Background EULAR guidelines for RA1 recommend adding a biologic disease-modifying antirheumatic drug (bDMARD) to a conventional synthetic DMARD (csDMARD) like methotrexate (MTX) if poor prognostic factors are present or response to csDMARD treatment alone is insufficient. If a first bDMARD fails, another bDMARD should be used, such as switching from one tumor necrosis factor inhibitor (TNFi) to another TNFi. It is not known whether antibodies to one TNFi influence the effectiveness of a different TNFi.
Objectives This phase 4, single-arm study evaluated the efficacy and safety of ETN in adult RA patients who had failed ADA.
Methods Adults (age ≥18 years) with moderate to severe RA (disease activity score using 28-joint count and C-reactive protein [DAS 28-CRP] ≥3.2) who failed to respond to ADA+MTX (1° ADA failure) or lost a satisfactory response to ADA+MTX (2° ADA failure) were enrolled. After ≥2 weeks without ADA, ETN 50 mg once weekly for 24 weeks was added to ongoing MTX treatment. Visits occurred at weeks 0, 4, 8, 12, 18, and 24. Assessments included American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) improvement criteria, and DAS28-CRP. The primary efficacy endpoint was ACR20 at week 12.
Results Of 85 patients who received ETN, 80% were women; mean age was 56.6 years. Overall, 28% had anti-ADA antibodies (42% were neutralizing and 58% non-neutralizing), including 21% (7/33) with 1° ADA failure and 33% (17/52) with 2° ADA failure. Median duration of prior ADA therapy was 46 weeks (range, 12–466 weeks). Of 84 evaluable patients, 30 (36%) achieved ACR20 at week 12 (95% confidence interval [CI]: 26%, 47%) and 29 (35%) achieved ACR20 at week 24. The rates for ACR50 and ACR70 with ETN were 11% and 2%, respectively, at week 12, and 16% and 4%, respectively, at week 24. ACR20 rates by visit are shown by subgroup in the figure. Of the subgroups, patients with 2° ADA failure and anti-ADA antibodies were most likely to have an ACR20 response with ETN at week 12 (65%; odds ratio vs no anti-ADA antibodies 5.2; 95% CI: 2.0, 13.5; P <0.001). DAS28-CRP improved by a mean of 0.8–2.0 in each subgroup at week 12 of ETN, with the greatest improvement in patients with anti-ADA antibodies and 2° ADA failure. Most patients (82%) in this subgroup had DAS28-CRP improvement ≥1.2 at week 12 of treatment with ETN. ACR20 responses at week 12 occurred in patients with anti-ADA binding antibodies that were either neutralizing (4/10; 40%) or non-neutralizing (8/14; 57%). Safety results (≥1 adverse event in 73% of patients and no fatal adverse events) were consistent with the known safety profile of ETN.
Conclusions In patients who fail ADA, ETN could be considered as a therapeutic option. The presence of anti-ADA antibodies in patients with 2° ADA failure may guide treatment decisions.
Smolen JS, et al. Ann Rheum Dis. 2014;73:492–509.
Acknowledgement Amgen supported this work. Julie Wang (Amgen) and Jonathan Latham (on behalf of Amgen) assisted with the preparation of the abstract.
Disclosure of Interest L. Bessette Grant/research support from: Amgen Inc., M. Khraishi: None declared, A. Kivitz: None declared, A. Kaliyaperumal Shareholder of: Amgen Inc., Employee of: Amgen Inc., R. Grantab Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. Poulin-Costello Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.