Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial. On behalf of the Rheumatic Research Foundation Utrecht, The Netherlands

Abstract

Objectives: To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect.

Methods: Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a "mild SAARD with a long lag time" (hydroxychloroquine, if necessary replaced by auranofin); (II) a "potent SAARD with a long lag time" (intramuscular gold, if necessary replaced by D-penicillamine); (III) a "potent SAARD with a short lag time" (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up.

Results: All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10 v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies.

Conclusion: Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or D-penicillamine) was associated with increased toxicity.

Figure 1

Mean disability score in 150 patients with available data on disability for all nine measurements in each therapeutic strategy. There was a significant difference between strategies I and III (p = 0.04), and a significant decrease in disability over time in each strategy (analysis of variance for repeated measurements).

Figure 2

Mean pain score in 243 patients with available data on pain for all nine measurements in each therapeutic strategy. Significant decrease in pain score over time in each strategy, no significant difference between the strategies (p = 0.23) (analysis of variance for repeated measurements).

Figure 3

Mean joint score in 247 patients with available data on joint score for all nine measurements in each therapeutic strategy. Significant decrease in joint score over time in each strategy, no significant difference between the strategies (p = 0.30) (analysis of variance for repeated measurements).

Figure 4

Mean ESR score in 237 patients with available data on ESR for all nine measurements, in each therapeutic strategy. Significant difference between strategies I and II (p = 0.01), and significant decrease in ESR over time in each strategy (analysis of variance for repeated measurements).

Figure 5

Radiological progression in the three strategies. Significant increase over time in each strategy with significant interaction between overall time-treatment effect and strategy effect, showing a faster increase in strategy I than in strategy II (p = 0.03) and strategy III (p = 0.01). No significant difference between the three strategies (p = 0.23) (analysis of variance for repeated measurements).

Figure 6

Percentage of patients in remission at each measurement in time. Remission is defined as morning stiffness ≤15 min, pain score ≤10 mm, joint score ≤10, and ESR ≤30 mm/ 1st h.