Assessment of antirheumatic activity in man

Abstract

Although so-called disease-modifying antirheumatic drugs (DMARDs) have been trialled in a number of chronic arthropathies, including psoriatic arthritis, Reiter's syndrome and ankylosing spondylitis, it is their application in the treatment of rheumatoid arthritis (RA) that has attracted the greatest attention. The drugs of interest are slower in their onset of action than the non-steroidal anti-inflammatory drugs (NSAIDs) and appear to differ in the dimensionality of the response induced, producing less dramatic effects on pain and swelling but possibly having long-term advantage with respect to physical function and radiographic progression of disease. There has been much debate as to the correct terminology for this class of drugs, which in Canada includes the antimalarials, chloroquine and hydroxychloroquine, as well as sulphasalazine, sodium aurothiomalate, auranofin, D-penicillamine, methotrexate, azathioprine and cyclophosphamide. Other drugs in this group that have been tested but are not in routine use include levamisole and cyclosporin A. Some authors have favoured the term remission-inducing drugs (RIDS) or slow-acting remission-inducing drugs (SARIS), although others contend that, since a complete remission is rarely achieved, DMARDs is a better eponym. However, it is clear that compared to a placebo or no treatment, even NSAIDs modify the disease process. While it may be suggested that such a response leaves the long-term consequences of disease unaltered, it is hard to accept that the long-term outcome of RA is not improved in some way for those patients who demonstrate a substantial and sustained response in pain, swelling, stiffness, range of movement and activities of daily living to either a single trial or serial trials of several NSAIDs prescribed over time. Given the aforementioned problems, the term 'slow-acting antirheumatic drugs' or SAARDs is to be preferred (Currey, 1984). The majority of SAARDs appear at least in vitro to modulate the immune response, although some have received the specific designation of immunosuppressive or cytotoxic agents. It is because NSAIDs modify the symptoms of disease and SAARDs differ in their induction-response interval and may affect aspects of disease relatively untouched by NSAIDs that clinical trials of SAARDs differ in certain respects from those of NSAIDs. Furthermore, until recently, drugs such as methotrexate, azathioprine and cyclophosphamide were regarded as drugs