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Tocilizumab might be a useful adjunctive therapeutic option for children with juvenile idiopathic arthritis-associated uveitis that doesn't respond to TNFi treatment, say researchers recently writing in The Lancet Rheumatology.
Tocilizumab (Actemra, Genentech) might be a useful adjunctive therapeutic option for children with juvenile idiopathic arthritis-associated uveitis refractory to anti-tumor necrosis factor (TNF) treatments, say researchers recently writing in The Lancet Rheumatology.
Juvenile idiopathic arthritis affects one in 1,000 children and up to 80 percent of all cases of pediatric uveitis are secondary to the condition. Children with moderate to severe uveitis can be refractory to both methotrexate and TNF inhibitors and are therefore at great risk of ocular complications and blindness. Tocilizumab, an interleukin-6-receptor inhibitor, is approved for use in systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis. However, patients with juvenile idiopathic arthritis-associated uveitis have been excluded in clinical trials, so the efficacy of tocilizumab in these patients is unclear.
“Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors,” wrote the authors, led by Athimalaipet V Ramanan, F.R.C.P., of the University of Bristol in the U.K.
The phase II APTITUDE trial included 21 patients aged five to 18 years with active juvenile idiopathic arthritis-associated uveitis. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to TNF inhibitor treatment. Patients received subcutaneous tocilizumab every two to three weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the inflammation level (anterior chamber cells) at week 12, per the standardization of uveitis nomenclature criteria.
The primary endpoint was not met. Seven of the 21 participants (median unbiased estimate of proportion 34 percent [95% CI 25–57]) responded to treatment (p=0·11). Safety results were consistent with the known safety profile of tocilizumab.
“To our knowledge, this is first trial looking at efficacy of tocilizumab in juvenile idiopathic arthritis-associated uveitis.
“Despite this trial not meeting the threshold required to justify a larger phase III trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options,” the authors wrote.
“This study is able to give early indications of the potential clinical effectiveness of tocilizumab in combination with methotrexate for the treatment of children with refractory juvenile idiopathic arthritis-associated uveitis,” the authors wrote. “This study also provides evidence of efficacy in macular edema associated with juvenile idiopathic arthritis uveitis, as reported in previous studies.”
Athimalaipet V Ramanan, Andrew D Dick, Catherine Guly, et al. “Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial.” The Lancet Rheumatology. February 7, 2020. DOI:https://doi.org/10.1016/S2665-9913(20)30008-4