Biosimilar Switching Maintained Disease Control in People With Ankylosing Spondylitis

Biologic therapy reaches fewer than half of eligible patients with ankylosing spondylitis in many health care systems—not because the treatments don't work, but because they cost up to $30,000 a year per patient.¹

Biosimilar tumor necrosis factor inhibitors, which offer cost reductions of 15% to 35% compared with reference biologics, have emerged as a strategy to expand treatment access for people with ankylosing spondylitis, a chronic inflammatory condition that causes progressive spinal pain and stiffness. | Image credit: MQ-Illustrations - stock.adobe.com

A structured narrative review published in Frontiers in Pharmacology synthesized evidence from randomized controlled trials (RCTs), real-world registries, and regulatory approval programs to assess whether people with ankylosing spondylitis who were stable on reference tumor necrosis factor (TNF) inhibitors could safely transition to biosimilar formulations.²

Researchers from Yunnan University of Chinese Medicine conducted the review in response to a recognized evidence gap: although biosimilar switching guidance had been developed for rheumatoid arthritis, ankylosing spondylitis-specific switching data—most of which emerged after 2018—had not been systematically synthesized.

The review covered literature published between January 2013 and March 2025 across PubMed, EMBASE, and the Cochrane Library. Although the authors are based in China, the evidence they synthesized spans multinational registries and trials conducted across Europe, Asia, and North America, making the findings relevant to US payers and health systems navigating biosimilar formulary decisions.

Ankylosing spondylitis affects an estimated 0.2% to 0.5% of adults worldwide, and reference TNF inhibitors—approved for AS between 2003 and 2016—carry annual costs ranging from $15,000 to $30,000 per patient in the US.¹ Biosimilar alternatives typically offer 15% to 35% cost reductions, with deeper discounts available through competitive procurement. Despite this economic case, clinical uptake has depended on confidence that switching stable patients does not disrupt disease control. Ankylosing spondylitis poses unique considerations compared with other inflammatory conditions: patients often require prolonged biologic therapy, use different validated monitoring instruments, and may experience chronic axial pain in ways that heighten susceptibility to the nocebo effect.

What the Trial Evidence Showed

The most methodologically rigorous switching data came from the PLANETAS extension study, which followed 174 people with ankylosing spondylitis after an initial 54-week trial establishing equivalence between the infliximab biosimilar CT-P13 and reference infliximab in 250 treatment-naive patients.

In the extension, 88 patients continued CT-P13, and 86 switched from reference infliximab to CT-P13. At week 102, Assessment of SpondyloArthritis International Society (ASAS)-20 response rates were 80.7% in the maintenance group and 76.9% in the switching group, with ASAS-40 and partial remission rates similar between groups.

Anti-drug antibody positivity was 23.3% in the maintenance group and 27.4% in the switching group—a difference that was not statistically significant and did not indicate increased immunogenic risk after the transition. Adverse event-related discontinuation occurred in 3.3% of people who maintained CT-P13 and 4.8% of those who switched.

A separate 18-month Greek RCT randomized 88 people with ankylosing spondylitis in clinical remission to either switch to a biosimilar (n = 45) or continue the reference product (n = 43). All patients who completed the study maintained clinical remission, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP showing no significant between-group differences. Erythrocyte sedimentation rate and C-reactive protein (CRP) values remained stable and comparable across groups.

Real-World Registry Data

Registry evidence from multiple countries corroborated trial findings at a larger scale. The Korean College of Rheumatology Biologics (KOBIO) registry reported a 4-year retention rate of 66% among 244 people receiving CT-P13, with BASDAI remaining well-controlled throughout follow-up. A propensity score-matched KOBIO analysis of 248 patients found 3-year retention rates of 64.2% for CT-P13 vs 55.6% for reference infliximab—a nonsignificant difference.

The French ReFLECT study, which followed 411 patients with rheumatic diseases, including ankylosing spondylitis, over 24 months, reported a retention rate of 74.9%, with inflammatory markers remaining stable in patients who had switched. A Nordic collaborative analysis pooling data across five countries found no significant retention differences between biosimilars and reference products for either infliximab or etanercept in 2,334 biologic-naive people with spondyloarthritis.

The authors identified several important caveats. The PLANETAS extension used an open-label design, introducing potential bias in patient-reported outcomes such as BASDAI, which depends entirely on self-report. The Greek RCT was limited by a small sample size and performed a completers analysis rather than intention-to-treat, meaning patients who discontinued—including 4 in the biosimilar group attributed to nocebo effects—were excluded before efficacy analysis.

Registry studies could not fully exclude selection bias or unmeasured confounders, as clinicians may have preferentially switched more clinically stable patients. Existing datasets also rarely distinguished between clinician-initiated and administratively mandated switching, which the review identified as a meaningful gap given evidence that mandated switching without patient engagement drove higher discontinuation rates.

The available switching evidence was also heavily concentrated on CT-P13; data for etanercept and adalimumab biosimilars in ankylosing spondylitis populations remained sparse, drawn largely from mixed inflammatory arthritis cohorts with small AS subgroups.

The review emphasized that nocebo effects—symptom worsening driven by negative expectations rather than pharmacological change—contributed meaningfully to switching discontinuations in mandatory programs.

Dutch data showed approximately 25% of people discontinued biosimilar therapy within 6 months when switching occurred as a payer-mandated policy without individualized clinical assessment, with many discontinuations linked to subjective complaints unsupported by objective inflammatory markers.

Programs that incorporated shared decision-making and patient education reported lower discontinuation rates.

References

1. Zhu W, He X, Cheng K, et al. Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res. 2019;7:22 doi:10.1038/s41413-019-0057-8
2. Cai L, Chen X, Fang Y, et al. Clinical evidence and implementation guidance for biosimilar switching in ankylosing spondylitis. Front Pharmacol. 2026;17:1803260. doi:10.3389/fphar.2026.1803260