A 20-month-old girl was admitted with a prolonged febrile syndrome of 5 months' duration, intermittent in the first months and constant in the following 2 months, with a maximum temperature of less than 39°C and intermittent in the last two months. The patient presented with maculopapuloerythematous, evanescent exanthema on the trunk and proximal extremities, lymphadenopathy since the age of 13 months, affecting the cervical, axillary and inguinal nodes, and hepatomegaly. Laboratory tests showed anaemia (9.3 g/dL), leukocytosis (27,340/mm3) and increased ESR. The clinical and laboratory manifestations were suggestive of JIA, and treatment was started with oral prednisone at 2 mg/kg/day (10 mg every 12 hours). After one month, the dose was reduced and an interleukin 1 receptor antagonist (Anakinra) was added at 1 mg/kg/day subcutaneously.
After 2 weeks of treatment, the patient developed hypertransaminemia of probable viral aetiology, and the anakinra was withdrawn, causing a clinical worsening with recurrence of skin lesions, arthralgias and fever, requiring high doses of corticosteroids to control the disease, and the Hospital's Pharmacy and Therapeutics Committee (CFT) was asked to approve the off-label use of canakinumab.
Canakinumab is a fully human monoclonal antibody that binds with high affinity to human interleukin-1 beta, neutralising its biological activity4. At the time of application canakinumab was indicated for the treatment of Cryopyrin Associated Periodic Syndromes (CAPS) in adults, adolescents and children aged 2 years and older, but a recently published study5 is available with results of this drug in JIA in children over 4 years administered at 4mg/kg subcutaneously every 4 weeks. The PTC agrees to approve it and treatment is started at 2mg/kg every 4 weeks to test tolerance. Given the patient's weight, the Pharmacy Service reformulated the vial to allow for multiple doses and to be more efficient.
Adequate tolerance and good response to the biologic was observed at a dose of 2 mg/kg/4 weeks, with symptoms disappearing, which allowed the corticosteroid dose to be reduced to 8 mg/day, and the patient continued to progress well. The dose of canakinumab was increased to 3 mg/kg/4 weeks and the corticosteroid was withdrawn until discontinuation.
After 6 months of treatment, she suffered a new relapse with sustained febrile fever, irritability and some skin lesions, so the dose of canakinumab was increased to the optimal dose of 4 mg/kg/4 weeks, reintroducing corticosteroids. The disease remained stable despite an infectious process that subsided without secondary complications, during which time the biologic was discontinued.
After 7 months of treatment, methotrexate 7.5 mg/week subcutaneous was added together with calcium folinate, 7 mg/week, due to the development of joint manifestations in elbows and carpals that appeared painful and inflamed. Eight weeks later, the patient developed coagulation disorders and hypertrasaminemia, probably secondary to methotrexate treatment, and monocytosis, which led to her admission and discontinuation of methotrexate and canakinumab. During admission, the patient progressed favourably and was diagnosed with active polyarticular JIA, so it was decided to start etanercept 0.4 mg/kg/week subcutaneously to treat the joint manifestations. Although the clinical response to the new biologic was satisfactory, its administration was suspended for 15 days due to a new elevation of transaminases until its resolution. two months later, the patient was admitted for arthrocentesis in both knees. From then on, the patient continued treatment with etanercept 0.4mg/week, continuing to improve without skin lesions or fever and allowing corticosteroids to be reduced to 4 mg/day.

