Rituximab may be an effective treatment option for children and young people with juvenile idiopathic arthritis (JIA) who do not respond to tumor necrosis factor (TNF) inhibitors, showing a low rate of serious infections and infusion reactions, a real-world study reports.
The study, “Use and effectiveness of rituximab in children and young people with juvenile idiopathic arthritis in a cohort study in the United Kingdom,” appeared in the journal Rheumatology.
Rituximab (marketed as Rituxan in the U.S. by Genentech and as MabThera in Europe by Roche) is indicated for the treatment of adults with moderate to severe active rheumatoid arthritis who had an inadequate response to TNF blockers.
Although not approved for JIA, rituximab may be a potential treatment option for these patients, specifically for those who are refractory (non-responsive) or intolerant to TNF inhibitors. Right now, Enbrel (etanercept) and Humira (adalimumab) are the only approved and commercialized therapies for JIA in the U.S.
Rituximab’s standard regimen for arthritis requires a low number of doses compared with other biologics — two intravenous infusions given two weeks apart, with more courses considered after 24 weeks — making it an appealing treatment option for children.
But there is insufficient clinical data on its use and effectiveness for JIA.
One observational study in patients with severe and refractory JIA showed that two courses of four weekly infusions were effective, enabling 52% of patients to achieve remission of their arthritis by the 48th week.
To produce more data on the use and potential benefits of this therapy for the treatment of JIA, a team of researchers at the Arthritis Research UK Centre for Epidemiology, University of Manchester, in the U.K. conducted an observational study in 41 patients who had been exposed to rituximab treatment at some point in their lives.
All patients were registered at the Biologics for Children with Rheumatic Diseases (BCRD) — a real-world study underway at hospitals across the U.K. looking at the safety and effectiveness of biologic and biosimilar treatments for JIA.
BCRD is the U.K.’s largest study on JIA patients starting a biologic therapy other than Enbrel, likely representing most of the rituximab-treated patients in the country.
Among the 834 biologic-treated patients enrolled in the BCRD, a small percentage (5%) had been given rituximab treatment at some point. These were the 41 patients analyzed in the current study.
Most presented with polyarticular disease (35% rheumatoid factor (RF)-negative, 33% RF-positive) and extended oligoarthritis (23%). Of the patients, 80% were female, with a median age at the start of rituximab therapy of 15 years and a median disease duration of nine years.
Rituximab dosing was consistent with current guidelines for adults with rheumatoid arthritis — most patients received two 1,000 mg doses within each course. More than half received at least two courses, a median of seven months apart.
Treatment with rituximab was seen to ease disease activity, measured by several JIA core outcomes — active and limited joint count, patient-reported pain, well-being and health status, physician global assessment, clinical Juvenile Arthritis Disease Activity Score (cJADAS), and blood markers of inflammation.
Median improvement in cJADAS score from rituximab start to follow-up (three to nine months of therapy) was nine points, but this scale could only be used in seven patients.
Despite the apparent benefit of rituximab, almost half of the patients (41%) switched to another biologic therapy, including Actemra (tocilizumab), Orencia (abatacept), or a TNF blocker, over the follow-up period, suggesting that rituximab “while effective in some patients, was not considered effective in others,” according to the researchers.
The rate of serious infections was similar to those seen in previous studies with adults with rheumatoid arthritis, the researchers noted.
Three patients (7%) reported a serious infection and four (10%) an infusion reaction.
According to the researchers, “the total number of patients with polyarthritis was too small to form any conclusions” regarding differential benefits in patients who are RF-positive.
Some previous studies suggested that rituximab may be more effective in rheumatoid arthritis patients who are RF-positive, but it is still unknown if this also holds true for in JIA.
The data are “reassuring, but ultimately patients with JIA deserve a clinical trial … to establish clear efficacy and safety” of using rituximab, the researchers said.
Future studies should also investigate which JIA disease types may benefit the most from this therapy.