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Serum osteopontin as a predictive marker of responsiveness to methotrexate in juvenile idiopathic arthritis
Laura Masi1, Laura Ricci, Francesco Zulian
1A. Meyer Children's Hospital, University of Florence, Firenze, Italy
Insights
Serum osteopontin (OPN) levels at diagnosis may predict how well children with juvenile idiopathic arthritis (JIA) respond to methotrexate (MTX) treatment. Higher baseline OPN indicates a poorer response to MTX therapy.
Area of Science:
- Rheumatology
- Immunology
- Biomarker Research
Background:
- Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease affecting children.
- Methotrexate (MTX) is a common first-line treatment for JIA, but predicting treatment response remains a challenge.
- Osteopontin (OPN) is a protein implicated in inflammatory processes.
Purpose of the Study:
- To investigate if baseline serum osteopontin (OPN) levels can predict treatment response in children with JIA receiving MTX.
- To assess changes in OPN levels during MTX therapy and subsequent anti-tumor necrosis factor-alpha (anti-TNFα) treatment.
Main Methods:
- Sixty children with active JIA were treated with MTX. Patients were categorized as responders or non-responders after 12 months.
- Serum OPN levels were measured at diagnosis (baseline), 6, and 12 months of MTX treatment.
- Non-responders received additional etanercept (an anti-TNFα therapy) for 12 months, with OPN levels re-evaluated.
Main Results:
- Baseline OPN levels were significantly higher in JIA patients compared to healthy controls (p = 0.0003).
- Non-responders had significantly higher baseline OPN levels than responders (33.2 ± 18.1 μg/ml vs 14.16 ± 10.1 μg/ml).
- MTX treatment reduced OPN levels in both responders and non-responders. Etanercept further reduced OPN levels in non-responders.
Conclusions:
- Serum osteopontin (OPN) levels at baseline show potential as a predictive marker for MTX responsiveness in JIA patients.
- OPN levels decrease with effective treatment, suggesting its role in disease activity.
- This finding may aid in personalizing JIA treatment strategies.
Objective:
To evaluate if serum concentrations of osteopontin (OPN) at baseline in patients with juvenile idiopathic arthritis (JIA) represent a potential predictor of responsiveness to methotrexate (MTX).
Methods:
At diagnosis, 60 children with active JIA received MTX in addition to nonsteroidal antiinflammatory drugs. After 12 months of MTX treatment, 30 patients were defined as responders; the 30 nonresponders received anti-tumor necrosis factor-alpha therapy (etanercept) in addition to MTX; this group was then enrolled for an additional 12-month study period. No patient had received steroids within 6 weeks before entering the study. Fifty healthy children matched for sex and age acted as controls. OPN serum levels were measured at baseline, before MTX, and then at 6 and 12 months. In the nonresponder patients, OPN was evaluated again after 6 and 12 months of etanercept treatment.
Results:
At baseline, OPN values were significantly higher (p = 0.0003) in JIA patients than in controls, with no significant differences among the different JIA subtypes. At baseline, OPN levels were lower in responders than in nonresponder patients (14.16 +/- 10.1 microg/ml vs 33.2 +/- 18.1 microg/ml, respectively). After 12 months of MTX treatment, OPN levels were significantly reduced in comparison to baseline in both responder and nonresponder groups (p = 0.0017, p = 0.0048, respectively). In nonresponders, etanercept significantly reduced OPN levels at 6 and 12-month followup in comparison to baseline (p = 0.002, p = 0.008, respectively). No significant differences were found among OPN levels and disease activity.
Conclusion:
Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.