Guide
Systemic juvenile idiopathic arthritis (sJIA) is a rare autoimmune disease with symptoms such as fever, rash, and joint pain, which may lead to complications such as growth retardation and macrophage activation syndrome (MAS). Traditional treatments for sJIA include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and traditional synthetic disease-modifying antirheumatic drugs. Early treatment of sJIA is important to prevent joint injury and disability and to control systemic symptoms, but some patients have difficulty adequately controlling the disease with traditional treatment options, and long-term use of corticosteroids can have a variety of side effects.
Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeting interleukin-6 (IL-6) receptors, which plays an important role in the pathogenesis of sJIA. In October 2016, tocilizumab was approved in China for the treatment of sJIA, and given the limited data on TCZ for the treatment of sJIA in China, this study evaluated the efficacy and safety of TCZ in Chinese sJIA patients for 52 weeks.
Study design
✦
✦
✦
The study was a single-arm, open-label, phase IV trial conducted at 10 centers in China, including a 52-week open-label period (every 2 weeks follow-up) and an 8-week safety follow-up period. Patients aged 2 to 17 years in China who had been diagnosed with sJIA for more than 6 months and who had an inadequate clinical response to NSAIDs/corticosteroids were included. Patients are treated with TCZ injections every 2 weeks.
Primary efficacy endpoint: To assess the proportion of patients who achieve a JIA-United States College of Rheumatology (JIA-ACR) 30 response without fever at week 12; Secondary efficacy endpoints: To assess the overall efficacy and persistence of TCZ; Exploratory endpoint: To evaluate the impact of treatment on patients' quality of life [using the Child Health Assessment Questionnaire Pain Score (CHAQ) and Child Health Questionnaire-Parent Form 50 (CHQ-PF50)], to analyze inflammatory markers; Safety endpoints: Adverse events (AEs), serious adverse events (SAEs), vital signs, and clinical laboratory tests were assessed.
Findings:
✦
✦
✦
A total of 62 patients (TCZ 12 mg/kg (<30 kg), n=34; TCZ 8 mg/kg (≥30 kg), n=28] were included in the intention-to-treat (ITT) and safety analyses, of which 56 patients completed the study and 6 patients discontinued the study due to AEs, physician decisions, or patient/guardian withdrawal.
Primary endpoint
At week 12, 87.1% (54/62) of patients achieved JIA-ACR30 response without fever (Fig. 1A), of which 82.4% (28/34) achieved JIA-ACR30 response in the 12 mg/kg group and 92.9% (26/28) achieved JIA-ACR30 response without fever in the 8 mg/kg group (Fig. 1B).
Secondary endpoints
From week 12 to week 52, the proportion of JIA-ACR30/50/70/90 responders increased rapidly (Figure 1A). 87.1% (54/62) of the patients in the overall population achieved a JIA-ACR30 response without fever at week 52, and the proportions of JIA-ACR30/50/70/90 responders were 88.7%, 83.9%, 62.9%, and 27.4% at week 12, 83.9%, 83.9%, 74.2%, and 48.4% at week 24, and 90.3%, 87.1%, 85.5%, and 67.7% at week 52, respectively (Figure 1B). The proportion of patients without active disease at weeks 24 and 52 was 19.4% and 35.5%, respectively.
Figure 1: Proportion of patients with different responses
A、JIA-ACR30/50/70/90应答者(ITT人群)按周占比;B、第12周JIA-ACR30应答且无发热者及JIA-ACR30/50/70/90应答者比例(ITT人群)
In addition, the study found that high-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks of TCZ treatment, and 44 of the 58 patients (75.9%) with high baseline hsCRP (> upper limit of normal) recovered at week 52 (Figure 2). In addition, the dose of corticosteroids was tapered from week 20 onwards, with 27.4% of patients discontinuing corticosteroids at week 52 (Figure 3).
Figure 2: Mean hsCRP levels over time (ITT population)
Figure 3: Change in mean corticosteroid dose over time (ITT population)
Exploratory endpoints
In terms of quality of life improvement, patients treated with TCZ showed the mean CHAQ pain score (baseline: 48.3; week 52: 5.5), CHAQ disability index score (baseline: 0.71; week 52: 0.11), CHQ physical (baseline: 23.4; week 52: 44.4) and psychological (baseline: 41.3; week 52: 50.8) social global score, and parental/ Patients' assessments of global well-being (baseline: 56.7; week 52: 9.3) improved. In addition, the patient's height standard deviation score increased from baseline at week 52 (baseline: -1.15; week 52: 1.04), suggesting catch-up growth after TCZ treatment. In terms of serological indicators, the patient's hemoglobin level increased (19.2 g/L increase from baseline at week 52), platelets (baseline: 501.9×109/L, week 52: 267.4×109/L) and white blood cell count (baseline: 14.3×109/L; Week 52: 7.3×109/L) decreased.
Security analysis
All patients experienced at least 1 AE over the course of the study, 88.7% reported treatment-related AEs, 24.2% reported grade ≥3 AEs, 16 patients reported AEs leading to treatment discontinuation, 4 patients reported AEs leading to study discontinuation, no death or macrophage activation syndrome (MAS) events were reported, and the most common AE was upper respiratory tract infection.
Research Discussion and Conclusions
✦
✦
✦
This study evaluated the long-term (52-week) efficacy and safety of TCZ in Chinese sJIA patients, and the results showed that TCZ had good clinical efficacy in the target population. During TCZ treatment, the patient's systemic symptoms and arthritis were effectively improved, and the inflammatory indicators improved rapidly. In addition, early treatment with TCZ may have additional benefits, such as a tapered reduction in the dose of corticosteroids, increased patient growth rate, and improved quality of life.
Taken together, the results of this study report the long-term (52-week) efficacy and safety of tocilizumab in Chinese patients with sJIA, and the patient safety outcomes are consistent with the known safety profile of tocilizumab.
参考文献：Li C, Tang X, Zhou Z, et al. Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial. Clin Rheumatol. Published online September 16, 2024. doi:10.1007/s10067-024-07126-9
Yimaitong is a professional online doctor platform, and the mission of the platform is to "sense the pulse of the world's medicine and help China's clinical decision-making". Yimaitong has a series of products such as "Clinical Guidelines", "Medication Reference", "Medical Literature King", "Yizhiyuan", "eYantong" and "ePulse", which fully meet the needs of medical workers in clinical decision-making, obtaining new knowledge and improving scientific research efficiency.