CAN DRUGS ALTER THE OUTCOME OF RHEUMATOID ARTHRITIS?

It is difficult to judge the efficacy of drug treatment of rheumatoid arthritis (RA) because of the problems of assessing progress of the disease. Radiological assessment is probably the best way to detect unequivocal progression of RA, but it is not always straightforward. I f drug "treatment is to affect the course of RA, it should not only slow or stop radiological damage but also reduce the laboratory indices of active disease. The only laboratory tests that have been correlated with radiological progression are the erythrocyte sedimentation rate and measurement of C.-reactive protein and possibly rheumatoid factor . ESR and acute­phase reactants are easy to measure and indicate which drugs might be expected to affect outcOme. Non -steroidal anti -inflammatory drugs do not change the outcome of RA. In fact , relief of pain may make the disease worse. Most of these drugs relieve symptoms by inhibiting prostaglandin synthesis, but this action possibly exacerbates joint destruction. Gold, penicillamine and chloroquine can all reduce ESR and concentrations of acute-phase proteins. The relief of symptoms is slow to start (8-12 weeks), but when they are beneficial they are usually far more so than non-steroidal anti-inflammatory drugs. All 3 drugs can lower immunoglobulin levels and reduce Rose-Waaler titer. There is even some direct evidence of reduction in the progress of bony damage with gold, and it has been suggested that the earlier treatment starts, the better the results. Most measures of rheumatoid disease improve with penicillamine, but there is so far no direct evidence that it arrests erosive damage. Penicillamine has the potential capability of restoring serum histidine levels to near normal-. Chloroquine is symptomatically effective, and lowers ESR and rheumatoid factor titer, but it does not seem to delay radiological progression. Levamisole and dapsone are recent additions to antirheumatic treatment and su(fasalazine has been recently reintroduced for this indication in Britain. Levamisole is clinically effective and lowers ESR, but is too toxic for routine use. Dapsone and sulfasalazine improve some patients' symptoms over several weeks and reduce ESR and acute-phase proteins. Sulfasalazine has given particularly encouraging results. Corticosteroids have rapidly improved symptoms and lowered ESR in most trials, but by the end of a year results differ little from those with aspirin, except that corticosteroids, unlike aspirin, can halt aggressive or rapidly advancing disease. However, the doses needed are too high for long term treatment. Local injections of steroids can also have adverse effects. There is no strong evidence that conventional doses of corticosteroids are regularly able to change the course of RA. Cyclophosphamide and azathioprine (cytotoxic drugs) are not widely used, despite reported improvement in clinical signs of disease activity, because of their high general toxicity. Conclusions: Although some drugs appear to be altering the natural hi~tory of RA in some patients .. no drug is effective for all patients. Even where there is a good response, relapse may occur despite continued treatment. However, most rheumatologists have seen patients with established active RA who achieved long lasting remissions qn a particUlllr drug. One priority for the future should be identification of the characteristics of patients who respond to each drug . Another may be to compare clinical and biochemical variables to decide whether drugs have a long term effect.

Vv'ith careful radiological assessment over a long period (e few months is inadequ­ate) we should be able to give a definitive answer to the vexed qu~stion of whether drug treatment can alter the outcome of rheumatoid arthritis.

Wright. V. and Amos. R.: British Medical Journal 280: 964 (5 Apr 1980)

4 INPHARMA 12 Jul 1980 0156-2703/80/ 0712-0004 $00.50/0 © AOIS Press