A study to evaluate the efficacy and safety of Etanercept in patients with moderately active rheumatoid arthritis despite DMARD therapy

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A study to evaluate the efficacy and safety of Etanercept in patients with moderately active rheumatoid arthritis despite DMARD therapy
Key Take-Away: 
  • The results of this study revealed a trend toward better clinical outcomes in patients on etanercept plus methotrexate therapy compared with methotrexate alone.
  • More evidence is needed before reaching any clinical recommendations.

The American College of Rheumatology (ACR) recommends using disease-modifying antirheumatic drugs (DMARDs) or biologic agents in treating patients with early rheumatoid arthritis (RA) and established RA. Etanercept, a modified p75 receptor of tumor necrosis factor (TNF) that inhibits the action of TNF, has been shown to be efficacious for the treatment of moderate to severe RA in patients with early and established disease.

ABSTRACT: 
Background: 

The American College of Rheumatology (ACR) recommends using disease-modifying antirheumatic drugs (DMARDs) or biologic agents in treating patients with early rheumatoid arthritis (RA) and established RA. Etanercept, a modified p75 receptor of tumor necrosis factor (TNF) that inhibits the action of TNF, has been shown to be efficacious for the treatment of moderate to severe RA in patients with early and established disease. Subgroup data of patients with moderately active disease has shown to achieve better disease status (LDA or remission) with etanercept treatment than patients with more severe disease. However, there is paucity of supporting evidence highlighting the need of a prospective trial of etanercept in patients with moderately active disease.

 

Rationale behind research

  • Subgroup data of patients with moderately active disease has shown to achieve better disease status (LDA or remission) with etanercept treatment than patients with more severe disease. However, there is a paucity of such evidence.
  • The need of a prospective trial of etanercept in patients with moderately active disease led to conduction of this trial.
  • Objective

To evaluate the efficacy and safety of adding etanercept to disease-modifying anti-rheumatic drugs (DMARDs) in patients with moderately active rheumatoid arthritis (RA)

Methods: 

 

Study outcomes

  • Primary outcome: Low disease activity (LDA) at week 12
  • Secondary outcomes: DAS28-CRP remission at week 12;rates of Clinical Disease Activity Index (CDAI) LDA (score ≤ 10) and remission (score ≤2.8); rates of Simplified Disease Activity Index (SDAI) LDA (score ≤11) and remission (score ≤3.3); rates of 20%, 50%, and 70% improvement in ACR criteria (ACR20, ACR50, and ACR70); changes in Health Assessment Questionnaire Disability Index (HAQ-DI), safety and adverse effects
  • Time-points
    • Efficacy: Baseline, weeks 2,4,8,12,16,20, & 24
    • Patient reported outcomes: Baseline, weeks 2,4,8,12,16,20, & 24
    • Safety: Additional 4 weeks follow up post 24 weeks of study(12 weeks randomized phase + 12 weeks single arm phase)
Results: 

 

  • Baseline: Patients required moderate disease activity for enrollment in the study. However, at baseline only 122 patients (58%) had moderate disease when administration of study drugs was initiated. Most patients were women (77%), most were white (86%)
  • At week 12, 33% on etanercept and 21% on placebo achieved LDA (P = 0.055); remission was achieved in 19% and 12%, respectively (P = 0.14)
  • At week 12, ACR20, ACR50, and ACR70 responses were observed in 29%, 13%, and 1% respectively, in patients on placebo, and 41%, 21%, and 6% of patients on etanercept
  • Mean (SD) change from baseline in HAQ-DI score was −0.20 (0.43) for placebo patients and −0.39 (0.54) for etanercept patients at week 12.
  • During the 12-week, double-blind portion of the study, 61% of patients in the placebo-etanercept group and 67% of the etanercept-etanercept group reported an adverse event (AE). The most commonly reported AEs through week 12 included injection site erythema (1.0% placebo etanercept; 11.3% etanercept-etanercept), headache (10.6%; 7.5%), injection site pruritus (1.9%; 6.6%), and injection site rash (1.0%; 6.6%)
  • Overall, 78% of all patients reported an AE through 24 weeks of treatment
Conclusion: 

The result indicates that low disease activity (LDA) was achieved by more patients on etanercept than placebo in patients with moderate disease at screening, but the difference was not statistically significant at week 12.

Patients with moderate disease have been shown to achieve better clinical responses to etanercept therapy than patients with severe disease (Keystone et al. 2009). The results of this study revealed a trend toward better clinical outcomes in patients on etanercept plus methotrexate therapy compared with methotrexate alone. Within the spectrum of moderately active disease, changes in status (i.e., moderate to severe disease) can be frequent and disease activity scores at any given time may not accurately reflect these changes. Protocols do not confirm the hypothesis, it may offer results that are clinically significant but difficult to reconcile. Moreover, they also provide information for improving the designs of future studies.

Springer Plus 2015; 4:113
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