About one-fifth of patients with juvenile idiopathic arthritis (JIA) under age 16 are switched to second biological therapies after first-line treatments fail or cause adverse effects, a large real-world study in the U.K. has found.
The study showed no difference in disease outcomes whether patients were given a second similar biological therapy or a different class of treatment.
While the researchers recommend further studies with more patients, these findings will help inform clinical practice recommendations, treatment cost-effectiveness, and other medical policy guidelines.
The study, “Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study,” was published in the journal The Lancet Rheumatology.
Biological disease-modifying antirheumatic drugs (DMARDs), or biologics, are a standard treatment option for people with JIA, particularly for those who are intolerant or do not respond to conventional (synthetic) DMARDs, such as methotrexate.
More recently, other classes of biologics have become available, and include therapies such as Orencia (abatacept, by Bristol-Myers Squibb), Actemra (tocilizumab, by Genentech), Kineret (anakinra, by Sobi), and Ilaris (canakinumab, by Novartis).
Some JIA patients switch from one biologic to another until their disease is under control. However, little information is available to help determine the most effective second-line biological therapy, which is reflected in different recommendations by NHS England and the American College of Rheumatology (ACR).
To investigate the best choices for second-line biologics when first-line options fail, researchers at The University of Manchester in the U.K. assessed the proportion of JIA patients younger than 16 who had switched to a second biologic therapy. The scientists also studied the extent of multiple switches, patterns of switching, and the effectiveness of different classes of biologics after switching from a first-line TNF inhibitor.
This analysis included JIA patients who were enrolled in one of two U.K. studies: the Biologics for Children with Rheumatic Diseases study and the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study.
The assessment was conducted in two parts: switching patterns in all children who started their first biologic from Jan 1, 2010, and response to a second biologic in those starting their first biologic from Jan 1, 2004.
Among the 1,152 JIA patients (97 of whom had systemic JIA) who started their first biological treatment in 2010, 1,055 (91%) patients were first prescribed a TNF inhibitor. Of the 1,132 patients with available data, 1,081 (95%) were first treated with methotrexate before the biological therapy.
During a median follow-up duration per patient of 2.2 years, 270 (23%) were prescribed a second biologic, 61 (5%) started a third biologic, and 11 (1%) were treated with a fourth biological therapy. Of the 270 that were given a second biologic, 163 (60%) switched due to ineffectiveness of the first-line treatment, and 66 (24%) switched due to adverse events. Switching to a third and fourth biologic was also due to treatment failure or adverse events.
“For many children and young people with juvenile idiopathic arthritis, treatment with a first or second biologic is not beneficial,” the investigators wrote.
Analysis of the second part of the study found that 2,361 patients were given a biologic therapy since 2004. Of them, 817 (35%) switched to a second biologic, which included 282 (35%) patients with polyarticular JIA.
The assessment of response was carried out in 240 of these 282 patients. A total of 194 (81%) started a second TNF inhibitor, and 46 (19%) started an alternative class of biological therapy — with 33 prescribed Actemra, six given Orencia, six treated with rituximab (marketed as Rituxan and MabThera), and one given off-label Stelara (ustekinumab, by Janssen Biotech).
At six months of follow-up, no differences in disease activity — assessed with the Juvenile Arthritis Disease Activity Score (JADAS-71) — were seen between patients given a second TNF inhibitor and those prescribed an alternative class of biological therapy.
Likewise, no differences were found between these groups in the proportion of patients with polyarticular JIA who achieved minimal disease activity or ACR Pedi 90 response, which is the proportion of patients who achieve at least 90% improvement in at least three of six variables. These variables assess disease activity, overall well-being, functional ability, number of joints with active arthritis, number of joints with limited range-of-motion, and inflammation.
“Our results showed that biologic switching is not uncommon, with more than one-fifth of patients starting a second biologic,” the scientists wrote. “The response to a second biologic was similar between patients who switched to a biologic of the same class and those who switched to a biologic of a different class.”
“Repeat analysis with a larger sample size is required to validate these findings,” they added.
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