Background: In rheumatoid arthritis (RA), therapy with disease modifying antirheumatic drugs (DMARDs) frequently needs to be changed due to insufficient effectiveness. We aimed to compare the clinical outcomes of two potential strategies for patients experiencing DMARD discontinuations related to ineffectiveness: switching to another DMARD or step-up combination therapy of the present DMARD with a new one.
Methods: In a large observational database of 4585 DMARD courses in 1214 patients with RA, we identified all patients who had experienced a change in treatment regimen, and compared retention, effectiveness, and safety, of these subsequent treatment courses between the two strategies (switching vs. step- up combination). All analyses were stratified according to the type of the new DMARD into methotrexate (MTX), sulfasalazine (SSZ) or leflunomide (LEF); all other DMARDs were excluded.
Results: Kaplan-Meier analysis for MTX courses showed no significant difference in overall retention rates between the strategies of adding MTX and switching to MTX (p=0.49 by log-rank test). Likewise, switching or adding did not result in significantly different retention rates for SSZ and LEF (p=0.61 and p=0.74, respectively). This similarity between strategies remained after adjusting for several confounding variables. The frequencies of treatment terminations related to ineffectiveness or toxicity were likewise similar between the two strategies for the MTX, SSZ, and LEF groups. This was also confirmed by the similarity of erythrocyte sedimentation rate levels that were reached at the end of the two therapeutic strategies for all three drugs, in adjusted analysis.
Conclusion: Given all limitations of observational studies, the present data indicate that in situations of ineffective DMARD therapies, step-up combination therapy using traditional DMARDs, such as methotrexate, sulfasalazine, or leflunomide, bears no clear clinical advantage over switching to the new DMARD. Our results do not implicate any predication about step up design including biologicals, where the benefit of combination therapy has been suggested convincingly.
- combination therapy
- rheumatoid arthritis
- therapeutic strategy