Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of Adult-Onset Still’s Disease with Liver Failure with No Response to Tocilizumab Therapy

A 21-year-old woman with refractory systemic flare of adult-onset Still’s disease with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus, and tocilizumab, was successfully treated with additional use of etanercept. Etanercept at a dose of 50？mg weekly was partially effective but could not reduce the dose of concomitant betamethasone from 5？mg/day. Etanercept at a dose of 75？mg weekly could lead her to clinical remission and enabled successful tapering off the corticosteroids and discontinuation of etanercept. Normalization of serum C-reactive protein and interleukin 6 and persistent elevation of serum tumor necrosis factor α under the treatment with high-dose corticosteroids and immunosuppressants suggest that tumor necrosis factor α was more deeply involved than at least interleukin 6 in the pathogenesis of refractoriness of the disease in this patient, and these findings might be indicative of potential efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an interleukin 6 inhibitor. 1. Introduction Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease characterized by spike fevers, evanescent rash, and polyarthritis [1, 2]. Although systemic flares of the disease may be usually successfully treated with high-dose corticosteroids with or without immunosuppressants, refractory systemic flares of the disease may potentially cause life-threatening conditions, such as macrophage activation syndrome and hepatic failure [1–4]. The biologic agents that selectively inhibit the action of proinflammatory cytokines such as tumor necrosis factor α (TNFα), interleukin (IL) 1, and IL6 have been successfully used for the treatment of AOSD refractory to conventional therapies that in turn reinforce the importance of excess of proinflammatory cytokines in the pathogenesis of AOSD [1, 2]. Several case reports regarding efficacy of switching biologics in AOSD suggest that effective targets for cytokine inhibitors are different among individual patients and in turn mirror the fact that cytokines with the more dominant role in maintaining the refractoriness of AOSD to conventional therapy are different [2, 5–7]. Here, we report a patient with systemic flare of AOSD with no response to treatment with high-dose corticosteroids, immunosuppressants, and anti-IL6 receptor antibody, tocilizumab, and successfully treated with higher-dose soluble TNFα receptor agent, etanercept, in conjunction with the results of serum levels of C-reactive protein (CRP) and proinflammatory cytokines. 2. Case Presentation A previously