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The aim of this study: to determine which patients need biologic therapy after starting methotrexate.
The clinical Juvenile Arthritis Disease Activity Score (cJADAS) can be used for treat-to-target therapy in juvenile idiopathic arthritis (JIA), according to new research
JIA is the most common chronic rheumatic disease in children. Over the past 10 years, the development of biologic medications, such as anti-tumor necrosis factor (anti-TNF) therapy, has led to dramatic improvements in the treatment of JIA. However, it is not yet fully established which patients need biologics or exactly when to start them.
While the American College of Rheumatology has issued clinical practice guidelines (ACR-CPG) for the treatment of JIA, physicians do not always follow these guidelines when making actual treatment decisions. The Juvenile Arthritis Disease Activity Score (JADAS) was recently developed to create better consistency in disease activity evaluation across physicians. It is constructed around four elements: the active joint count (AJC); physician global assessment (PGA); parent/patient Visual Analogue Scale (VAS) of well-being; and the erythrocyte sedimentation rate (ESR). The cJADAS is a three-element variant that does not require waiting for the ESR results.
Led by Joost F. Swart of the Department of Pediatric Rheumatology and Immunology at the Wilhelmina Children’s Hospital in Utrecht, Netherlands, and published in Annals of the Rheumatic Diseases, this study looked at whether the JADAS or the cJADAS could be used to identify patients with JIA in need of anti-TNF therapy at 3 and 6 months after starting methotrexate.1
This monocentric retrospective cohort study included patients from April 2011 to December 2015 with two subtypes of JIA: oligoarticular JIA (OJIA) and polyarticular course JIA (PJIA). These patients had all started methotrexate for the first time, were biologic naive, were aged zero to 18 years at the start of medication, and were followed for at least 12 months after the start of treatment. Data included 145 patients, with 15 in the OJIA group and 17 in the PJIA group excluded for various reasons.
For OJIA, the ACR-CPG recommended escalation to anti-TNF in 18% of patients at 3 months, but only 8% were actually escalated by the physician. At 6 months, the ACR-CPG recommended only one patient to escalate, but the physician actually escalated 11% (n = 4) patients. The correct identification of patients in need of anti-TNF (sensitivity) of the ACR-CPG was low at 3 and 6 months (10% and 0% of non-responders were recommended to escalate, respectively). The correct recommendation not to escalate (specificity) was high (86% and 95% of responders not recommended to escalate)
For PJIA, the ACR-CPG recommended escalation to anti-TNF in 59% of patients at 3 months, but therapy was escalated in only 18%. At 6 months, the ACR-CPG recommended that 70% of patients be escalated, and the physician actually escalated 13%. In contrast to OJIA, for PJIA at 3 and 6 months, the sensitivity of the ACR-CPG was high (87% and 78%) and the specificity was low (44% and 29%).
When considering the performance of the JADAS and cJADAS, the cJADAS had better accuracy and higher sensitivity, specificity, and sum scores. In predicting the failure on methotrexate, and thus the need to escalate to anti-TNF therapy, the cut-off values for cJADAS that best performed were > 5 for OJIA and > 7 for PJIA at 3 months. At 6 months, the best cut-off values were > 3 for OJIA and > 4 for PJIA. The researchers found there was no considerable benefit of including the ESR.
Implications for physicians
Overall, the ACR-CPG recommended escalation to anti-TNF therapy in 65% of all time points, but the physicians only escalated 12% of the time. As the decision not to escalate was correct in 70% to 75% of the cases, the researchers observed that the ACR-CPG “seems to result in overtreatment with anti-TNF, even in some patients that are regarded as inactive by their physicians at that exact moment.”
Alternatively, the researchers showed that the cJADAS could be used in clinical practice to predict treatment failure at 12 months after the start of methotrexate. “The cJADAS incorporates the patient perspective, is very user-friendly, and does not need waiting for the ESR results before a decision can be made,” the researchers concluded. “We therefore believe that the cJADAS can be used for treat-to-target therapy in JIA.”
Since this study was a single-center experience with a rather small number of patients, the researchers recommend larger multi-center studies to validate these findings and optimize the cut-off values. In large prospective studies, the predictive value of multiple biomarkers should also be explored.
This study was supported by Pfizer and by the Dutch Arthritis Foundation.
1. Swart JF, van Dijkhuizen EHP, Wulffraat NM, de Roock S. Clinical Juvenile Arthritis Disease Activity Score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann Rheum Dis. 2017 Nov 14. pii: annrheumdis-2017-212104. doi: 10.1136/annrheumdis-2017-212104. [Epub ahead of print]