Canakinumab for the treatment of adult-onset Still’s disease

ABSTRACT

Introduction: Adult-onset Still’s disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology, with clinical and biological similarities with the juvenile form (sJIA).

The pivotal role of interleukin (IL)-1 gives rise to the use of IL-1 inhibitors in treating resistant cases.

Areas covered: This review focuses on canakinumab, a fully human anti-IL-1β antibody, as treatment for AOSD. The data obtained from case reports and case series on AOSD and two double-blind, randomized, placebo-controlled Phase III trial on sJIA are analyzed. Efficacy and safety profiles of canakinumab are discussed.

Expert opinion: There is no unanimous consensus on how to treat with IL-1 inhibitors. Many reviews have focused primarily on anakinra, but the accumulating data for canakinumab have emerged. The choice of treatment is a relevant issue for patients and the national health services. The available data for canakinumab indicate that this drug in AOSD patients is effective and well tolerated.

KEYWORDS:

• Canakinumab
• adult-onset still’s disease
• systemic juvenile idiopathic arthritis
• autoinflammatory diseases
• IL-1
• anakinra
• rilonacept
• treatment

Article highlights

• AOSD is a complex and heterogeneous autoinflammatory disorder.

• The pathogenesis of AOSD is not completely known, but some of the key proinflammatory cytokines (IL-1, IL-18, IL-6, and TNF-α) are involved.

• Anti-IL-1 treatments are very effective in IL-1 driven diseases. Three IL-1 inhibitors are now available in the market: anakinra, an analog of the natural IL-1 receptor antagonist; rilonacept, an IL-1 receptor fusion protein; and canakinumab, a selective fully human IL-1 β monoclonal antibody.

• Since canakinumab has the longest half-life among the three, it can be injected subcutaneously at a recommended interval of every 4 weeks in a dosage of 4 mg/kg (max 300 mg)

• The data obtained from case series in AOSD suggest that canakinumab is an effective and a safe treatment in corticosteroid and DMARD-refractory patients.

• The only clinical trial (phase II, placebo-controlled) with CANA in AOSD has stopped early due to recruitment issues. Previously, three phase III studies on sJIA confirmed the efficacy and safety of CANA in children.

• Considering the concept of a Still’s disease continuum, both older adolescents with sJIA and young adults with AOSD may benefit from IL-1 inhibition with CANA.

Declaration of interest

P Sfriso has received a research grant and conference support from Novartis Pharmaceutical Corporation and Swedish Orphan Biovitrum. The authors have 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.

Reviewer disclosures

A peer reviewer on this manuscript has disclosed having received unrestricted funding for clinical studies and personal payments for presentations and advisory board membership from Novartis. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.