TY - JOUR T1 - Primary and secondary non-response: in need of operational definitions in observational studies JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 961 LP - 964 DO - 10.1136/annrheumdis-2021-220202 VL - 80 IS - 8 AU - Enriqueta Vallejo-Yagüe AU - Edward C Keystone AU - Sreemanjari Kandhasamy AU - Raphael Micheroli AU - Axel Finckh AU - Andrea Michelle Burden Y1 - 2021/08/01 UR - http://ard.bmj.com/content/80/8/961.abstract N2 - Treatment response to biologics and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis (RA) patients can be classified as primary or secondary non-response, based on evidence of an initial response. Conceptually, primary non-response is generally considered if the drug was ineffective, with no clinical response within the initial treatment period, while secondary non-response would be considered if, after an initial response, the effectiveness is lost over time.1–4 Despite these generally accepted definitions, there is no consensus on how to operationalise these concepts. Consequently, the current observational evidence is highly heterogeneous and the prevalence of primary versus secondary failure remains largely unknown.The underlying mechanisms for primary and secondary non-response may differ,3 5 thus, we believe that defining the type of non-response is key to improving patient care. While primary non-response may be due to a mechanistic failure, secondary non-response may be driven by immunogenicity. Previous studies have shown that both the type of non-response and the development of antidrug antibodies (ADAbs) are important factors when predicting the success of the second biologic.6 7 Thus, developing clear definitions of how to operationalise primary and secondary non-response is essential to accelerate research that aims to predict the optimal therapy for a given patient,5 which will, in turn, improve clinical practice recommendations. For example, if a patient is a primary non-responder to a tumour necrosis factor inhibitor (anti-TNF), the best practice would likely be to switch to a biologic with different mechanism of action. However, if the patient was able to achieve clinical response prior to failure (secondary non-responder), it would be reasonable to proceed with another anti-TNF. Additionally, following the growing postmarketing research targeting comparative effectiveness of treatments in RA, agreement on operational definitions would improve cross-study comparisons. Thus, we believe that unifying this terminology would benefit the … ER -