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

Abstract

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.

Figure 1

Patient's treatment, liver function, and inflammatory biomarkers during the clinical course. ALT, alanine aminotransferase; CRP, C-reactive protein; CyA, cyclosporine; Dex-Pal, dexamethasone palmitate; ETN, etanercept; HD-IVIg, high-dose intravenous immunoglobulin therapy; IFN, interferon; IL, interleukin; mPSL, methylprednisolone; PSL, prednisolone; RIND (betamethasone), sIL2-R, soluble interleukin 2 receptor; TAC, tacrolimus; TCZ, tocilizumab. Cytokines were measured by SRL Inc. with the following kits; TNFα, Quantikine HS Human TNF-α immunoassay (R&D); interferon-γ, IFN-γ Human Direct ELISA Kit (Life Technologies Japan); IL1β, IL-1β Human ELISA Kit (Life Technologies Japan); IL6 Lumipulse human IL6 (Fuji Rebio); IL18, Human IL-18 ELISA kit (MBL). Reference values are as follows: TNFα (normal < 2.8 pg/mL), IFNγ (normal < 0.1 pg/mL), IL1β (normal < 10 pg/mL), IL6 (normal < 4 pg/mL), IL18 (normal < 259.4 pg/mL).