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Variability in Antinuclear Antibody Testing to Assess Patient Eligibility for Clinical Trials of Novel Treatments for Systemic Lupus Erythematosus
Author(s) -
Pisetsky David S.,
Thompson Dana Kathryn,
Wajdula Joseph,
Diehl Annette,
Sridharan Sudhakar
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40910
Subject(s) - medicine , anti nuclear antibody , serology , negativity effect , clinical trial , cohort , immunology , antibody , autoantibody , psychology , social psychology
Objective In the development of novel therapies for systemic lupus erythematosus, antinuclear antibody ( ANA ) positivity represents a criterion for trial eligibility. Since as many as 30% of patients enrolled in trials have been ANA negative, we evaluated the performance characteristics of immunofluorescence assays ( IFA s) for ANA determinations for screening. Methods This study used 5 commercially available IFA s to assess the ANA status of 181 patients enrolled in a phase II clinical trial for an anti–interleukin‐6 antibody. Enrollment included a detailed review of medical records to verify a historical ANA value. IFA results were related to various clinical and serologic features at enrollment. Results While the frequency of ANA negativity assessed by the central laboratory was 23.8% in a cohort of 181 patients, the evaluated IFA kits demonstrated frequencies of negativity from 0.6 to 27.6%. With 2 IFA kits showing a significant frequency of ANA negativity, positive and negative samples differed in levels of anti–double‐stranded DNA , C3, and presence of other ANA s as well as the frequency of high interferon ( IFN ) expression. Conclusion These findings indicate that, when used for screening, IFA s can vary because of performance characteristics of kits and thus can affect determination of trial eligibility. With kits producing a significant frequency of ANA negativity, ANA status can be associated with other serologic measures as well as the presence of the IFN signature, potentially affecting responsiveness to a trial agent.