Date: Sunday, October 21, 2018
Session Title: 3S090 ACR Abstract: Vasculitis–ANCA-Assocd (904–909)
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: The deregulated overproduction of interleukin (IL)-6 has been implicated in several inflammatory and antibody-mediated autoimmune diseases. We aimed to investigate serum IL-6 levels (sIL-6) during active disease, remission, and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with repopulation of blood B cells and disease relapse.
Methods: sIL-6 levels were measured longitudinally over 18 months in 78 patients with AAV enrolled in a prospective, double-blinded, randomized, control trial comparing treatment with rituximab (RTX) (n=45) or cyclophosphamide (CYC)/azathioprine (AZA) (n=33). Outcome variables included baseline clinical features, ANCA type and titers, disease activity (status of active disease versus complete remission (CR)), time to B cell repopulation, relapse and severe relapse.
Results: Baseline sIL6 levels were detectable (>0.49pg/ml) in 81% of patients. At baseline, sIL-6 positively correlated with levels of proteinase (PR3)-ANCA (rs=0.36, p<0.01), but not with levels of myeloperoxidase (MPO)-ANCA levels (rs=-0.17, p=0.47). Higher baseline sIL-6 levels were associated with the presence of fever, pulmonary nodules/cavities, PR3-ANCA, conductive deafness and absence of urinary red blood cell casts (p<0.05 for all comparisons).
The median sIL-6 level was higher at baseline and promptly declined with induction therapy at following time-points (baseline, median [25%-75% IQR], 2.66 [0.76-20.98]; month 6th, 0.49 [0.49-1.16]; p<0.01) in a similar fashion in both treatment arms.
An increase in sIL-6, but not CRP, during clinical remission was a predictor for subsequent severe relapse in RTX-treated patients (Hazard Ratio (HR) 7.24, p=0.01), but not in CYC/AZA-treated patients (HR 0.62, p=0.50). In RTX-treated B cell depleted patients (CD19+ B cell/microliter <10), the rise of sIL-6 levels did not precede B cell reappearance, regardless of whether a cut-off of≥10 CD19+B cell/microliter (HR=0.97; p=0.97) or of≥69 CD19+B cell/microliter (HR=1.50; p=0.41) was considered.
Eighty percent of the patients who subsequently had a severe relapse in the RTX arm had B cell redetection before or at the time of the IL-6 increase, whereas, of the RTX-treated patients who did not have a severe relapse, 79% had B cell redetection but only 21% of those had B cell redetection before or at the same time of the sIL6 increase.
Conclusion: At baseline, sIL-6 correlates with PR3-ANCA titers and associates with specific clinical manifestations of AAV. A rise in sIL-6 levels, but not CRP levels, after complete remission is associated with subsequent severe relapse in RTX-treated patients. The observed discrepancies between treatments deserve confirmation and further study.
To cite this abstract in AMA style:Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B, Langford C, Hoffman GS, Kallenberg CGM, Seo P, Spiera RF, St. Clair EW, Fervenza F, Stone JH, Monach PA, Specks U, Merkel PA. Serum Interleukin-6 Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/serum-interleukin-6-levels-in-antineutrophil-cytoplasmic-antibody-associated-vasculitis/. Accessed January 21, 2020.
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