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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Jul 22;64(1):44–51. doi: 10.1136/ard.2003.016709

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

M Dougados 1, P Emery 1, E Lemmel 1, C Zerbini 1, S Brin 1, P van Riel 1
PMCID: PMC1755199  PMID: 15271770

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.

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Figure 1.

Figure 1

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 RELIEF study design.

Figure 2.

Figure 2

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 Expected and observed DAS28 response rates at the end of the study (week 24 or LOCF) and DAS28 response rates for week 24 completers (A) and sustained DAS28 responders by study visit (B). LEF, leflunomide; SSZ, sulfasalazine; PLC, placebo.

Figure 3.

Figure 3

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 ACR 20%, 50%, and 70% responses at the end of the study (week 24 or LOCF) (A) and sustained ACR 20% responders by study visit (B). LEF, leflunomide; SSZ, sulfasalazine; PLC, placebo.

Figure 4.

Figure 4

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 Possibly related adverse events reported in >5% of patients. LEF, leflunomide; SSZ, sulfasalazine; PLC, placebo; LFT, liver function test; GI, gastrointestinal; WBC, white blood cell.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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