Effectiveness of subcutaneous tocilizumab in refractory adult Still’s disease: report of three cases and a review of the literature

Abstract

Adult Still’s disease (ASD) is a systemic inflammatory disorder characterised by spiking fever, skin rash, arthritis, hepatosplenomegaly, and elevated inflammatory markers. Several proinflammatory cytokines, including interleukin (IL)-6, contribute to its pathogenesis. There have been some recent reports on the efficacy of tocilizumab (TCZ), a humanised anti-IL-6 receptor antibody, in the treatment of ASD refractory to conventional therapy. However, most of the evidence is for intravenous administration of TCZ, whereas subcutaneous injection is often preferred in terms of efficiency in cost and labour. We have experienced three patients whose ASD was refractory to corticosteroid and immunosuppressant therapy but showed a marked response to off-label use of subcutaneous TCZ (TCZ-SC). Patient 1 received TCZ-SC 162 mg on days 0 and 14 and every week thereafter. Patients 2 and 3 received TCZ-SC every 2 weeks. At the time of initiation of TCZ-SC, all three patients had elevated inflammatory markers and two had fever despite previous therapy. After the first TCZ-SC injection, the patients became afebrile within one day and inflammatory parameters (i.e. C-reactive protein and erythrocyte sedimentation rate) returned to normal within 2 weeks. None of the patients developed severe infection or other serious side effects during 104 weeks of follow-up. There have been only a limited number of case reports showing that TCZ-SC significantly improves refractory ASD during its active phase. Our experience with these patients suggests that TCZ-SC could, as well as offering cost efficiency in clinical practice, be a potent treatment option for refractory ASD.

Keywords:

• Adult Still’s disease
• tocilizumab
• IL-6
• remission
• corticosteroid-sparing effect

Patient consent

All patients in this series provided written informed consent for their clinical details to be published.

Ethical approval

This study was conducted according to the principles expressed in the Helsinki Declaration of 1983 and was approved by the Ethics Committee of Oita University Faculty of Medicine (approval number: 1976).

Conflict of interest

None.