Efficacy of Leflunomide for Treatment of Vasculitis

NOURA MUSTAPHA ¹, Lillian Barra ², Simon Carette ³, David Cuthbertson ⁴, Nader A. Khalidi ⁵, Curry L. Koening ⁶, Carol Langford ⁷, Carol McAlear ⁸, Nataliya Milman ⁹, Larry Moreland ¹⁰, Paul Monach ¹¹, Philip Seo ¹², Ulrich Specks ¹³, Antoine Sreih ¹⁴, Steven Ytterberg ¹³, Peter Merkel ¹⁴, Christian Pagnoux¹⁵, CanVasc Canadian Vasculitis Research Network ¹⁶ and VCRC Vasculitis Clinical Research Consortium ⁸, ¹Hopital Notre Dame, Montreal, QC, Canada, ²St Joseph's health care, London, Canada, ³Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Canada, ⁴University of South Florida, Tampa, FL, ⁵McMaster University, Hamilton, ON, Canada, ⁶University of Utah Hospital, Salt Lake City, UT, ⁷Cleveland Clinic, Cleveland, OH, ⁸University of Pennsylvania, Division of Rheumatology, Philadelphia, ⁹Arthritis Centre at the Ottawa Hospital, Riverside Campus, Ottawa, Canada, ¹⁰University of Pittsburgh, PITTSBURGH, PA, ¹¹Brigham and Women's Hospital, Boston, MA, ¹²Johns Hopkins Medicine, Baltimore, MD, ¹³Mayo Clinic College of Medicine, Rochester, MN, ¹⁴University of Pennsylvania, Philadelphia, PA, ¹⁵Mount Sinai Hospital and University Health Network, Toronto, ON, Canada, ¹⁶Mount Sinai Hospital, Vasculitis clinic, toronto, ON, Canada

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, giant cell arteritis and large vessel vasculitis, treatment, Vasculitis

Session Information

Date: Monday, November 11, 2019

Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster III: Behçet’s Disease & Other Vasculitides

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Only a few small case series, case reports, and one small clinical trial suggested some benefit of leflunomide (LEF) in ANCA-associated vasculitis and other vasculitides. We analyzed the clinical efficacy and tolerability of LEF in a large cohort of patients with various vasculitides.

Methods: This was a retrospective analysis of patients who received LEF for treatment of their vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Study and in 3 additional centers from the Canadian vasculitis research network (CanVasc). Efficacy was defined as a response to LEF at 6 months after its initiation, as per the treating physician, with the ability to taper glucocorticoids (GC), if applicable, the relief of symptoms for which LEF was started, or the maintenance of remission without the need to add or substitute another agent. Efficacy was further analyzed at 12 and 24 months. The validation of efficacy also required the absence of active disease, corresponding to a Birmingham Vasculitis Activity Score of 0.

Results: Data for 93 patients were analyzed. As shown in Table 1, 45 patients had granulomatosis with polyangiitis (GPA), 8 microscopic polyangiitis (MPA), 12 eosinophilic granulomatosis with polyangiitis (EGPA), 14 giant-cell arteritis (GCA), 9 Takayasu’s arteritis (TAK) and 5 polyarteritis nodosa (PAN). The main reason for initiation of LEF was active disease (89%). The mean duration of treatment with LEF was 2.3±2.3 years; it was used with GC (mostly low-dose prednisone), at least initially, for 79% of patients; as monotherapy without GC for 18%; and in addition to another non-GC immunosuppressive sparing agent for 27%. As shown in Table 2, LEF was efficacious for remission induction or maintenance at 6 months for 62 (67%) patients (64% with GCA, 89% with TAK, 80% with PAN, 69% with GPA, 33% with EGPA); 20% discontinued LEF before achieving remission because of persistent disease activity. Five (5.4%) patients experienced nausea, vomiting, or diarrhea. Neuropathy was reported in 4, which resolved after cessation of LEF in 1 (3 had symptoms of minor sensory neuropathy and stopped LEF). Infections were reported in 4 patients (1 with GCA, also on GC, died from sepsis before month 6 of LEF) and mild transient elevation of transaminase levels in 3 patients. High blood pressure was reported in 1 patient after 12 months of use. Overall, 22 adverse events led to drug discontinuation in 18 (19%) patients, of which 6 stopped LEF before month 12 and before showing any benefit in 8/12 of these patients.

Conclusion: LEF can be an effective therapeutic option for various vasculitides, especially for non-severe refractory or relapsing ANCA-associated vasculitis or large-vessel vasculitis, and for maintenance in GPA or MPA. No new safety signals for LEF were identified in this population.

tab1

Table 1. Characteristics of patients who received leflunomide for treatment of vasculitis
-n = 93-.

tab2

Table 2. Response to treatment with leflunomide among patients with vasculitis

Disclosure: N. MUSTAPHA, granted by the Vasculitis program (University of Toronto) and the Royal College of Physicians of Canada., 2; L. Barra, None; S. Carette, None; D. Cuthbertson, None; N. Khalidi, None; C. Koening, None; C. Langford, Bristol-Myers Squibb, 2, GlaxoSmithKline,, 2, ChemoCentryx, 2, Genentech, 2, Bristol-Myers Squibb, 5, 9, Abbvie, 9, AstraZeneca, 9; C. McAlear, None; N. Milman, None; L. Moreland, None; P. Monach, None; P. Seo, None; U. Specks, None; A. Sreih, Bristol-Meyers Squibb, 3, Bristol-Myers Squibb, 3; S. Ytterberg, None; P. Merkel, Abbvie, 5, AbbVie, 5, AstraZeneca, 2, 5, AstraZeneca,, 2, 5, Biogen, 5, Boeringher-Ingelheim, 2, 5, Bristol-Myers Squibb, 2, 5, Celegene, 2, 5, Celgene, 2, 5, ChemoCentryx, 2, 5, CSL Behring, 5, Genentech/Roche, 2, 5, Genetech/Roche, 2, 5, Genzyme/Sanofi, 2, 5, GlaxoSmithKline, 2, 5, InflaRx, 5, Insmed, 5, Jannsen, 5, Kiniksa, 5, Kypha, 2, TerumoBCT, 2, UpToDate, 7; C. Pagnoux, ChemoCentryx, 5, Chemocentryx, 5, Genetech/Roche, 5, Genzyme/Sanofi, 5, GlaxoSmithKline, 5, Hoffman-La Roche, 2, 5, 8, Hoffman-LaRoche, 2, 5, 8, Sanofi, 5; C. Canadian Vasculitis Research Network, None; V. Vasculitis Clinical Research Consortium, None.

To cite this abstract in AMA style:

MUSTAPHA N, Barra L, Carette S, Cuthbertson D, Khalidi N, Koening C, Langford C, McAlear C, Milman N, Moreland L, Monach P, Seo P, Specks U, Sreih A, Ytterberg S, Merkel P, Pagnoux C, Canadian Vasculitis Research Network C, Vasculitis Clinical Research Consortium V. Efficacy of Leflunomide for Treatment of Vasculitis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/efficacy-of-leflunomide-for-treatment-of-vasculitis/. Accessed .

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