Impaired cardiorespiratory and neuromuscular fitness in children and adolescents with juvenile idiopathic arthritis: a cross-sectional case–control study in the era of biologic drug therapies

**Background:** Juvenile idiopathic arthritis (JIA) is one of the most common immune-mediated inflammatory diseases in children, with a European prevalence of 32.6 per 100,000. Biologic drug therapies have improved overall outcomes, but studies on physical fitness in JIA patients have been inconsistent. This study aimed to comprehensively assess cardiorespiratory and neuromuscular fitness in children with JIA in the era of biologic therapies.

**Methods:** This cross-sectional case–control study recruited 73 JIA patients (25 boys, 48 girls; mean age 11.8 ± 3.01 years) from Kuopio (n=48) and Tampere (n=25) University Hospitals between 2017–2019. Diagnoses included oligoarthritis (n=18), extended oligoarthritis (n=10), RF-negative polyarthritis (n=41), psoriatic arthritis (n=1), systemic arthritis (n=1), and undifferentiated arthritis (n=2). For each patient, an age- and sex-matched healthy control was selected from the PANIC study or national registry. Cardiorespiratory fitness was assessed by maximal ergospirometry on a cycle ergometer with direct breath-by-breath respiratory gas analysis. Neuromuscular fitness was assessed via 50-m shuttle run, sit-up test (30 s), handgrip strength (vigorimeter), standing long jump, modified flamingo balance test, and box and block test. Physical activity and sedentary time were assessed by the PANIC Physical Activity Questionnaire. Disease activity was measured using JADAS-10, with cut-offs of ≥0.6 (oligoarthritis) and ≥0.8 (polyarthritis) for active disease.

**Key Results:** JIA patients had significantly lower cardiorespiratory fitness than controls: Wmax/kg (2.80 ± 0.54 vs. 3.14 ± 0.50 Watts/kg, p<0.01) and VO2peak/kg (38.7 ± 7.53 vs. 45.8 ± 6.59 ml/min/kg, p<0.01). Neuromuscular fitness was also impaired: shuttle-run time was longer (24.4 ± 3.58 vs. 21.6 ± 1.93 s, p<0.01), sit-ups were fewer (14.6 ± 5.55 vs. 18.1 ± 5.61 per 30 s, p<0.01), and standing long jump was shorter (1.42 ± 9.52 vs. 1.60 ± 3.90 m, p<0.01). Handgrip strength was lower in the left hand (64.3 ± 24.7 vs. 74.1 ± 8.60 kPa, p<0.05) but not the right. Balance and box and block test results did not differ significantly. JIA patients were less physically active (89.0 ± 44.7 vs. 112.7 ± 62.1 min/day, p<0.05) and had more sedentary time (427 ± 213 vs. 343 ± 211 min/day, p<0.05). Only 59% of JIA patients met the recommended 60 min/day of physical activity vs. 82% of controls (p=0.037). No differences in fitness or physical activity were found between active vs. inactive disease groups or between oligoarticular vs. polyarticular disease groups. In multivariate regression, male sex and lower ISO-BMI were independently associated with higher Wmax/kg (R²=0.431); male sex, higher physical activity, and lower ISO-BMI with higher VO2peak/kg (R²=0.374). Disease activity, biologic medication, and glucocorticoid dose did not correlate with fitness parameters.

**Clinical Implications:** Despite modern biologic therapies, children with JIA have significantly impaired cardiorespiratory and neuromuscular fitness compared to healthy peers, driven largely by lower physical activity and higher sedentary behavior rather than disease activity itself. These findings highlight the need to incorporate physical activity promotion into routine multidisciplinary JIA care to mitigate cardiovascular and musculoskeletal health risks. The lack of association between disease activity and fitness suggests that even patients with well-controlled disease may benefit from structured exercise interventions.