Table 6.

Terms for anti-drug antibody (ADA) response origin and frequency

Term	Definition
Treatment-induced ADA-positive subject	Subject with ADA developed de novo (seroconverted) following biopharmaceuticals (BP) administration (i.e. formation of ADA any time after the initial drug administration in a subject without pre-existing antibodies)
Treatment-boosted ADA-positive subject	Subject with pre-existing antibodies that develops an increased level of ADA following BP administration (i.e. any time after the initial drug administration the ADA titre is disproportionately greater by a biologically relevant margin, such as two- or threefold relative to the baseline titre)
Treatment-unaffected ADA-positive subject	Subject with pre-existing ADA level that does not change following the BP administration
Incidence of ADA (rate of ADA development)	Measure of the rate of BP-specific ADA immune responses during a defined observation period, usually equal to the sum total of treatment-induced and treatment-boosted ADA-positive subjects (but not treatment-unaffected) as a percentage of the evaluable subject population. Incidence is a cumulative measurement. Incidence rates for treatment-induced ADA treatment-boosted ADA, or specific types of ADA [e.g. non-neutralizing antibodies (Nabs) or immunoglobulin (Ig)E] may also be considered separately. Incidence includes transient and persistent positive patients and may also be referred to as cumulative incidence
Prevalence of ADA (frequency of ADA-positive subjects)	The percentage of subjects positive for ADA in a defined population at a particular time-point or within a particular defined time-frame. For example, antibody prevalence at baseline (pretreatment) is determined by dividing the number of evaluable subjects with antibody-positive pre-treatment samples by the number of subjects with a pretreatment sample result, expressed as a percentage. May also be useful when subjects with diverse treatment histories are sampled randomly