Orencia vs Enbrel (Abatacept Vs Etanercept) – Comparison

Orencia vs Enbrel is a comparison of the two TNF inhibitors, Abatacept and Etanercept. Both drugs are being used to treat autoimmune rheumatic conditions, primarily Rheumatoid arthritis.

Orencia and Enbrel both are indicated in chronic inflammatory conditions. Orencia (Abatacept) is a disease-modifying antirheumatic drug (DMARDs) use for the treatment of rheumatoid arthritis and active juvenile idiopathic arthritis.

Enbrel (Etanercept) is a protein therapy that acts by the binding fragment of TNF-α receptor to treat rheumatoid arthritis and plaque psoriasis.

Orencia vs Enbrel (Abatacept Vs Etanercept): Indications

Pharmacokinetics of Orencia vs Enbrel (Abatacept Vs Etanercept):

Mechanism of action of Orencia vs Enbrel (Abatacept Vs Etanercept):

Orencia (Abatacept) MOA:

• Abatacept is a costimulation modulator, it is known to inhibit T-cell activation by binding to CD80 & CD86 and blocks its interaction with CD28. This in turn inhibits the autoimmune activation of T-cells, which is involved in the pathogenesis of Rheumatoid arthritis and juvenile idiopathic arthritis.

Enbrel (Etanercept) MOA:

• Etanercept is a dimeric molecule in the soluble form of TNF receptor p75. It binds to two molecules of TNF thereby removing them from circulation. TNF is involved in inflammatory and immune responses. High levels of TNF are found in tissues and fluids of RA patients and other autoimmune conditions. By binding to TNF molecules etanercept reduces levels of TNF in circulation which aids in reducing disease symptoms.

Orencia vs Enbrel (Abatacept Vs Etanercept) efficacy in different disease conditions

Orencia vs Enbrel (Abatacept Vs Etanercept) in Rheumatoid arthritis:

Orencia (Abatacept):

• Orencia (Abatacept) is a fusion protein. It is composed of the Fc region of IgG1 that is fused to CTLA4. It plays a role in the prevention of T-cell activation. It is the only T-cell targeting therapy for Rheumatoid Arthritis.
• Abatacept has been an effective treatment in slowing down the progression of disease in RA patients. In one clinical trial, a randomized phase II study was performed to assess the efficacy of IV abatacept in patients with rheumatoid arthritis.
• The dosage received by patients was 0.5mg/kg, 2mg/kg and 10mg/kg. The highest response rate was observed in patients receiving 10mg/kg. A greater response was achieved from 10mg/kg and it also met ACR20 improvement criteria. This suggests that abatacept therapy may slow or alter the progression of RA at early stages.[Ref]
• Another Phase II study was conducted to assess the efficacy of abatacept and etanercept combination therapy, but it showed an increased risk of adverse side effects that’s why abatacept in combination with etanercept is not recommended.[Ref]
• Abatacept therapy in combination with methotrexate is more efficacious than methotrexate monotherapy. It has been beneficial in disease remission and slow progression. The SC dosage is more efficacious and has low immunogenicity than the IV dose of abatacept. Abatacept therapy is also beneficial in patients who have not previously responded to TNF inhibitors.[Ref]
• Abatacept therapy is associated with a 17% increased risk of cancer than other drugs, that’s why it must be used with great caution.[Ref]

Enbrel (etanercept):

• Enbrel (Etanercept) is a fusion protein that consists of the extracellular portion of p75 receptor fused to the Fc region of IgG1 with high affinity. This high-affinity binding neutralizes the activity of TNF- α. Several clinical trials have analyzed the efficacy of Enbrel in rheumatoid arthritis. Treatment with etanercept has the greatest improvements.
• In a study, 75 to 57% of patients achieved ACR20 and ACR50 response in a 3 months treatment duration. A significant reduction in tender or swollen joints was observed to 61%. Short-term studies suggest that with treatment discontinuation the activity of disease reverted to baseline values. But long-term studies show a beneficial impact on disease remission.[Ref]
• Etanercept in combination with methotrexate is more beneficial in the treatment of RA. Only patients who do not respond well to monotherapy should receive the combination therapy according to the National Guidelines Recommendations.
• Clinical data on the use of etanercept for treatment of RA in elderly patients suggests that there is no difference in efficacy of etanercept in any age group however the risk of serious events is significantly higher in elderly patients.[Ref]

Read: TNF Inhibitors; An Overview of Their Use in Immune-mediated Diseases

Orencia vs Enbrel (Abatacept Vs Etanercept) Use in Psoriatic arthritis:

Orencia (Abatacept):

• Abatacept is also effective in the treatment of psoriatic arthritis. In a clinical trial, abatacept was studied in phase I, II, and III studies in both the treatment of Psoriasis and Psoriatic Arthritis. It showed a 50% or greater improvement in disease activity. After the administration of abatacept, a reduction in CD8+T cell and CD4 cells was observed. Overall disease activity was also significantly improved.[Ref]
• Another study conducted to assess the efficacy of abatacept in PsA suggested that abatacept therapy was associated with a reduction in MRI score of bone marrow osteitis, bone erosion, and synovitis.

Enbrel (Etanercept):

• Clinical trials assessing the efficacy of etanercept in Psoriatic arthritis suggest a rapid improvement response in patients. Etanercept is found to be effective on the skin lesions, ETN reduced all the measures of disease activity as well as ACR20, ACR50, and ACR70
• One study assessed the comparative efficacy of infliximab and etanercept that suggested etanercept was no inferior to infliximab and there were higher discontinuation rates associated with infliximab therapy.[Ref]
• In patients with RA etanercept is known to reduce the incidence of CVD risk factors.[Ref]

Read: Biologics for Psoriasis (TNF, IL-23, IL-39, IL-17, and CD-6 Inhibitors)

Orencia vs Enbrel (Abatacept Vs Etanercept) Use in Juvenile Idiopathic Arthritis:

Orencia (Abatacept):

• The effectiveness of subcutaneous and intravenous doses of abatacept was studied in children with RF-positive and negative polyarticular arthritis, systemic arthritis, and extended oligoarthritis. All of the children achieved 63-68% JIA-ACR30 response after 4 months and all these categories responded early to abatacept. Both SC and IV doses were equally efficacious.
• In one study the effect of abatacept on the growth and development of children was studied, the results concluded that abatacept therapy improved growth and development even in the most impaired children. The sexual maturation of female children was not affected however, limited data is available on its effect on male sexual maturation.[Ref]

Enbrel (Etanercept):

• In the pediatric population, Etanercept use is safe and effective for the achievement of clinical outcomes. In a clinical trial on the efficacy of Etanercept in JIA patients, TNF-α inhibition resulted in a reduction of IL-6 and IL-8 with clinical improvement. These findings confirmed the long-term efficacy of Etanercept in the treatment of children with JIA.[Ref]
• In another open-label trial, efficacy and safety of etanercept were studied for 6 years. Etanercept was found effective in improving all disease symptoms with no serious adverse events for a duration of 6 years. Common side effects included diarrhea, headaches, and upper respiratory tract infections.[Ref]

Read: Simponi vs Enbrel (Golimumab Vs Etanercept); Comparison

Conclusion:

Enbrel is a better treatment choice in the the treatment of Rheumatoid Arthritis, Juvenile idiopathic arthritis, and Psoriatic arthritis due to greater efficacy and low risk of adverse side effects.