Objective To evaluate the effect of achieving a negative postinduction antineutrophil cytoplasmic antibody ANCA) assay on the risk of relapse, end-stage renal disease (ESRD) and death in ANCA-associated vasculitis (AAV).
Methods We emulated a target trial using observational data from the Mass General Brigham AAV cohort comparing patients who achieved versus did not achieve serological remission (negative ANCA assay) within 180 days of induction. Outcomes were relapse, ESRD or death within 5 years, obtained from medical records, the US Renal Data System and the National Death Index. We placed a ‘clone’ of each patient in both trial arms, censored those deviating from their assigned protocol and weighted each by the inverse probability of censoring. Outcomes were assessed by pooled logistic regression.
Results The study included 506 patients with AAV. The mean age was 61 years (SD 18) and the majority were women (58%), white (87%), myeloperoxidase-ANCA+ (72%) and had renal involvement (68%). Rituximab (59%) or cyclophosphamide (33%) was most often used for induction treatment. Within 5 years, 81 (16%) died, 51 (10%) had ESRD and 64 (13%) had relapse. Patients treated to a negative ANCA assay within 180 days had HR 0.55 (95% CI 0.38 to 0.81) for relapse and HR 0.87 (95% CI 0.61 to 1.25) for the composite of ESRD or death within 5 years.
Conclusions In this emulated target trial from a large AAV cohort, achieving serological remission within 180 days of induction was associated with lower risk of relapse, but no statistically significant difference in ESRD or mortality outcomes.
- systemic vasculitis
- granulomatosis with polyangiitis
- autoimmune diseases
Data availability statement
Data available upon reasonable request and with appropriate institutional review board approval.
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Handling editor Josef S Smolen
Contributors GM, YZ and ZSW had access to the study data, developed the figures and tables and vouch for the data and analyses. XF and YZ performed the statistical analyses and contributed to data quality control, data analysis and interpretation of the data. GM, ZSW, CC, CA, BD, JH, JHS, HKC and YZ contributed to data collection, data analysis and interpretation of the data. ZSW directed the work, designed the data collection methods, contributed to data collection, data analysis and interpretation of the data and had final responsibility for the decision to submit for publication. All authors contributed intellectual content during the draft and revision of the work and approved the final version to be published. ZSW accepts full responsibility for the finished work and/or the conduct of the study, had access to the data and controlled the decision to publish.
Funding GM is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR055855). ZSW is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23AR073334 and R03AR078938), the Rheumatology Research Foundation (K Supplement) and a COVID-19 Junior Investigator Award from the Massachusetts General Hospital Department of Medicine.
Competing interests ZSW has performed consultancy for Viela Bio/Horizon, MedPace, Zenas Biopharma and Sanofi/Principia. ZSW has received grant support from BMS and Sanofi/Principia for unrelated work.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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