Review of Biologics in Children With Rheumatic Diseases

Shabina Habibi; Athimalaipet V Ramanan

Disclosures

Int J Clin Rheumatol. 2012;7(1):81-93. 

In This Article

Anakinra

Being an IL-1 receptor antagonist, it competitively binds the IL-1 receptor, without inducing downstream stimulatory signaling. It is administered at a dose of 1–2 mg/kg (maximum 100 mg daily) by subcutaneous injection.

In an initial open-label trial of anakinra in 80 children with a polyarticular course of JIA, although overall it had only a modest effect on ACR-Pedi 30 response, 73% of children with SOJIA responded, as compared with 54% with combined polyarticular and oligoarticular subtypes.[31] In another study of 20 children with corticosteroid-dependent active SOJIA, 95% having previously received methotrexate, and 70% anti-TNF-α therapy, 15 (75%) improved.[32] However ACR-Pedi 30, 50 and 70 responses were only modest at 3 months; 55, 30 and 0% respectively, and at 6 months; 50, 25 and 10%. Corticosteroid dose was reduced by 15–78% in nine children. Four children stopped therapy due to lack of efficacy. Overall safety was acceptable.

Another multicenter double-blind placebo-controlled trial of 24 children with SOJIA was recently published.[33] Part one of the trial was placebo-controlled, where 12 children each received either anakinra or placebo for 1 month, to demonstrate a higher proportion of responders in the active treatment group. Part two was an open-label treatment, where all children received anakinra after 1 month. At the end of 1 month, significantly more children receiving anakinra (67%) responded as compared with those receiving placebo (8%). Ten children switched to anakinra in the open-label phase, of whom nine responded. Gene-expression profiles were studied in the blood, and their normalization was observed in responders. Tolerability and side effects were similar in the anakinra and placebo groups. However loss of response was observed in most of the patients over time. The study concludes that anakinra is efficacious at least in the short term.

The recent US/ACR guidelines propose treatment with anakinra as a first-line steroid-sparing drug.[34] It has short-term efficacy, but these responses are not usually sustained in the long term. It needs daily injections, which may be painful and lead to local injection-site reactions. Infections are also increased. In the multicenter trial, a total of 46 infections were reported. Most were minor respiratory tract infections. Three children developed varicella infection and two had vulval candidiasis. Atypical pneumonitis and urinary tract infection were also reported. In four children, the infections were considered serious. In a cohort of 33 children with SOJIA from three centers in the USA were treated with anakinra, one child developed macrophage activation syndrome (MAS).[35] However anakinra has also been reported to be effective in the treatment of MAS associated with SOJIA.[36–38] These factors may hamper its widespread use in SOJIA. However the favorable experience with anakinra is encouraging further studies of IL-1 inhibitors in SOJIA.

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