Treatment with etanercept plus methotrexate has been shown to be effective in patients with rheumatoid arthritis (RA). Sulfasalazine is widely prescribed for the treatment of RA; however, it is not known whether etanercept plus sulfasalazine would be an effective treatment for RA.OBJECTIVE
The object of this study was to determine whether patients with an inadequate response to sulfasalazine would benefit from adding etanercept to their sulfasalazine regimen, or from switching to etanercept.DESIGN
This was a double-blind, randomized, parallel, multicenter study. Patients were eligible for inclusion if they had active RA, were 18 years old or over, had disease duration of 20 years or fewer, and were receiving stable doses of sulfasalazine for at least 4 months without an adequate response, and without toxicity. Exclusion criteria were presence of relevant comorbidity, previous treatment with etanercept or other tumor necrosis factor (TNF) inhibitors, treatment with a DMARD (disease-modifying anti-rheumatic drug) other than sulfasalazine 3 months before the study, treatment with immunosuppressive biologic agents or cyclophosphamide 6 months before the study, and treatment with parenteral corticosteroids 4 weeks before the study.INTERVENTION
Patients were treated for 24 weeks with etanercept 25 mg subcutaneously twice weekly plus oral placebo daily, placebo subcutaneously twice weekly and sulfasalazine tablets daily, or etanercept 25 mg subcutaneously twice weekly plus sulfasalazine tablets daily. Patients continued previous doses of sulfasalazine (2, 2.5 or 3 g daily), and were permitted treatment with oral corticosteroids, one NSAID, aspirin, or simple analgesics with no anti-inflammatory activity.OUTCOME MEASURES
The primary outcome measure was the percentage of patients achieving a 20% improvement in the American College of Rheumatology (ACR) criteria (ACR20) at week 24. Secondary outcome measures included 50% and 70% improvement in the ACR criteria (ACR50 and ACR70, respectively).RESULTS
In total, 254 patients received at least one dose of the study treatment: 103 patients received etanercept alone, 50 patients received sulfasalazine alone and 101 patients received etanercept plus sulfasalazine. Seventeen patients discontinued treatment, including 12 from the sulfasalazine alone group. Lack of efficacy was the main cause of discontinuation. At week 24, ACR20 was achieved by 73.8 %, 28.0 % and 74.0 % in the etanercept alone, sulfasalazine alone, and etanercept plus sulfasalazine groups, respectively. Significantly more patients in the etanercept groups achieved ACR50 and ACR70 responses at week 24 than the sulfasalazine alone group (P<0.01). Adverse events including headache, nausea and asthenia were lower in the etanercept alone group than in the etanercept plus sulfasalazine group, but infections and injection-site reactions were more common in the etanercept alone group than in the other two groups.CONCLUSION
Etanercept, with or without concomitant sulfasalazine, improved the signs and symptoms of RA in patients who had active disease despite previous treatment with sulfasalazine. Patients with an inadequate response to sulfasalazine can be switched from sulfasalazine to etanercept.