This small retrospective study of children with refractory uveitis found that the addition of a third immunosuppressive agent did not confer substantial benefit in redressing ocular inflammation and was associated with significant infections in a minority of patients.
The authors examined the results of 13 patients aged 16 and younger with bilateral refractory chronic noninfectious uveitis who were treated with triple immunosuppressive therapy for at least six months. Eleven patients had juvenile idiopathic arthritis, one had Blau syndrome and one had idiopathic uveitis.
All 13 children had persistent uveitis on two agents (in addition to corticosteroids). Triple therapy was a combination of three of the following: methotrexate, mycophenolate, a tumor necrosis inhibitor or tacrolimus.
Six months after starting triple therapy, ocular inflammation had improved in 42 percent of the eyes. Nevertheless, two-thirds of eyes continued to have active iritis and two-thirds still required corticosteroid drops. While some patients could stop or decrease their use of corticosteroids on triple therapy, with 58 percent using a tapered dose, three patients required an increased dose of corticosteroids.
There were 16 adverse events, with four being significant as the patients were hospitalized. One patient had chickenpox, one had H1N1 swine flu and another had two episodes of pneumonia, for a rate of serious adverse reactions of 0.18 per patient-year (the rate for the three patients was 0.14 per patient-year).
Some patients clearly had a beneficial response to triple therapy, and this may be helpful in select cases, say, before surgery, but the authors suggest that the risks of triple therapy treatment outweigh the benefits. They say that early intervention with first-line and second-line immunosuppressive agents may be more beneficial than attempts at late triple therapy rescue for established refractory disease.
Of course few patients have such refractory uveitis, but when they do, it is difficult to know what to do. Possibilities include using other medications, such as alkylating agents, newer biologics, or biologics with which we have less experience in uveitis, such as rituximab. The jury is still out and we have to take each case as it comes, but clearly more is not always better.