Risk Factors for Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Among Patients With Relapse
Ellen Romich1, Joshua F Baker1,2, Thomas R Riley1
1Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia.
Objective:
The objective of the study was to determine risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after reinduction of remission with rituximab and discontinuation of maintenance therapy.
Methods:
This is a post hoc analysis of the RITAZAREM clinical trial. Patients aged 15 years or older with AAV and a positive test for anti-proteinase-3 or anti-myeloperoxidase-ANCA who achieved remission after reinduction with rituximab and glucocorticoids were randomized at month 4 to receive continued rituximab or azathioprine for a maintenance period up to 24 months, followed by observation until relapse or up to 48 months. Generalized estimating equations logistic regression identified baseline and time-varying risk factors for relapse by the next visit for the two study phases: maintenance (months 4-24) and off-treatment (months 24-48).
Results:
Among 170 patients (median [interquartile range] age 59 [48-68] years, disease duration 5 [2-10] years), 99 relapses occurred (46 during maintenance). During maintenance, musculoskeletal involvement (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.1-7.2; P = 0.03) and higher patient global assessment (OR: 1.1, 95% CI: 1.0-1.2; P = 0.04) were associated with relapse. During the off-treatment phase, presence of CD19+ B cells (OR: 2.5, 95% CI: 1.2-5.1; P = 0.01) and reappearance of ANCA (OR: 3.2, 95% CI: 1.3-7.7; P = 0.01) were each associated with higher relapse risk. Multivariable analysis identified markers of inflammation (changes in platelets, white blood cells, and IgA) associated with relapse.
Conclusion:
Risk factors for relapse in AAV vary by treatment phase. Monitoring markers of inflammation and immune reconstitution may identify patients at risk for relapse, particularly after treatment withdrawal.
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