Biologics for the treatment of adult-onset still’s disease

ABSTRACT

Introduction: Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder of unknown etiology, and approximately 60–70% of patients develop a chronic form. Up to 20–30% of patients who are refractory to conventional therapy need biologic agents. Recently, anti-cytokine biologic agents according to pathophysiology have resulted in significant progress in the treatment of AOSD.

Area Covered: Due to rarity and heterogeneous features of the disease, treatment of AOSD is not based on the controlled study but on case-based retrospective data. Here, we review the current status of the pathogenesis, limitations of therapeutic guidelines and outcome measures, utility of biologic agents, and future perspectives for treatment.

Expert opinion: IL-1 inhibitors are more effective for systemic manifestations and IL-6 inhibitors for both joint disease and systemic features. Anti-TNF agents would be useful for patients with the pure rheumatoid subgroup. Systemic manifestations respond rapidly, but arthritis shows rather slow response. Clinical response must be obtained within 2 to 3 months, and biologics with different mechanisms of action are required for non-responders. For patients in prolonged remission, we need to try tapering of biologics. Randomized controlled studies, new therapeutic agents, and composite biomarkers are required to improve the outcome of patients with AOSD.

KEYWORDS:

• Adult-onset still’s disease
• treatment
• biologic
• anakinra
• tocilizumab
• anti-TNF
• canakinumab
• DMARD
• macrophage activation syndrome

Article Highlights

• Adult-onset Still’s disease (AOSD) develops into a chronic form of the disease in approximately 60-70% of patients. However, we are not able to differentiate patients who are likely to progress to chronic disease. When some important factors are capable of identifying patients who are at high risk for progression, physicians can treat them with a tight strategy including the early use of biologic agents.

• IL-1 inhibitors may be more efficient in systemic manifestations and IL-6 inhibitors in both joint involvement and systemic manifestations. Anti-TNF agents including their biosimilars must be reserved for patients with pure chronic rheumatoid-like pattern.

• It is very important to measure disease activity accurately during long-term follow up, but currently available biomarkers have limited value to detect variable manifestations of AOSD. Development of composite biomarkers to detect disease activity could support rational decision-making in the treatment of AOSD.

• New biological agents against IL-17 and IL-18 or small molecules against Jak-1/Jak-2 may introduce additional therapeutic options in AOSD.

• For the management of life-threatening complications such as MAS, general immune suppression and anti-cytokine therapies such as anti-IL-1 agents will be useful. The introduction of a biologic agent and its dosage needs to be individualized according to the status of each patient.

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Declaration of interest

DH Yoo is a scientific consultant of Celltrion, Inc. and on the speaker’s bureau of Celltrion, Inc. and Celltrion healthcare, and has received research grants from Celltrion, Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Peer reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.