Sulphasalazine and related drugs in rheumatoid arthritis

Abstract

The standard approach to the drug therapy of rheumatoid arthritis involves the initial use of simple analgesics and non-steroidal antiinflammatory drugs. If this treatment fails to produce adequate symptomatic improvement in the presence of active inflammatory disease patients then progress to the so-called second line drugs (also called slow acting antirheumatic drugs, disease modifying antirheumatic drugs or d-penicillamine like drugs). These drugs produce improvement in both symptoms and routine laboratory measures of inflammation such as the erythrocyte sedimentation rate and C-reactive protein. However, controversy remains as to whether they retard disease progression (Iannuzzi et al., 1983)., Their onset of action is slow with a long lag phase (between 6 weeks and 6 months) before any benefit is seen. Because of their propensity to cause serious side-effects close monitoring of patients taking these drugs is necessary. Seventy percent of rheumatoid patients attending a hospital clinic require second line drugs at some time (Pullar and Wright, 1987). The drop-out rate from treatment because of inefficacy or toxicity with second line drugs is high with between 61% and 92% of patients terminating treatment within four to five years (Pullar et al., 1985a; Situnayake et al., 1987). However, four years after starting second line therapy 69% of patients attending a clinic still require second line drugs (Pullar et al., 1985a). Until recently the only second line drugs used in routine clinical practice were injectable gold salts (sodium aurothiomalate or sodium aurothioglucose), d-penicillamine and the antimalarials (chloroquine or hydroxychloroquine). It is apparent, therefore, that the potential exists to rapidly exhaust the supply of available second line drugs thus necessitating use of more toxic drugs such as cytotoxic agents or systemic corticosteroids. There is, therefore, a need for more, preferably less toxic and/or more effective, second line drugs. Several drugs such as levamisole, dapsone, captopril and sulphasalazine have been found over the past few years to have second line properties and of these sulphasalazine has the most favourable toxicity profile and has found its way into routine clinical practice.