Long-term treatment with Humira (adalimumab) — reaching through six years — was well-tolerated and effective in children with polyarticular juvenile idiopathic arthritis (JIA), a Phase 3 trial with an extension study found.
Results showed that 37% of patients achieved clinical remission, and most had low disease activity for the duration of the study.
The study, “Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate,” was published in the journal RMD Open.
Children with JIA are initially treated with non-steroidal anti-inflammatory drugs (NSAIDs) or methotrexate, a prescription medication with anti-inflammatory properties.
In more severe cases of JIA, biologics — medications that are derived from living organisms — are prescribed. Several biologics are available for arthritic conditions, because patients respond differently to the different treatments, both in terms of benefits realized and adverse reactions.
Humira, marketed by AbbVie, is a biologic designed to suppress the immune system activity in people with chronic conditions, including arthritis, inflammatory bowel disease, ankylosing spondylitis, and more.
A Phase 3 clinical trial (NCT00048542) evaluated Humira in children with polyarticular JIA who did not respond to NSAIDs, and may or may not have been using methotrexate (those using it were allowed to continue). The study was sponsored by Abbott; AbbVie is a spinoff of that company.
The trial began with a 16-week open-label period, in which all enrolled children were given Humira. Participants with a 30% or greater clinical improvement on Humira, as evaluated by the Juvenile Idiopathic Arthritis – American College of Rheumatology (JIA ACR) guidelines, were eligible to move into its second period: a 32-week, double-blind trial with patients randomly assigned to either Humira or a placebo.
During these periods, Humira was given every other week via subcutaneous (under the skin) injection, at a dose of 24 mg/m2 (per square meter of body surface area), with a maximum dosage of 40 mg.
Patients who completed the 48-week course were eligible for a two-part, long-term extension, in which all received the same dose of Humira for an additional 44 to 136 weeks (2.6 years), followed by a fixed dosage period for up to 224 weeks (4.3 years). Dosage here was fixed at either 20 mg for patients weighing less than 30 kg (about 66 lbs) or 40 mg for participants weighing more.
Of the 171 children, ages 4 to 17 (average age, 11.3) first enrolled in the study, 62 (36%) completed the full course of the extension; 125 finished the double-blind period.
A total of 3,605 adverse events and 75 serious adverse events were reported, and 19 serious side effects were deemed possibly related to the treatment.
The most common adverse events were injection site reactions (912) and infections (880), 12 of which in 11 patients were considered serious. Seven such infections were attributed to Humira. No patients died during the study.
At two years of treatment, 90 of 94 evaluated patients achieved a 30% clinical improvement, 88 reached 50%, 84 achieved 70%, and 62 had a 90% improvement, as evaluated under the JIA ACR guidelines. Response rates were maintained during the extension phase, regardless of dose changes.
The 27-item Juvenile Arthritis Disease Activity Score (JADAS27) system, which categorizes greater disease severity by increasing scores, was also used to evaluate Humira’s efficacy.
Based on JADAS27 scores, the researchers found that 73% of patients had low disease activity after two years, and that 43% had inactive disease. Scores were maintained over the full six years.
Clinical remission was reached by 37% of these children, as their inactive disease scores held over six months. The median time to reach remission was 216 weeks, or 4.2 years.
Results showed a significant improvement in JADAS27 scores over the study’s entire course, lowering from 22.5 at baseline (study start) to 2.5 at six years.
“The results of this study show that long-term adalimumab [Humira] therapy is well tolerated and effective in patients with polyarticular JIA,” the researchers wrote, adding that this study’s “low treatment retention rate should be noted when assessing these results.”
“Overall, our results support the use of adalimumab as a therapy option for patients with active polyarticular JIA,” they added.