Usefulness of three-drug additional combination therapy with bucillamine, sulfasalazine and methotrexate for refractory rheumatoid arthritis

To determine the efficacy of three-drug additional combination therapy for refractory rheumatoid arthritis (RA), we enrolled patients who had not had a satisfactory response to stepwise therapy with disease-modifying antirheumatic drugs (i.e. auranofin, gold sodium thiomalate, D-penicillamine, bucillamine or sulfasalazine) or to two-drug additional combination therapy with bucillamine or sulfasalazine plus methotrexate, or bucillamine plus. sulfasalazine. In total, 39 patients were treated and 30 patients who were treated continuously for at least 1 year were clinically evaluated. All but one patient had late-stage RA (Steinbrocker stage III or worse) and had been treated with disease-modifying antirheumatic drugs for 4-18 years (mean: 9 years). Despite the low doses used, disease activity significantly improved in all patients: the Lansbury activity index decreased from 55.2% at baseline to 30.6% at 3 months and this significant improvement was maintained for 3 years. Significant decreases in inflammatory parameters, such as erythrocyte sedimentation rate and C-reactive protein, as well as improvement in relevant immunological parameters were also recorded in many of the patients. Adverse drug reactions occurred in 13 patients (33%.), but five continued the treatment at a reduced dose. Our findings suggest that three-drug additional combination therapy will be very useful for refractory RA.