Table 1

Eligibility criteria for studies included in the systematic review (SR)

CriteriaInclusion criteriaRationale
Inclusion criteriaPopulation
Age: adults (≥18 years)
Gender: anyThe patient population has been restricted to adults, both genders, with diagnoses of RA, SpA, Ps, CD or IBD
Race: any
Disease: RA, SpA, Ps, CD or UC
Intervention
Infliximab
Adalimumab
Etanercept
The review included pharmacological interventions, which are used in clinical practice for RA, SpA, Ps, CD or IBD. Different formulations or route of administration of the same drug were included as supplement evidences
Comparator
Any of the included interventions
Placebo
These comparators were selected to potentially enable the comparison of different drug responses
Outcomes
Drug response, assessed by:
 – the European League Against Rheumatism (EULAR) criteria for RA.59 EULAR good and moderate responders were included within the responder group.Therapeutic responses were defined according to the internationally defined criteria for each disease. In IBD patients, therapeutic responses are often defined by an expert physician, in routine clinical practice.
The review was not restrictive regarding the assay employed to assess ADA, if described.
 – the Assessment in Ankylosing Spondylitis 20% response criteria or Ankylosing Spondylitis Disease Activity Score for SpA,60 61
 – the Psoriasis Area and Severity Index for Ps62
 – Empirically by an expert physician for IBD.
ADA detection
Study design
Controlled Clinical Trials and Observational studies
published in peer-reviewed journals.
Unpublished data, ‘recommendations’, reviews and MAs were excluded from the analysis but used to hand-search additional bibliographic references.
Randomized Clinical Trials (RCTs) are the gold standard of clinical evidence, minimising the risk of confounding and allowing the comparison of the efficacy of interventions. To enhance the level of evidence, observational studies were included
Phases of trial
All phases
All phases of trials evaluating pharmacological interventions were included to avoid missing of any potential study
Language restrictions
No Language Restriction
The SR was meant to be as complete as possible.
Publication timeframe
No date or publication status restrictions were imposed.
The SR was meant to be as complete as possible
Exclusion criteriaPopulation
Study population limited to a known type of drug response (ex. non-responders)
We are interested in the comparison between responders and non-responders
ExposureADA assessed outside the trough period or before week 6To avoid drug interference if outside the trough period; and to minimise false negative results before week 6 (for the majority of patients ADA became detectable between 12-weeks and 24 weeks of treatment).2 4 12 14
Whenever ADA were assessed at multiple time points, we selected the measurement closest to (a) the last evaluation or (b) the majority of the follow-up times of the included studies.
Assay not specified
Studies without a specified IS or administration schedule (to address the influence of IS on ADA detection).
  • ADA, anti-drug antibodies; CD, Crohn's Disease; IBD, Inflammatory Bowel Diseases; IS, immunosuppression; MA, meta-analysis; Ps, Psoriasis; RA, Rheumatoid Arthritis; RCTs, Randomized Clinical Trials; SpA, Spondyloarthritis; UC, Ulcerative Colitis.