechanisms leading to erosive joint damage in some, but not all, patients with rheumatoid arthritis (RA) are incompletely understood. Downstream effects of inflammatory cytokines produced by rheumatoid synovium include the induction of RANKL, a powerful osteoclast activator, the action of which is physiologically opposed by its naturally occurring antagonist osteoprotegerin (OPG).
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Hematologic malignancies, particularly lymphomas, are more prevalent in RA patients. Case reports have suggested an association between RA therapeutics and the development of lymphoma, although it has been problematic using conventional epidemiologic methods to disassociate the potential for the RA disease process, presumably mediated through chronic systemic inflammation, to contribute to this risk. These concerns have limited the use of RA therapies in some patients.
