The Food and Drug Administration's recent approval of the tumor necrosis factor blocker adalimumab for treating juvenile idiopathic arthritis makes it the first biologic treatment approved for this indication since the 1999 approval of the TNF-blocker etanercept.
Adalimumab was approved for reducing the signs and symptoms of moderately to severely active juvenile idiopathic arthritis (JIA) in patients aged 4 years and older, alone or in combination with methotrexate. It is administered by a subcutaneous injection every other week, at doses based on weight.
Adalimumab is “an excellent choice for children with severe arthritis who need an anti-TNF agent,” Dr. Thomas Lehman, chief of the division of pediatric rheumatology, at the Hospital for Special Surgery, New York City, said in an interview. Although many children are initially controlled on etanercept, “those who break through often respond to Humira [adalimumab], as do most of those who do not respond to Enbrel [etanercept] initially,” he said.
Dr. Lehman said that adalimumab has been used extensively in pediatric patients over the past 4 years. “We've had excellent success in children with severe arthritis or uveitis associated with juvenile arthritis who have not responded to Enbrel,” he said. Dr. Lehman said he was not involved in the study that led to approval, but is a speaker for Abbott Laboratories, which markets adalimumab as Humira, and etanercept (Enbrel) manufacturer Amgen.
Approval was based on a four-phase, multicenter study of 171 children, aged 4–17 years with polyarticular JIA, with signs of active moderate or severe disease, despite previous treatment with NSAIDs, analgesics, corticosteroids, or disease-modifying antirheumatic drugs. (Patients who had been treated with biologic therapies before were excluded.) During the first phase, all patients received adalimumab for 16 weeks; 94% of those on methotrexate and 74% of those not on methotrexate had a pediatric American College of Rheumatology 30 response. These responders were randomized to continue to receive treatment or were switched to placebo; at the end of 32 weeks, significantly fewer of those who remained on adalimumab had disease flares, compared with those who were switched to placebo: Among those on methotrexate, 37% of those on adalimumab had a flare vs. 65% of those on placebo. Among those not on methotrexate, 43% of those on adalimumab had a flare vs. 71% of those on placebo.
ACR responses were maintained for up to 2 years among those who continued with treatment during the open-label extension phase of the study.
Overall, the type and frequency of adverse reactions were similar in the pediatric patients to those seen in adults. Neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis were among the severe adverse reactions reported in the JIA study, according to Abbott. The labels for adalimumab and the other TNF blockers carry a black box warning about the risk of serious infections associated with treatment. In the JIA study, 4% of patients had a serious infection within about 2 years of starting treatment, and included herpes simplex, pneumonia, urinary tract infections, pharyngitis, and herpes zoster, according to Abbott.