LB-0001 –
In Patients with Early RA who Failed Initial MTX, the Addition of Anti-TNF Yields Better EULAR and ACR Responses than the Additional of Conventional DMARDs: 1-Year Results of the SWEFOT Clinical Trial
Van Vollenhoven, Ernestam, Geborek, Peterson, Coster, Waltbrand, et al. Sweden.
Objective:
The aim of open, randomized, controlled study (the SWEFOT trial) was to compare the efficacy and safety of nonbiologic to biologic DMARDs in patients with inadequate responses to MTX monotherapy.
Methods:
487 patients with early RA (symptoms < 1 yr) were started on MTX at up to 20 mg/wk. 259 patients who had not achieved a DAS28 < 3.2 by 3-4 months were randomized to treatment A or B: (A) n=130, sulfasalazine (SSZ) 1000 mg bid + hydroxychloroquine (HCQ) 400 mg qd; (B) n=128, infliximab (INF) 3 mg/kg given at 0, 2, 6 weeks and then q 8 weeks. DMARD doses could be adjusted for tolerance, and frequency but not dosage of INF could be adjusted. A single switch was allowed within each treatment strategy: in group A, SSZ + HCQ could be replaced by cyclosporine A (2.5-5.0 mg/kg/day); and, in group B, INF could be replaced by etanercept 50 mg weekly. The primary outcome was EULAR good response at 12 months; secondary outcomes included EULAR moderate response and ACR responses. Analysis was by intention-to-treat (ITT).
Results:
Demographic characteristics and RA disease activity were equivalent in the two treatment arms. Mean disease duration was 6 mos, ~67% were RF+, mean HAQ was 1.3, mean DAS was 4.8. 26% of patients in Group A achieved a EULAR good response, compared to 42% in arm B, at 12 mos (p<0.01). EULAR total responders were 52% in Group A and 64% in Group B (p<0.05). ACR20/50/70 responses were 33%, 16%, and 8% in group A compared to 49, 29, and 13% in group B (p<0.05 for ACR20 and ACR50, NS for ACR70).
Conclusion:
The addition of anti-TNF therapy to MTX monotherapy was superior to SSZ+HCQ in patients who had an inadequate response to MTX monotherapy.
Editorial Comment:
This is an important study since it is the first head to head study comparing combination of non-biologic DMARDs with combination of non-biologic + biologic DMARDs in MTX inadequate responders. [Although the BeST trial had similar treatment arms, patients did not have to fail MTX first, and the doses of MTX used in the treatment arms varied significantly.] In the SWEFOT trial, anti-TNF treatment appeared to be superior to SSZ+HCQ, but the difference only appeared at 9 mos and was only statistically significant at 12 mos, which is somewhat surprising given the relative rapidity of action of INF. There is a significant weakness in this study, however. Although there was a randomization process for treatment, this was an open label trial so both patients (and physicians presumably) were aware of their treatment assignments. This could clearly bias the results if there is a pre-treatment expectation that one treatment is better than other. A study that is on-going in the U.S. [Treatment of Early Arthritis (TEAR) study] has a similar design except that treatment is blinded to patients and investigators. It will be interesting to see if the results mimic the SWEFOT trial.
