Drugs Xagena
European Commission ( EC ) has approved the use of Ilaris ( Canakinumab ) in the treatment of active systemic juvenile idiopathic arthritis ( SJIA ) in patients aged 2 years and older, who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs ( NSAIDs ) and systemic corticosteroids.
Systemic juvenile idiopathic arthritis is a rare and disabling form of childhood arthritis with limited treatment options. The condition is characterized by spiking fever, rash and arthritis that can affect children as young as 2 years old and can continue into adulthood. Ilaris can be given as monotherapy or in combination with Methotrexate.
This approval was based on two phase III trials in systemic juvenile idiopathic arthritis patients, aged 2-19, which showed significant improvement in the majority of Ilaris-treated patients.
Study 1 showed that 84% of patients treated with one subcutaneous dose of Ilaris achieved the primary endpoint of the adapted pediatric American College of Rheumatology 30 ( ACR30 ), compared to 10% achievement of ACR30 for placebo at day 15.
In the open-label part of Study 2, 92 of 128 patients attempted corticosteroid tapering. Of those 92 patients, 62% were able to substantially reduce their use of corticosteroids, and 46% completely discontinued corticosteroids. In the controlled portion of Study 2, there was a 64% relative reduction in the risk of flare for patients in the Ilaris group as compared to those in the placebo group ( hazard ratio, HR=0.36 ).
Data from a pooled efficacy analysis showed that after 12 weeks of Ilaris treatment 61% of patients reached an adapted pediatric ACR70 and 28% of patients had inactive disease.
The incidence of systemic juvenile idiopathic arthritis in Europe is thought to be around 0.4-0.8 per 100,000, with a prevalence estimated at 1-10 in 30,000 children.
Although the disease can be life-threatening, treatment options are limited. Corticosteroids are often used to treat symptoms and pain despite their long-term use being associated with potentially serious adverse effects, including Cushing syndrome, growth suppression and osteoporosis.
Study 1, a 4-week, randomized, double-blind, placebo-controlled study, involved 84 patients between the ages of 2 and 19 years with active SJIA. Patients were treated with either a single subcutaneous dose of Ilaris ( 4 mg/kg, up to 300 mg ) ( n=43 ) or placebo ( n=41 ). The primary endpoint was the proportion of patients achieving the adapted pediatric ACR30 response criteria and resolution of fever from baseline at day 15. This means that patients had at least a 30% improvement in systemic and arthritic symptoms versus baseline. The study met its primary endpoint.
Study 2, a two-part study, had an open-label, single-arm active treatment in part I followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design in part II. A total of 177 patients between the ages of 2 and 19 years with active systemic juvenile idiopathic arthritis were enrolled in the study. Some of these patients had previously participated in the Study 1. In Part I, patients received a subcutaneous dose of Ilaris ( 4 mg/kg, up to 300 mg ) every 4 weeks. The primary endpoint of Part I was to assess whether treatment with Ilaris allowed successful tapering of corticosteroids in at least 25% of systemic juvenile idiopathic arthritis patients who entered the study using a corticosteroid.
In Part II of the study, patients were randomized to either continue receiving Ilaris, or to receive placebo every 4 weeks ( placebo-after-Canakinumab group ), until a pre-specified number ( 37 ) of flare-events ( flares ) had occurred. The primary endpoint of Part II was to demonstrate that the time to flare was longer with Ilaris than with placebo.
Ilaris is a selective, fully human, monoclonal antibody that inhibits IL-1 beta, which is an important part of the body's immune system defenses. Excessive production of IL-1 beta plays a prominent role in certain inflammatory diseases. Ilaris works by neutralizing IL-1 beta for a sustained period of time, therefore inhibiting inflammation. ( Xagena )
Source: Novartis, 2013
XagenaMedicine_2013
