ANCA-Negative and Myeloperoxidase-ANCA-Positive Patients with Granulomatosis with Polyangiitis: Clinical Manifestations and Risk of Relapse

Eli Miloslavsky¹, Na Lu², Sebastian Unizony³, Hyon K. Choi³, Peter A. Merkel⁴, Philip Seo⁵, Robert F. Spiera⁶, Carol A. Langford⁷, Gary S. Hoffman⁷, Cees Kallenberg⁸, E. William St.Clair⁹, Nadia Tchao¹⁰, Fernando Fervenza¹¹, Paul A. Monach¹², Ulrich Specks¹³ and John H. Stone¹⁴, ¹Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, ²Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ³Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁴Penn Vasculitis Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, ⁵Division of Rheumatology, Johns Hopkins, Baltimore, MD, ⁶Rheumatology, Hospital for Special Surgery, New York, NY, ⁷Rheumatology, Cleveland Clinic, Cleveland, OH, ⁸Rheumatology/Clin Immunol AA21, Univer Med Center Groningen, Groningen, Netherlands, ⁹Rheumatology and Immunology, Duke University, Durham, NC, ¹⁰ITN, San Francisco, CA, ¹¹Mayo Clinic, Rochester, MN, ¹²Rheumatology, Boston University School of Medicine, Boston, MA, ¹³Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN, ¹⁴Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston, MA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ANCA, myeloperoxidase (MPO) and vasculitis, Wegener's granulomatosis

Session Information

Date: Sunday, November 8, 2015

Title: Vasculitis I

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Recent studies in ANCA-associated vasculitis (AAV) have suggested that classification based on ANCA type (PR3 versus MPO) may represent a more clinically relevant division than the traditional disease type categorization (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). The differences between these two classifications are driven primarily by patients with GPA who are MPO-ANCA+ or ANCA-negative. However, little scrutiny of these patient subsets has been described in the literature. We analyzed the clinical features and treatment outcomes of MPO-ANCA+ patients with GPA and ANCA-negative patients with GPA enrolled in the Wegener’s Granlomatosis Etanercept Trial (WGET) or the Rituximab in AAV (RAVE) trial.

Methods:

We performed a pooled analysis of patients enrolled in the WGET and RAVE trials. We compared both MPO-ANCA+ and ANCA-negative patients with GPA to two well-defined AAV subgroups: 1) PR3-ANCA+ patients with GPA and, 2) MPO-ANCA+ patients with MPA.

Results:

Among the 365 patients analyzed, 273 had PR3-ANCA+ GPA (75%), 33 had MPO-ANCA+ GPA (9%), 15 had ANCA-negative GPA (4%) and 44 had MPO-ANCA+ MPA (12%).

MPO-ANCA+ patients with GPA

MPO-ANCA+ patients with GPA were more often female than PR3-ANCA+ patients with GPA and were younger than MPO-ANCA+ patients with MPA (Table 1). The clinical features and frequency of granulomatous inflammation confirmed by histopathology were similar between MPO-ANCA+ GPA and PR3-ANCA+ patients with GPA. However, MPO-ANCA+ patients with GPA showed a complete absence of scleritis and endobronchial lesions though these differences did not reach significance. MPO-ANCA+ patients with GPA also differed from MPO-ANCA+ patients with MPA in having more frequent manifestations typically associated with GPA. The rate of relapsing disease at trial entry and relapse rate during the trial in patients with MPO-ANCA+ GPA was similar to that of PR3-ANCA+ GPA but higher than MPO-ANCA+ patients with MPA.

ANCA-negative patients with GPA

ANCA-negative patients with GPA were similar in age and sex distribution to PR3-ANCA+ patients with GPA but had lower BVAS/WG scores at trial entry (4.5 vs 7.7, p<0.01). Renal involvement was less frequent, while granulomatous features on histology and relapsing disease at trial entry were more frequent in ANCA-negative patients with GPA than their PR3-ANCA+ GPA counterparts.

Conclusion:

In this population of patients enrolled in clinical therapeutic trials of AAV, MPO-ANCA+ patients with GPA did not differ significantly from PR3-ANCA+ patients with GPA with respect to clinical manifestations or rate of relapse. ANCA-negative patients with GPA had more frequent relapsing disease at study entry than PR3-ANCA+ patients with GPA. This data adds to the debate on the contribution of ANCA type and disease type to clinical manifestations and treatment outcomes in AAV.

Disclosure: E. Miloslavsky, Genentech Inc., 2; N. Lu, None; S. Unizony, None; H. K. Choi, None; P. A. Merkel, None; P. Seo, None; R. F. Spiera, None; C. A. Langford, None; G. S. Hoffman, None; C. Kallenberg, None; E. W. St.Clair, Biogen Idec, 2; N. Tchao, None; F. Fervenza, None; P. A. Monach, None; U. Specks, None; J. H. Stone, Roche, Genentech, 2,Genentech, 5.

To cite this abstract in AMA style:

Miloslavsky E, Lu N, Unizony S, Choi HK, Merkel PA, Seo P, Spiera RF, Langford CA, Hoffman GS, Kallenberg C, St.Clair EW, Tchao N, Fervenza F, Monach PA, Specks U, Stone JH. ANCA-Negative and Myeloperoxidase-ANCA-Positive Patients with Granulomatosis with Polyangiitis: Clinical Manifestations and Risk of Relapse [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/anca-negative-and-myeloperoxidase-anca-positive-patients-with-granulomatosis-with-polyangiitis-clinical-manifestations-and-risk-of-relapse/. Accessed .

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