Prospective six year follow up of patients withdrawn from a randomised study comparing parenteral gold salt and methotrexate

Abstract

Objective: To confirm the impression of a better outcome of patients withdrawn from parenteral gold salt therapy compared with those withdrawn from methotrexate.

Methods: Patients with early, active, and erosive RA were randomised for a double blind trial to receive either weekly 15 mg intramuscular methotrexate or 50 mg goldsodiumthiomalate. If the drug had to be withdrawn because of side effects treatment was continued with the other drug in still active disease. Patients with insufficient response were treated with a combination of both drugs. All patients were followed up by an extended clinical and radiographic evaluation.

Results: 64 patients each were allocated to methotrexate and gold treatment. After 72 months a complete record was available for 88% of patients. Within the first 36 months 38 patients withdrew from gold treatment (95% because of side effects) and 23 patients withdrew from methotrexate (57% because of side effects). A significant 40% to 70% improvement of all parameters (erythrocyte sedimentation rate, C reactive protein, swollen and tender joints, radiological progression) compared with baseline was observed in patients completing their randomised treatment with gold or methotrexate. The same improvement over three years was seen in patients who withdrew from gold treatment, while patients withdrawing from methotrexate experienced a deterioration of their disease.

Conclusion: Withdrawals represent the majority of patients in long term drug trials. Patients with early RA stopping gold because of side effects show almost the same sustained improvement as patients continuing gold or methotrexate. Patients withdrawn from methotrexate experience a reactivation of their disease.

Figure 1

(A) Proportion of patients with good response according to the EULAR criteria in completers and withdrawals (GSTM and MTX). (B) Proportion of patients with moderate response according to the EULAR criteria in completers and withdrawals (GSTM and MTX).

Figure 2

Swollen joint count in completers and withdrawals (GSTM and MTX). Response to treatment shown as percentage of baseline.

Figure 3

C reactive protein in completers and withdrawals (GSTM and MTX). Response to treatment shown as percentage of baseline.

Figure 4

Slope of radiological deterioration in completers and withdrawals (GSTM and MTX). Average increase in Ratingen score per month.