Canakinumab for the treatment of systemic juvenile idiopathic arthritis

Abstract

The introduction of methotrexate in the 1980s and of TNF-inhibiting agents and abatacept in the late 1990s led to a dramatic improvement in the outcomes of non-systemic categories of juvenile idiopathic arthritis. By contrast, the same treatment approaches had no strong impact on the outcome of systemic juvenile idiopathic arthritis (SJIA), and the main effective treatment in these patients remained glucocorticoids with their known side effects. Encouraging findings in small studies involving SJIA patients treated with IL-1 and IL-6 inhibitors led to large Phase III trials, and the results in these trials provide hope that substantial joint damage and disability seen in the majority of patients with persistent SJIA can be prevented. The purpose of this review is to discuss the safety and efficacy of the IL-1 and IL-6 inhibiting agents in SJIA with the main focus on canakinumab, a fully human monoclonal anti-IL-1β antibody.

Keywords::

• anti-IL-1β monoclonal antibody
• canakinumab
• IL-1
• systemic juvenile idiopathic arthritis

Financial & competing interests disclosure

AA Grom has received speaker/consulting fees from Novartis and Roche, and has been involved in research collaboration for NovImmune. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Canakinumab is a high-affinity, fully human monoclonal anti-IL-1β antibody of the IgG1/k isotype designed to bind and neutralize the activity of human IL-1β.

• Based on the results of two Phase III clinical trials, canakinumab has been approved for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in the US and EU.

• In SJIA with active systemic features, canakinumab provided clinically meaningful response rates.

 – Almost half of the patients showed rapid response with marked improvement at American College of Rheumatology 90 level.

 – Clinical remission occurred in one-third of the patients.

 – There was a sustained therapeutic effect.

 – It was efficacious on arthritic as well as systemic components.

• Infections were the most common adverse event.

• Risk for macrophage activation syndrome in SJIA patients treated with canakinumab was not increased, but there was no full protection, even in patients whose underlying SJIA was well controlled.

Notes

^†Active arthritis on physical examination was defined as non-bony swelling or limitation of motion with either pain on motion or tenderness to palpation.

Adapted ACR pediatric 30/50/70 criteria of response are defined as: improvement of 30/50/70% in ≥3 of the first six response variables listed in Box 1, no more than one response variable worsening by ≥30% and no intermittent fever in the week preceding the response measurement.