Prevalence and clinical relevance of anti-drug antibodies in psoriatic arthritis: a systematic review
James Kimpton, Akpabio Akpabio, Andrew Watts, Sarah Tansley, Theresa Smith, Neil McHugh, William TillettObjectives
To determine the prevalence of anti-drug antibodies (ADAs) in patients with psoriatic arthritis (PsA) treated with biological disease-modifying antirheumatic drugs (bDMARDs) and to evaluate associations with serum drug levels, clinical efficacy and safety.
Methods
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review was conducted. MEDLINE, Embase and Cochrane CENTRAL were searched from inception to September 2025. Randomised controlled trials and observational studies reporting ADA measurement in adults with PsA receiving bDMARDs were included. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2 and the Risk of Bias in Non-randomised Studies of Interventions.
Results
28 studies (19 randomised controlled trials and 9 observational studies) were included. ADA prevalence varied widely between bDMARDs and across studies of the same drug and was not directly comparable due to immunoassay heterogeneity. The highest ADA prevalence was observed with adalimumab, infliximab and golimumab followed by ustekinumab, ixekizumab, certolizumab pegol and guselkumab, while secukinumab and etanercept demonstrated very low or absent immunogenicity. Across tumour necrosis factor (TNF) inhibitor studies, ADAs were consistently associated with lower serum drug levels and reduced clinical response, while concomitant methotrexate was associated with lower ADA prevalence. In contrast, serum drug level and clinical outcome data for interleukin (IL)-17, IL-12/23 and IL-23 inhibitors were limited or lacking. Immunogenicity-related adverse events were uncommon, and evidence was insufficient to establish an association with ADAs across bDMARDs.
Conclusion
ADA prevalence in PsA varies widely between bDMARDs and across studies of the same bDMARD. ADAs appear most clinically relevant for TNF inhibitors, whereas evidence for other biological classes remains limited. Immunoassay heterogeneity limits comparability, highlighting the need for standardised prospective studies.
PROSPERO registration number
CRD420251121662.