Article Text
Abstract
Objective: To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy.
Methods: Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks. Inadequate responders then entered the double blind phase and received a further 24 weeks’ treatment with leflunomide (20 mg once daily) plus sulfasalazine (final dose 2 g once daily), or placebo plus sulfasalazine (dose as above). The primary efficacy variable was the DAS28 response rate, and secondary efficacy outcomes were ACR 20%, 50%, and 70% response rates. Adverse events, including standard laboratory tests, were recorded.
Results: 106 inadequate responders entered the double blind phase; 56 received leflunomide plus sulfasalazine, and 50 placebo plus sulfasalazine. In the intention to treat population, more patients receiving leflunomide plus sulfasalazine (25/56 (45%)) achieved a DAS28 response than those receiving placebo plus sulfasalazine (17/50 (34%)) (p = 0.179). In week 24 completers, more patients receiving leflunomide plus sulfasalazine (17/56 (30%)) were DAS28 responders than those receiving placebo plus sulfasalazine (10/50 (20%)) (p = 0.081). Comparable numbers in each group were ACR 20% responders; the ACR 50% response rate was significantly higher in the leflunomide plus sulfasalazine group (8.9%) than in the placebo plus sulfasalazine group (0%) (p = 0.038). The safety profiles of both groups were comparable.
Conclusion: Patient numbers are small and firm conclusions cannot be reached, but a non-significant benefit is indicated for combining leflunomide with sulfasalazine compared with switching to sulfasalazine alone in patients inadequately responding to leflunomide.
- ACR, American College of Rheumatology
- ALT, alanine aminotransferase
- DAS28, 28 joint count Disease Activity Score
- DMARD, disease modifying antirheumatic drug
- ESR, erythrocyte sedimentation rate
- ITT, intention to treat
- LOCF, last observation carried forward
- PMN, polymorphonuclear
- RA, rheumatoid arthritis
- RELIEF, Rheumatoid arthritis Evaluation of Leflunomide further Insights into its Efficacy
- RF, rheumatoid factor
- ULN, upper limit of normal
- rheumatoid arthritis
- leflunomide
- sulfasalazine
- efficacy
- safety
- clinical trials
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- ACR, American College of Rheumatology
- ALT, alanine aminotransferase
- DAS28, 28 joint count Disease Activity Score
- DMARD, disease modifying antirheumatic drug
- ESR, erythrocyte sedimentation rate
- ITT, intention to treat
- LOCF, last observation carried forward
- PMN, polymorphonuclear
- RA, rheumatoid arthritis
- RELIEF, Rheumatoid arthritis Evaluation of Leflunomide further Insights into its Efficacy
- RF, rheumatoid factor
- ULN, upper limit of normal