Treatment Targets in JIA: Comparing Definitions of Clinically Inactive Disease

Treat-to-target strategies in juvenile idiopathic arthritis (JIA) may benefit more, in terms of long-term outcomes and ease of application, from focusing on clinically inactive disease (CID) rather than minimal disease activity (MDA) as a target, according to research published in Arthritis & Rheumatology. In addition, CID on the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) may be a preferable target vs CID defined by Wallace’s preliminary criteria.

Treat-to-target strategies have been successful in adult rheumatology, but the best target for patients with JIA remains uncertain, especially regarding long-term outcomes. CID and MDA have both been suggested as potential ideal targets in this endeavor. The investigators aimed to examine the utility of these targets in terms of joint limitations, functional ability, psychosocial health, and pain levels.

The Childhood Arthritis Prospective Study was a multicenter inception trial based in the United Kingdom (UK) that recruited participants between 2001 and 2011, with a 5-year follow-up period through 2016. A total of 832 children (70% women; median age at disease onset, 5.9 years) were enrolled, carrying diagnoses of either oligoarticular arthritis (68%) or rheumatoid factor (RF)-negative (27%) or RF-positive polyarticular arthritis (5%). At 1 year postdiagnosis, and annually thereafter for up to 5 years, patients were evaluated for CID using cJADAS10 and Wallace criteria, and for MDA using cJADAS10. Regression analyses were used to calculate odds ratios (ORs) for long-term outcomes.

At the 1-year follow-up, 21% of patients had reached CID according to both Wallace and cJADAS10 criteria, whereas 7% reached CID with only Wallace criteria and 16% had reached CID with only cJADAS10. In addition, 56% of participants achieved no CID, regardless of definition. There was a 10% differential (48% vs 38%) between participants who achieved only MDA and those who fully progressed to CID according to cJADAS10.

Achievement of CID at 1 year, regardless of definition, was associated with increased odds of no limited joints (OR, 9.3; 95% CI, 4.9-17.7; P < .001, for combined criteria). Satisfying both criteria resulted in better functional (P < .001) and psychosocial (P = .007) outcomes. However, achieving CID with cJADAS10 alone was linked to better functionality (OR, 4.5; 95% CI, 2.2-9.5; P < .001) or psychosocial health (coefficient 5.3; 95% CI, 0.5-10.1; P = .029) during follow-up. Compared with participants who only achieved MDA on the cJADAS, participants who only achieved CID with cJADAS10 had lower pain visual analogue scale scores (coefficient, 6.5 mm; 95% CI. 0.9-12.1 mm; P = .023) and greater odds of no limited joints (OR, 2.4; 95% CI 1.3-4.5; P = .006) at 1 year.

Study strengths included a large patient sample treated within a single healthcare system, extensive data collection, and robust imputation methods to handle missing data. Study limitations included the inability to use certain disease activity variables as outcomes because of their inclusion as indicators of CID; limited relevance to only oligoarthritis and polyarthritis; inability to use the 2011 American College of Rheumatology criteria for CID, secondary to lack of morning stiffness data; and a lack of a structured treat-to-target strategy in the UK during the study period, which prevented attribution of improved outcomes to deliberate therapy.

Although MDA may have some utility as a target for patients with more limited disease activity, the results suggest that CID using cJADAS10 criteria is the better option for evaluating patients with more extensive JIA, as it relates to predicting both short- and long-term outcomes. However, the optimal definition of CID in this context remains unclear and imprecise, and should be investigated further.

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Reference

Shoop-Worrall SJ, Verstappen SM, Mcdonagh JE, et al. Long term outcomes following achievement of clinically inactive disease in juvenile idiopathic arthritis: the importance of definition [published online April 12, 2018]. Arthritis Rheumatol. doi: 10.1002/art.40519