Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial

Abstract

Objective: To investigate the efficacy and safety of abatacept in combination with etanercept in patients with active rheumatoid arthritis during a 1-year, randomised, placebo-controlled, double-blind phase, followed by an open-label, long-term extension (LTE). Methods: Patients continued etanercept (25 mg twice weekly) and were randomised to receive abatacept 2 mg/kg (n = 85) or placebo (n = 36). As the effective dose of abatacept was established as 10 mg/kg in a separate trial, all patients received abatacept 10 mg/kg and etanercept during the LTE. Results: A total of 121 patients were randomised; 80 completed double-blind treatment and entered the LTE. During double-blind treatment, the difference in the percentage of patients achieving the primary end point (modified American College of Rheumatology (ACR) 20 response at 6 months) was not significant between groups (48.2% v 30.6%; p = 0.072). At 1 year, no notable changes in modified ACR responses were observed. Subsequent to the dosing change, similar modified ACR responses were seen during the LTE. Significant improvements in quality of life were observed with abatacept and etanercept versus placebo and etanercept in five of the eight short-form 36 subscales at 1 year. More abatacept and etanercept-treated patients experienced serious adverse events (SAEs) at 1 year than patients receiving placebo and etanercept (16.5% v 2.8%), with 3.5% v 0% experiencing serious infections. Conclusion: The combination of abatacept (at a dose of 2 mg/kg during the double-blind phase and 10 mg/ kg during the LTE) and etanercept was associated with an increase in SAEs, including serious infections, with limited clinical effect. On the basis of the limited efficacy findings and safety concerns, abatacept in combination with etanercept should not be used for rheumatoid arthritis treatment.

Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

“…However, clinical trials simultaneously inhibiting 2 cytokines, TNF and IL‐17A, with biologics have not been reported in patients with PsA. In RA patients, combination therapy involving TNF inhibitors combined with biologic agents that engage other targets, including IL‐1 23, T cells 24, 25, and B cells 26, was associated with an increase in serious adverse events (AEs), including serious infections, and little or no efficacy benefit compared to treatment with a TNF inhibitor alone 23, 24, 25, 26.…”

Biological Therapy and Infection in Rheumatoid Arthritis Patients: Modern Aspects

“…При оценке безопасно-сти АБЦ в реальной клинической практике (исследование ASSURE) частота СКИ достоверно не отличалась от кон-троля (2,9 и 1,9% соответственно) [21]. Продемонстриро-вано нарастание частоты СКИ при комбинации АБЦ с иФНО-α [22]. В целом при оценке 8 крупных РКИ частота развития СИ при внутривенном (в/в) введении АБЦ была выше, чем в контроле (5,5% и 2,0%, ОР 3,68 и 2,6 соот-ветственно) и снижалась при более длительном (>1 года) периоде наблюдения (ОР 2,87) [23].…”

Combination Biologic Treatment of Refractory Psoriasis and Psoriatic Arthritis

“…There were no differences regarding safety at 6 months, but after 1 year there was a significant increase in the prevalence and frequency of serious adverse events, and combination therapy was stopped. Both Weinblatt, et al 13 …”

“…Weinblatt and colleagues 13 conducted a pilot phase IIb trial to evaluate the safety and clinical efficacy of abatacept 2 mg/kg plus etanercept 25 mg twice weekly in 121 patients with active RA despite continued etanercept Figure 1D. Abdominal and right upper extremity exhibiting extensive skin involvement prior to combination therapy.…”