Comparable Disease Activity, Drug Persistence in Patients With JIA Who Switch to Biosimilars

Switching children and young people with juvenile idiopathic arthritis (JIA) from anti-tumor necrosis factor (TNF) originators to biosimilars showed similar disease activity and drug persistence compared to those continuing the originators, with a low rate of switching back, in a recent study.¹

The results indicated good tolerability of non-medical switching between reference and biosimilar TNF inhibitors. The authors conducted the analysis to address the lack of data on the outcomes of children and young people with JIA who are switched from anti-TNF originators to biosimilars for non-medical reasons, particularly regarding drug survival and disease activity. The findings provide much-needed evidence that supports the safety and effectiveness of non-medical switching, reassuring patients, families, and clinicians about the use of biosimilars in this population.

Regarding biosimilar TNF inhibitor accessibility, patients in the UK have access to 10 approved adalimumab biosimilars, 4 infliximab biosimilars, and 3 etanercept biosimilars, all of which were approved by the European Medicines Agency (EMA) prior to the UK leaving the European Union.² Additionally, the UK’s Medicines and Healthcare products Regulatory Agency has declared all biosimilars as being interchangeable with their reference agents upon approval.³

Approximately 12,000 children and young people in the UK are affected by JIA, which equates to 1 in every 1,000 children under the age of 16.⁵ | Image credit: anut21ng Stock - stock.adobe.com

However, another recent study found that there remains a lack of understanding and/or confidence in biosimilars among providers and patients, leading to diminished provider willingness to prescribe biosimilars and patient perceptions about the safety of switching to a biosimilar.⁴ The authors of the present study also noted that studies for adalimumab and etanercept biosimilars tend to be in rheumatoid arthritis populations, leaving some providers, patients, and caregivers to question the safety of extrapolated indications.¹

“The results from this analysis will be reassuring to clinicians, patients, and their families considering a non-medical switch, and suggests good tolerance of non-medical switching in this patient population,” the authors wrote.

The present study relied on data from the UK JIA Biologics Register, focusing on children younger than 16 years with JIA starting biological or targeted synthetic disease-modifying antirheumatic drug therapy by July 7, 2023. Patients with systemic JIA or those who began treatment over 6 months before registration were excluded. The study aimed to compare the effectiveness of biosimilars with originator drugs in controlling arthritis.

Participants were drawn from 2 national cohorts, with data collected at the start of therapy and during follow-up at 6 months, 1 year, and annually. Patients switching to biosimilars were matched with those continuing originator therapy based on key characteristics. The study assessed drug survival using Kaplan-Meier estimates and treatment discontinuation risks with Cox proportional hazard models. Disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS-71) at the start and 6 months post-switch. Statistical analyses included multiple imputation for missing data, with sensitivity analyses conducted for adalimumab therapy.

The study analyzed 224 children and young people with non-systemic JIA who transitioned from an originator to a biosimilar between January 1, 2017, and July 7, 2023. Most patients (64%) switched from reference adalimumab to a biosimilar, with 75% of these having initiated adalimumab as their first biological therapy. The median age at the start of the originator therapy was 11 years, and 14 years at the switch to the biosimilar. The cohort was predominantly female (62%) and White (88%).

Out of the 209 patients with follow-up data, 164 were matched with patients who continued on the originator therapy for comparative analysis. The median age at the time of switching was 13 years, and the median disease duration was 5 years. The study found that 31% of patients in the biosimilar group discontinued treatment during a median follow-up of 2 years, compared to 40% in the originator group over a median follow-up of 2.2 years.

The study found no significant difference in treatment discontinuation rates between those who switched to biosimilars and those who continued on the originator (HR, 1.46; 95% CI, 0.93-2.30). At 1-year post-switch, 76% (95% CI, 68-82) of biosimilar patients and 87% (95% CI, 79-92) of originator patients remained on therapy. At 2 years, 64% (95% CI, 54-72) of biosimilar patients and 70% (95% CI, 59-79) of originator patients were still on therapy.

Of the 51 patients who stopped biosimilar treatment, 35% switched back to the originator, with a median time to restart the originator of 0 days (IQR, 0-14), and 55% switched to a different biological therapy due to ineffectiveness. Injection-related issues, such as stinging or painful injections, were reported by 22% of those who discontinued biosimilars, with 8 patients returning to the originator.

Regarding disease activity, there was insufficient evidence to indicate a clinically significant worsening in those who switched to biosimilars compared to those who continued on the originator, with an odds ratio (OR) of 0.71 (95% CI, 0.34-1.51). Specifically for adalimumab, the HR for treatment discontinuation was 1.70 (95% CI, 0.90-3.21), and the OR for worsening disease activity 6 months after the switch was 0.69 (95% CI, 0.27-1.74). There was no significant difference in the change in disease activity score from the index date to 6 months between the cohorts.

Limitations included potential misclassification of disease activity for early treatment stoppers, difficulty interpreting unadjusted JADAS-71 changes, unmatched patients with rare characteristics, unmeasured confounders, and low patient numbers limiting drug-specific analyses.

References

1. 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

2. Biosimilar approvals. The Center for Biosimilars^®. Updated March 22, 2024. Accessed August 26, 2024. https://www.centerforbiosimilars.com/biosimilar-approvals

3. Hagen T. The Brexit rollout from the biosimilars perspective. The Center for Biosimilars. March 26, 2021. August 26, 2024. https://www.centerforbiosimilars.com/view/the-brexit-rollout-from-the-biosimilars-perspective

4. Jeremias S. Biosimilar adoption in the UK: patient and consultant views on safety and switching. The Center for Biosimilars. June 26, 2024. Accessed August 26, 2024. https://www.centerforbiosimilars.com/view/biosimilar-adoption-in-the-uk-patient-and-consultant-views-on-safety-and-switching

5. Juvenile idiopathic arthritis. National Rheumatoid Arthritis Society. Accessed August 26, 2024. https://nras.org.uk/resource/juvenile-idiopathic-arthritis/