Three-Item Juvenile Arthritis Scale Can Guide Anti-TNF Use

Janis C. Kelly

November 30, 2017

A simple modification of the Juvenile Arthritis Disease Activity Score (JADAS) that could be used in routine clinical practice may simplify treat-to-target care for juvenile patients with oligoarticular (OJIA) or polyarticular (PJIA) juvenile idiopathic arthritis, Joost F. Swart, MD, and colleagues report in an article published in the Annals of the Rheumatic Diseases. This tool might help clinicians navigate the complex path between undertreatment of patients with JIA whose underlying disease will not be sufficiently controlled by methotrexate (MTX) by 12 months and unnecessary early use of expensive biologicals in patients whose disease can be expected to respond to MTX.

The clinical JADAS (cJADAS) uses the physician global assessment, the parent/patient Visual Analogue Scale (VAS) of well-being, and the active joint count to calculate a disease activity score. It differs from the full JADAS in omitting erythrocyte sedimentation rate.

"Our key finding was that the three-item cJADAS (without the [erythrocyte sedimentation rate]) could be used to identify JIA patients who should be escalated to anti-TNF therapy after 3 months or 6 months of MTX. Clinicians could be using the cJADAS as guide for treatment; however, the optimal cut-off values for the escalation to anti-TNF need to be validated in a new cohort. This will take place soon. We already display cJADAS graphs in our clinical practice, and patients love it (as do we)," lead author Joost F. Swart, MD, told Medscape Medical News. Dr Swart is pediatric rheumatologist/immunologist, Department of Pediatric Immunology and Rheumatology, UMC Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands.

The cJADAS score, as defined for JIA by Consolaro et al, combines the physician global assessment of overall disease activity measured on a 0 to 10 VAS, where 0 = no activity and 10 = maximum activity; parent/child ratings of well-being assessed on a 0 to 10 VAS, where 0 = best and 10 = worst; and the active joint count assessed in 71, 27, or 10 joints (cJADAS71, cJADAS27, or cJADAS10). The cJADAS in the Swart study used the active joint count 71-joint count, which yielded a global score of 0 to 91.

The single-center, retrospective cohort study included 39 patients with OJIA and 74 patients with PJIA, all of whom were first starting MTX. Dr Swart pointed out that the study did not include two of the seven JIA subtypes: JIA with enthesitis and systemic JIA.

At 3 and 6 months after MTX start, patients were assessed using the 2011 American College of Rheumatology (ACR) JIA clinical practice guideline, the full JADAS71, and the cJADAS. This comparison was made in part because the clinical practice guideline has not gained wide acceptance, apparently as a result of its complexity for use in daily practice, and the JADAS71 and cJADAS were being tested as possible replacements.

The researchers report, "The cJADAS incorporates the patient perspective, is very user-friendly and does not need waiting for [erythrocyte sedimentation rate] results before a decision can be made. We therefore believe that the cJADAS can be used for treat-to-target therapy in JIA. The cut-off values for cJADAS that we found for the need to escalate to anti-TNF were >5 for OJIA and >7 for PJIA at 3 months and >3 for OJIA and >4 for PJIA at 6 months."

"In fact, we wondered what the real decisive reasons were for physicians to escalate to anti-TNF or not, but this was not clear-cut. We expected that we were likely to follow the ACR 2011 recommendations for JIA, but this was not the case at all, and would totally change our practice today if we would do so," Dr Swart told Medscape Medical News.

"We looked for the best way to improve these really important decisions and make them more transparent. This was the reason we chose to look at the composite score of cJADAS as an instrument/tool to predict nonresponse to MTX, and therefore the need to escalate to anti-TNF. We felt that 3 months of nonresponse is different from 6 months of nonresponse. This difference was relevant for the choice of cut-off values: We felt that the risk of overtreatment at 3 months is higher, and we really wished to avoid undertreating, [which is why the cut-off scores are lower at 6 months,]" Dr Swart explained.

He said that he had been "honestly surprised" to discover that the ACR JIA clinical practice guideline was not easy to understand and not really helpful in identifying patients in need of anti-TNF. "I was pleasantly surprised that the cJADAS was able to discriminate in this. I also had not expected...the "voice" of the patient [the parent/patient VAS] to be so critical in this."

Timothy Beukelman, MD, MSCE, from the Division of Pediatric Rheumatology, University of Alabama at Birmingham, who was lead author for the 2011 ACR Recommendations for the Treatment of JIA, told Medscape Medical News the recommendations were not developed to predict which patients would require initiation of anti-TNF inhibitor therapy to achieve inactive disease 12 months after initiation of methotrexate, the question asked in the current study.

"Nevertheless, this fact does not detract from this important and impactful study that highlights the potential utility of cJADAS for a treat-to-target approach in JIA," Dr Beukelman said. He explained that at the time when the 2011 ACR Recommendations were being developed, the JADAS was relatively new and still undergoing validation. "The simplicity of the cJADAS is very appealing, making studies that examine its performance in clinical practice very important," Dr Beukelman explained.

However, Dr Beukelman disagreed with some of the authors' concerns about potential "overtreatment" of JIA with anti-TNF therapy.

Dr Beukelman said, "The issues with the ACR recommendations aside, I think that 'over-treatment' is not easily defined. Achievement of clinical inactive disease at a single arbitrary time-point is not sufficient to assess treatment success. For that we need longer-term outcomes. If the outcome definition used in this study is accepted, then 30% of the patients who did not receive TNF inhibitors were 'undertreated' by their physicians because they had persistent disease activity. To me, this is far more worrisome than 'overtreatment.' "

Dr Swart's group currently measures cJADAS for every patient with JIA at each visit, but does not yet use it to guide decisions on anti-TNV therapy, as the cut-off values need to be validated. "The obvious question is, How will cJADAS perform in a new cohort? I believe that soon we will be able to sit down with, for example, a PJIA patient and tell them that we start MTX today, but if 3 months from now the cJADAS is still >7 (if validated in another cohort), we will need to change therapy, or if after 6 months the cJADAS is >4, we will also change. At this moment, only the sequence of the drugs [for treat-to-target therapy] is agreed upon, not the target you and the patient are aiming at for a certain point in time," Dr Swart said.

The study was supported by Pfizer and by the Dutch Arthritis Foundation (Reumafonds). The authors and Dr Beukelman have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online November 14, 2017. Full text

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