Adding Humira (adalimumab) to methotrexate lowers the risk of juvenile idiopathic arthritis-associated uveitis flares and helps to maintain visual acuity in children who do not respond to methotrexate alone, a study found. These benefits do not persist after stopping Humira, but its researchers saw the possibility of a “continued role” for the treatment in children with this disease.
The study “Adalimumab in juvenile-idiopathic arthritis-associated uveitis (JIA-U): 5-year follow-up of the Bristol participants of the SYCAMORE trial,” was published in the American Journal of Ophthalmology.
Uveitis is an inflammatory condition that causes swelling and destruction of ocular tissues mainly in a part of the eye called uvea. Juvenile idiopathic arthritis-associated uveitis (JIA-U) is detected in 13% to 24% of JIA patients within seven years of diagnosis, and is the main cause of uveitis in children and young adults.
JIA-associated uveitis treatment has relied on local steroids or corticosteroids that reduce inflammation. However, this treatment is highly linked to the development of cataracts and glaucoma — a condition that causes damage to the eye’s optic nerve.
Current recommendations suggest JIA-U should be treated early with methotrexate, a type of disease-modifying anti-rheumatic drug (DMARD) that lowers the activity of the immune system, tuning down inflammation. But some patients experience intolerable side effects to methotrexate, and the treatment does not always fully control uveitis.
Recently, AbbVie’s Humira (adalimumab), an antibody that works by blocking the action of a cytokine called the tumor necrosis factor (TNF), was approved for treatment of JIA-associated uveitis in Europe. The approval was based on the positive results of the SYCAMORE (2010-021141-41) trial in the U.K.
The trial evaluated the efficacy and safety of Humira in 90 children and adolescents (ages 2 or older) with active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned to either Humira (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously (into the skin) every two weeks. Patients received the therapy until treatment failure or until 18 months elapsed.
Adding Humira to methotrexate significantly delayed the time to treatment failure compared with placebo. Treatment failure occurred in a significantly lower percentage of patients in the Humira group compared to methotrexate alone, 27% vs. 60%, respectively.
Now, researchers performed a retrospective long-term study of 28 SYCAMORE trial participants, mean age 10.25 and mainly (72%) females. After the trial, patients were followed for a median of four years.
Nineteen of these patients had been randomized to the Humira and nine to the placebo group. All were treated with methotrexate during trial.
Twenty-six of the 28 participants had a flare of JIA-associated uveitis after SYCAMORE ended. Of the 12 children who completed the Humira arm of the trial, 92% (11) had a uveitis flare during the extended study follow-up period after stopping Humira. The median time to a flare was 188 days.
Only one placebo group participant completed the trial. Time-to-flare for this group was 511 days, and seven (78%) of the nine placebo participants were then treated with Humira following an uveitis flare.
A total of 27 participants did not show a sustained loss of visual acuity during follow-up. Cataracts developed in 14% of them, and 11% had ocular hypertension with eye pressure above 25 millimeters Hg. The most common adverse effect was minor infections. Overall, there were a total of 30 adverse events in 10 patients during follow-up.
“For the majority of children, drug-induced remission of JIA-U did not persist when [Humira] was withdrawn after 1-2 years of treatment on the trial,” the researchers wrote, adding that “eleven (92%) of the participants on the active treatment arm who completed the SYCAMORE trial were subsequently restarted on adalimumab because of relapse of uveitis.”
These results support the need for a “continued role for [Humira] in JIA-U, but not without safety and cost considerations,” they added. “The method of withdrawing [Humira] requires further exploration, as participants who stopped adalimumab did so suddenly, and the optimal duration of treatment also remains unclear.”
Researchers noted that this particular group of patients were resistant to at least 12 weeks of methotrexate treatment, and were treated with both Humira and methotrexate for a long period. As a result, they advert caution since these observations may not be applicable to mild or moderate forms of JIA-associated uveitis.
Humira was approved by the U.S. Food and Drug Administration to treat polyarticular JIA, or disease-related joint inflammation, in 2008.