Adalimumab, Etanercept Biosimilars Deliver Real-World Results for Juvenile Idiopathic Arthritis

As high-cost originator biologics continue to limit access for children with juvenile idiopathic arthritis (JIA), biosimilars are emerging as promising, affordable alternatives.

A new systematic review and meta-analysis of 5 real-world observational studies found that biosimilars for etanercept (Enbrel) and adalimumab (Humira) performed similarly to their originator drugs in controlling disease activity and minimizing adverse events.1 Published in Seminars in Arthritis and Rheumatism, the findings could help expand treatment access while reinforcing confidence in biosimilar use across pediatric rheumatology.

Adult trials have shown similar efficacy and safety between infliximab biosimilars and its originator, but pediatric data are lacking. | Image credit: LaMorenita – stock.adobe.com

“These findings echoed the observations from adult studies, and would likely instill more confidence in prescribers, patients, and families in their use of biosimilar therapy,” the authors said. “This would hopefully also provide supporting information for licensing authorities in their regulation of use of these biosimilars in the pediatric population in their respective countries or regions.”

Etanercept Biosimilars: Comparable Disease Control Even After Switching

Etanercept biosimilars were the most studied in the review, featured in 4 of the 5 included studies. In an Italian single-center cohort, children with JIA who received biosimilars had significantly lower Juvenile Arthritis Disease Activity Scores (JADAS-10) and relapse rates compared with those receiving the originator over 24 months (35.7% vs 72.5%; P < .01).2 However, larger registry-based studies reported more similar outcomes between groups.1

For example, the German BIKER Registry followed biologic-naïve children with JIA and found comparable median JADAS-10 scores and joint counts among those started on etanercept biosimilars vs originator Enbrel.3 Additionally, disease activity remained stable in patients who switched from Enbrel to a biosimilar, with no increase in patient or physician global assessments. These results suggest etanercept biosimilars can be confidently used both at treatment initiation and after switching, warranting further research into the treatment’s flexibility and associated cost savings.1

Adalimumab Biosimilars: Effective as First-Line or After Originators

Adalimumab biosimilars were assessed in 4 studies, including the multicenter OBSIDIAN cohort from Italy.4 Here, children with JIA treated with either biosimilar or originator adalimumab showed similar time to remission (HR, 1.67; 95% CI, 0.59-3.94) and comparable disease activity at 3, 6, and 12 months after the switch.

Similarly, data from the UK JIA Biologics Register showed no clinically meaningful difference in JADAS-71 scores among children and young adults who switched from Humira to a biosimilar compared with those who stayed on the originator (adjusted OR for worsening, 0.71; 95% CI, 0.34-1.51).5 A study from Turkey also reported comparable median JADAS-10 scores between children on original and biosimilar adalimumab over a follow-up period of 24 months.6 Like etanercept, these studies support both initiating and switching to adalimumab biosimilars without sacrificing disease control.

“All studies consistently showed that biosimilars were similarly efficacious, if not better, in JIA patients in terms of their JADAS scores when compared to those on originators,” the review authors said.1 “Furthermore, there were no increased rates of adverse events when JIA patients were treated with biosimilars.”

Infliximab Biosimilars: Limited Pediatric Data but Promising Equivalence

Adult clinical trials have demonstrated that biosimilar anti–tumor necrosis factor therapies have similar efficacy and safety to originator Remicade for rheumatic conditions, but pediatric data is lacking. The 30-week PLANETRA trial (NCT01217086) first confirmed this with infliximab biosimilar CT-P13 in rheumatoid arthritis7; the 52-week NOR-SWITCH (NCT02148640) trial later showed noninferiority after switching from originator infliximab to CT-P13 across multiple autoimmune diseases.8

Overall, adverse event rates were similar between biosimilars and originators (OR, 0.78; 95% CI, 0.52-1.17), reinforcing their safety, according to the authors.1

“We hope to update this review when more published data from high-quality studies become available subsequently to further validate these findings and enhance generalizability,” they wrote.

References

1. Huang J, Teh KL, Chen C, Das L, Arkachaisri T. Efficacy and safety of anti-tumor necrosis factor-α biosimilars in juvenile idiopathic arthritis - a systematic review and meta-analysis. Semin Arthritis Rheum. Published online July 16, 2025. doi:10.1016/j.semarthrit.2025.152792
2. Gicchino MF, Capasso G, Amodio A, Miraglia Del Giudice E, Olivieri AN, Di Sessa A. Biosimilars versus originators in children with juvenile idiopathic arthritis: a real-world experience. J Pediatr Health Care. 2025;39(1):88-92. doi:10.1016/j.pedhc.2024.08.003
3. Thiele F, Klein A, Hospach A, et al. Efficacy and safety of etanercept biosimilars compared with the originator for treatment of juvenile arthritis: a prospective observational study. ACR Open Rheumatol. 2021;3(11):779-787. doi:10.1002/acr2.11325
4. Maccora I, Lombardi N, Crescioli G, et al. OBSIDIAN - real-world evidence of originator to biosimilar drug switch in juvenile idiopathic arthritis. Rheumatology (Oxford). 2022;61(4):1518-1528. doi:10.1093/rheumatology/keab572
5. Kearsley-Fleet L, Baildam E, Beresford MW, et al. Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study. Lancet Rheumatol. 2024;6(7):e438-e446. doi:10.1016/S2665-9913(24)00087-0
6. Ulu K, Çakan M, Çağlayan Ş, et al. Real-life data on efficacy and safety of original adalimumab and biosimilar adalimumab (ABP 501) in pediatric rheumatic diseases. Expert Opin Biol Ther. 2023;23(8):833-839. doi:10.1080/14712598.2022.2123703
7. Yoo DH, Hrycaj P, Miranda P, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613-1620. doi:10.1136/annrheumdis-2012-203090
8. Goll GL, Jørgensen KK, Sexton J, et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J Intern Med. 2019;285(6):653-669. doi:10.1111/joim.12880