Review of Biologics in Children With Rheumatic Diseases

Shabina Habibi; Athimalaipet V Ramanan


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

In This Article

Inhibition of T-cell Costimulation


Abatacept is a fully human soluble fusion protein that contains the Fc portion of IgG1 linked to CTLA-4. It binds to CD80 or CD86, and inhibits T-cell activation. It has been studied in children with polyarticular course of JIA, including some who were refractory to other biologics.[51] The trial design was again similar to the etanercept trial. One hundred and ninety children were enrolled, among which one third were refractory to anti-TNF-α therapy. They were treated with 10 mg/kg of abatacept, given every 4 weeks, with or without methotrexate. Two-thirds achieved ACR-Pedi 30 response during the open-label lead in phase. Significantly more children who had not received anti-TNF-α therapy responded, as compared with those who had previously received anti-TNF-α therapy (76 vs 39%). During the double-blind, placebo-controlled phase, 53% of children on placebo flared, as compared with 20% receiving abatacept, with median time to flare being shorter in those on placebo. ACR-Pedi 30, 50, 70 and 90 responses in the abatacept and placebo group were 82, 77, 53 and 40% versus 69, 52, 39 and 16%, respectively. Few serious adverse events were reported.

One hundred and fifty three children entered the long-term extension open-label phase.[52] Among those who received abatacept in both the double-blind and open-label extension phase, 90, 88, 75, 57 and 39% attained ACR-Pedi 30, 50, 70, 90 and 100 responses, respectively. Responses were either maintained or progressively improved. Response rates were similar among those who had received biologics prior to abatacept to those who had not. Clinical responses were also similar in those children who were randomized to receive placebo in the double-blind phase, suggesting that interruption of the drug for as long as 6 months is well tolerated. The safety profile was found to be favorable. A total of 73% of the children who did not attain ACR-Pedi 30 response at the end of the open-label lead-in phase, and thus were not randomized, attained this response during the open-label long-term extension phase. This suggests that responses in some children may be delayed.

A case series of seven children with JIA-associated uveitis, refractory to immunosuppressants and ≥2 anti-TNF-α agents reported the efficacy of abatacept in the treating the uveitis and maintaining its remission for a mean of 9 months.[53] The mean frequency of uveitis flares was also decreased.

Abatacept was FDA approved in 2008 for the treatment of moderate-to-severe polyarticular JIA, in children more than 6 years old. It is administered as an intravenous infusion over 30 min, at a dose of 10 mg/kg, up to a maximum of 1000 mg at 0, 2 and 4 weeks, and then every 4 weeks.


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