Single-Arm Study of Etanercept in Adult Patients with Moderate to Severe Rheumatoid Arthritis Who Failed Adalimumab Treatment

Louis Bessette, Majed Khraishi, Alan J Kivitz, Arunan Kaliyaperumal, Rama Grantab, Melanie Poulin-Costello, Maya Isaila, David Collier, Louis Bessette, Majed Khraishi, Alan J Kivitz, Arunan Kaliyaperumal, Rama Grantab, Melanie Poulin-Costello, Maya Isaila, David Collier

Abstract

Introduction: To evaluate the efficacy and safety of etanercept treatment in adult patients with moderate to severe rheumatoid arthritis (RA) who failed to respond (primary failure) or lost a satisfactory response (secondary failure) to adalimumab.

Methods: All patients discontinued prior adalimumab treatment and continued methotrexate with etanercept 50 mg once weekly for 24 weeks. The primary study endpoint was American College of Rheumatology 20% improvement criteria (ACR20) at week 12.

Results: Eighty-five patients (mean age 56.6 years; female 80.0%) were evaluated for safety and 84 for efficacy. Thirty (35.7%) patients achieved ACR20 at week 12; the lower bound of the 95% confidence interval (CI; 25.6, 46.9) was greater than the prespecified goal of 24% based on previous research. Improvements from baseline in clinical outcomes and patient-reported outcomes were observed at each study visit. In planned subgroup analyses, patients with anti-adalimumab antibodies and secondary adalimumab failure had the highest ACR20 response to etanercept at week 12 (11/17 patients; 64.7%). Among the patients with secondary adalimumab failure, those with anti-adalimumab antibodies were fivefold more likely to have an ACR20 response to etanercept than those without anti-adalimumab antibodies (odds ratio 5.2; 95% CI 2.0, 13.5; P < 0.001). Adverse events were reported for 62 (72.9%) patients and were consistent with previous studies of etanercept. Most adverse events were mild or moderate in severity.

Conclusion: Switching to etanercept is a therapeutic option in patients with RA who fail adalimumab treatment. The presence of anti-adalimumab antibodies may provide additional support for switching to etanercept, particularly in patients with secondary adalimumab failure.

Trial registration: ClinicalTrials.gov identifier, NCT01927757.

Keywords: Adalimumab; Antibodies; Antirheumatic agents; Etanercept; Humanized; Monoclonal; Receptors; Rheumatoid arthritis; Tumor necrosis factor.

Figures

Fig. 1
Fig. 1
Flow diagram of patient enrollment and disposition
Fig. 2
Fig. 2
Etanercept efficacy at week 12, overall and by anti-adalimumab (ADA) antibody status and ADA failure type. Error bars are the 95% confidence interval. The primary study endpoint, American College of Rheumatology 20% improvement criteria (ACR20) at week 12, was achieved by 35.7% of patients; the lower bound of the 95% confidence interval (CI) was >24%. Missing data were imputed as ACR20 nonresponse. 1°/2° indicates primary/secondary ADA failure. Dagger symbol indicates that of the 84 patients evaluable for efficacy, anti-ADA antibody status was not tested for 5 patients (4 with primary ADA failure and 1 with secondary ADA failure)

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