When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to continuing leflunomide?

• Published in: Annals of the rheumatic diseases 2005-01, Vol.64 (1), p.44-51
• Main Authors: Dougados, M, Emery, P, Lemmel, E M, Zerbini, C A F, Brin, S, van Riel, P
• Format: Article
• Language: English
• Subjects: 28 joint count Disease Activity Score; ACR; Adolescent; Adult; Aged; alanine aminotransferase; ALT; American College of Rheumatology; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Clinical medicine; clinical trials; DAS28; disease modifying antirheumatic drug; Diseases of the osteoarticular system; DMARD; Double-Blind Method; Drug dosages; Drug Therapy, Combination; efficacy; erythrocyte sedimentation rate; ESR; Extended Report; Female; Humans; Inflammatory joint diseases; intention to treat; Isoxazoles - adverse effects; Isoxazoles - therapeutic use; ITT; last observation carried forward; leflunomide; LOCF; Male; Medical sciences; Middle Aged; PMN; polymorphonuclear; RELIEF; Rheumatoid arthritis; Rheumatoid arthritis Evaluation of Leflunomide further Insights into its Efficacy; rheumatoid factor; Rheumatology; safety; Studies; sulfasalazine; Sulfasalazine - adverse effects; Sulfasalazine - therapeutic use; Treatment Failure; Treatment Outcome; ULN; upper limit of normal
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2003.016709

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.