Mechanism of Action: Canakinumab is a human IgG1/κ monoclonal antibody against IL-1β. It forms a complex with IL-1β, preventing its binding to IL-1 receptors.
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Pharmacokinetics: Canakinumab is given by subcutaneous injection. It reaches peak serum concentrations 7 days after a single subcutaneous injection. Canakinumab has an absolute bioavailability of 66% and a 26-day mean terminal half-life. The recommended dose for patients with SJIA who weigh more than 7.5 kg is 4 mg/kg every 4 weeks. There is a weight-adjusted algorithm for treating CAPS.
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Indications: Canakinumab is indicated for active SJIA in children 2 years or older. As noted, it is also used to treat CAPS, particularly the familial cold autoinflammatory syndrome and Muckle-Wells syndrome subtypes for adults and children 4 years or older. Canakinumab is also used to treat gout (see below).
1. Mechanism of Action: Rilonacept is the ligand-binding domain of the IL-1 receptor. It binds mainly to IL-1β and binds with lower affinity to IL-1α and IL-1RA. Rilonacept neutralizes IL-1β and prevents its attachment to IL-1 receptors.
2. Pharmacokinetics: The subcutaneous dose of rilonacept for CAPS is age-dependent. In patients 12–17 years of age, 4.4 mg/kg (maximum of 320 mg) is the loading dose, with a maintenance dose of 2.2 mg/kg (maximum of 160 mg) weekly. Those 18 years and older receive 320 mg as a loading dose and 160 mg weekly thereafter. The steady-state plasma concentration is reached after 6 weeks.
3. Indications: Rilonacept is approved to treat CAPS subtypes: familial cold autoinflammatory syndrome and Muckle-Wells syndrome in patients 12 years or older. Rilonacept is also used to treat gout (see below).
Adverse Effects of Interleukin-1 Inhibitors
The most common adverse effects are injection site reactions (up to 40%) and upper respiratory tract infections. Serious infections occur rarely in patients given IL-1 inhibitors. Headache, abdominal pain, nausea, diarrhea, arthralgia, and flu-like illness all have been reported, as have hypersensitivity reactions. Patients taking IL-1 inhibitors may experience transient neutropenia, which requires regular monitoring of neutrophil counts.
Belimumab is an antibody that specifically inhibits B-lymphocyte stimulator (BLyS). It is administered as an intravenous infusion. The recommended dose is 10 mg/kg at weeks 0, 2, and 4, and every 4 weeks thereafter. Belimumab has a distribution half-life of 1.75 days and a terminal half-life of 19.4 days.
Belimumab is approved only for the treatment of adult patients with active, seropositive SLE who are receiving standard treatment. The drug was approved after a protracted series of clinical trials, and its place in the SLE armamentarium is not clear. Belimumab should not be used in patients with active renal or neurological manifestations of SLE, as there are no data for these conditions. In addition, the efficacy of belimumab has not been tested in combination with other bDMARDs or cyclophosphamide.