JIA: Not All Criteria Equal for Predicting Long-Term Outcomes

Janis C. Kelly

May 03, 2018

Long-term outcomes in juvenile idiopathic arthritis (JIA) are best predicted by clinically inactive disease as defined by the clinical Juvenile Arthritis Disease Activity score for 10 joints (cJADAS10), rather than by the Wallace preliminary criteria, researchers find.

Specialists in JIA are seeking the best target for "treat-to-target" therapy in children, more than half of whom are in remission after a decade of treatment. However, it has not been clear how to prospectively identify patients who are likely to remain in remission and those who require further treatment.

Now, British researchers have advanced that search by analyzing data for 832 children with JIA to determine which definition for clinically inactive disease (CID) after 1 year of treatment correlated best with 5-year outcomes and whether treating to CID in patients who had already reached minimal disease activity would produce further pain relief.

Stephanie J.W. Shoop-Worrall, MD, from the Arthritis Research UK Centre for Epidemiology, University of Manchester, UK, and colleagues reported in an article published online April 12 in Arthritis and Rheumatology that at 1 year after disease presentation, CID according to either set of criteria was associated with a greater absence of limited joints. However, only CID on the cJADAS10 was associated with better functional ability and psychosocial health. The researchers also found CID was better than minimal disease activity for predicting short-term and long-term pain reduction and for predicting long-term absence of joint involvement.

"The results of this analysis show that children who achieve CID at 1 year according to either measure have lower limited joint counts both at 1 year and over the next 4 years of follow-up," Shoop-Worrall and colleagues write. "However, children who achieved CID according to Wallace's preliminary criteria but not cJADAS10 were consistently found to have high levels of disability and poorer psychosocial function. Previous analysis has shown that this difference is driven by lower levels of patient wellbeing, despite the absence of active joints or other inflammatory manifestations of disease."

An important limitation of the study is that the CID definitions used have been validated only for oligoarticular and polyarticular JIA. An additional limitation is that there was no formal treat-to-target strategy in place in the United Kingdom during the study period, so although the findings suggest that early achievement of CID is associated with better outcomes, the data cannot be used to show that active treatment toward these targets produces better long-term outcomes.

How the CID Definitions Differ

The results highlight a major difference between the two definitions of CID, the authors note.

The cJADAS10 is a three-item test that includes a parent/patient assessment of well-being. The cJADAS10 criteria are:

  • physician global assessment,

  • parent/patient Visual Analogue Scale (VAS) of well-being, and

  • 10-joint active joint count.

The 5-item Wallace preliminary criteria do not include parent/patient input on well-being. The assessment is made by only the clinician, and the criteria are:

  • no active arthritis;

  • no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA;

  • no active uveitis;

  • normal erythrocyte sedimentation rate or C-reactive protein; and

  • physician's global assessment of disease activity rated at the best score possible for the instrument used.

Time to Drop the Wallace Preliminary Criteria for JIA Remission?

Two pediatric rheumatology experts not involved in the study say the results do seem to support use of the cJADAS10 criteria in the clinic.

Joost F. Swart, MD, assistant professor of Pediatric Rheumatology, UMC Utrecht, the Netherlands, told Medscape Medical News, "I read the article and indeed am convinced that the cJADAS outperforms the Wallace's preliminary criteria. We ourselves also looked at the cJADAS for treat-to-target and found that the well-being VAS of patients is crucial for its use in treat-to-target therapy. I believe that is because parents and patients do take into account all moments of the disease and not just the one at which they happen to visit the outpatient clinic. They also take into account the morning stiffness (which is not in the Wallace preliminary criteria used by Shoop-Worrall, et al), and they consider the weekend before in which the child had to stop playing during the soccer match. So all subtle hints to having a bit of disease activity are in the parent/patient well-being VAS, while the physician merely looks at the joints."

Timothy Beukelman, MD, MSCE, associate professor of pediatrics in the Division of Pediatric Rheumatology at Children's of Alabama, Birmingham, had a more cautious reaction. Beukelman told Medscape Medical News, "Although well-conducted, this study alone is insufficient to determine the most appropriate treatment target in JIA, especially because changes in treatment were not evaluated. Nevertheless, it is compelling that the 3-variable clinical JADAS10 is so easy to derive and was more strongly associated with subsequent lower disability and lower psychosocial dysfunction compared to Wallace preliminary criteria. More important to me was the finding that achievement of clinical inactive disease produced superior outcomes compared to achievement of minimal disease activity. Minimal disease activity may not be the most appropriate target, especially within the first year of disease, when few different treatment options have been attempted."

Implications for Future Research and JIA Clinical Trial Design

Swart added that this study also has implications for JIA clinical trial design. He said, "The cJADAS10 should replace the Wallace's criteria for studies and in clinical situations as well. The patients should have a voice, and the cJADAS provides one. In my opinion, we should aim at cJADAS ≤1, as stated by Consolaro, for the cJADAS. In fact, we might want to aim for that within 12 months for all of our patients."

Swart noted that the best cJADAS10 cutoff values for the in-between visits during that year still need to be validated.

Beukelman said that long-term prospective studies of different treat-to-target strategies are likely to be needed to definitively answer questions about the most appropriate JIA treatment targets.

The study authors agree that more research is needed, but emphasize the importance of the broader components in the cJADAS10 score. "The results do, however, highlight the importance of addressing all aspects of JIA and not just the underlying inflammation, in terms of best outcomes for the child."

The study was supported by the Medical Research Council and by Arthritis Research UK. The authors, Swart, and Beukelman have disclosed no relevant financial relationships.

Arthritis Rheum. Published online April 12, 2018. Abstract

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