Intravenous Immunoglobulin As Immunomodulating Agent in ANCA-Associated Vasculitides: A French Nationwide Study of 92 Patients

Etienne Crickx¹, Irène Machelart², Estibaliz Lazaro³, Jean-Emmanuel Kahn⁴, Fleur Cohen⁵, Thierry Martin⁶, Alexandre Mania⁷, Pierre-Yves Hatron⁸, Gilles Hayem⁹, Claire Blanchard-Delaunay¹⁰, Claire De Moreuil¹¹, Guillaume Le Guenno¹², Frédéric Vandergheynst¹³, Francois Maurier¹⁴, Bruno Crestani¹⁵, Robin Dhote¹⁶, Nicolas Martin Silva¹⁷, Yann Ollivier¹⁸, Anas Mehdaoui¹⁹, Bertrand Godeau²⁰, Xavier Mariette²¹, Jacques Cadranel²², Pascal Cohen²³, Xavier Puéchal²³, Claire Le Jeunne²⁴, Luc Mouthon²⁵, Loïc Guillevin²⁶ and Benjamin Terrier²³, ¹Internal Medicine, Cochin Hospital, Paris, France, ²Hôpital Pellegrin, Pessac, France, ³Hôpital Haut-Lévêque, Pessac, France, ⁴Internal Medicine, Foch Hospital, Suresnes, France, ⁵Internal Medicine Dpt 2, Pitié-Salpêtrière Hospital, APHP, Paris, France, ⁶Cnrs UPR9021, IBMC, Strasbourg, France, ⁷Hôpital Gabriel Montpied, Clermont-Ferrand, France, ⁸Service de Médecine Interne, Centre National de Référence des Maladies Systémiques Rares, Hôpital Claude Huriez, CHRU Lille, Lille, France, ⁹Hôpital Ambroise Paré, Boulogne Billancourt, France, ¹⁰Internal Medicine, Centre Hospitalier, Niort, France, ¹¹CHU, Brest, France, ¹²Internal Medicine department, Clermont-Ferrand, France, ¹³Hôpital Erasme, Bruxelles, Belgium, ¹⁴HP Metz Belle Isle Hospital, Department of Internal Medicine, Metz, France, ¹⁵Pneumology, Bichat Claude-bernard, Universitary Hospital, APHP, Paris, France, ¹⁶Internal Medicine, Hospital Avicenne, Bobigny, France, ¹⁷CHU Caen, caen, France, ¹⁸Hôpital Cote de Nacre, Caen, France, ¹⁹Hôpital Eure Seine, Evreux, France, ²⁰Henri Mondor, Créteil, France, ²¹Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, Paris, France, ²²Hôpital Tenon, Paris, France, ²³Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Paris, France, ²⁴Department of Internal Medicine, Hotel-Dieu Hospital, AP-HP, Paris, Paris, France, ²⁵Department of Internal Medicine, Department of Internal Medicine, Cochin Hospital, Referent Center for Necrotizing Vasculitis and Systemic Sclerosis, Paris-Descartes University, AP-HP, Paris, France, ²⁶Internal Medicine, Hopital Cochin, Paris, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ANCA, intravenous immunoglobulin (IVIG) and vasculitis

Session Information

Date: Sunday, November 8, 2015

Title: Vasculitis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:

Despite recent therapeutic advances in treating ANCA-associated vasculitides (AAVs), some patients relapse or require long-term immunosuppression, leading to significant morbidity and mortality. IVIg represents a therapeutic alternative for AAVs, but its efficacy has been evaluated in only 2 small prospective trials. This study aimed to evaluate IVIg efficacy and safety for AAVs.

Methods:

We conducted a nationwide retrospective study (1990–2014) on patients with AAVs, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), who received IVIg immunomodulation (dose >1 g/kg/cycle). Patients given a substitution dose (<1 g/kg/cycle) for hypogammaglobulinemia were excluded.

Results:

Ninety-two patients (mean age: 51 years) with GPA (68%), EGPA (23%) or MPA (9%) received at least 1 IVIg cycle; 72% were ANCA-positive (immunofluorescence assay). IVIg were used as median 3^rd-line therapy (range: 1-8), for AAV relapse (83%), the first AAV flare (11%) or dependency on initiated treatments (6%).

The main clinical manifestations at IVIg onset were: ENT (61%), pulmonary (37%), constitutional symptoms (32%), arthralgias (28%), glomerulonephritis (20%), skin (16%), peripheral neuropathy (15%), central nervous system (13%), asthma (12%). The Five-Factor Score (FFS) was 0 (75%), 1 (21%) or 2 (4%). Mean BVAS was 9.4 (range: 0–34).

IVIg was given for a median of 6 (1–156) months (M), combined only with corticosteroids for 21% or with other immunosuppressants/another immunosuppressant for 77%.

IVIg efficacy was assessed for the whole population and a subset of 34 patients with unmodified background therapy; their respective remission rates at M3 and M6 were 49% and 62%, and 44% and 62%, with respective refractory disease rates of 23% and 25%.

Mean BVAS declined from 9.4±6.3 at baseline to 3.0±4.1 at M3, 2.3±4.5 at M6, 1.8±3.6 at M9 and 1.1±2.2 at M12. Similarly, mean CRP and mean prednisone dose also declined during the first year after starting IVIg.

Comparing patients achieving remission (n=43) versus those with only partial responses (n=24) or refractory disease (n=20) at M3, no significant differences were found for age, sex, AAV subtype, FFS, ANCA status or organ involvement at baseline, or IVIg-associated therapeutic regimens. Baseline BVAS was lower for patients who entered remission (7.6±6.8) versus those with partial responses (11.1±4.2, P=0.001) or treatment failures (10.9±6.1, P=0.017).

Adverse events occurred in 33%, among which 12% were serious and led to IVIg discontinuation for 7%.

Conclusion:

The results of this large study showed IVIg’s clinical benefit as adjunctive therapy, with an acceptable tolerance profile, supporting its use for patients with refractory or relapsing AAVs.

Disclosure: E. Crickx, None; I. Machelart, None; E. Lazaro, None; J. E. Kahn, None; F. Cohen, None; T. Martin, None; A. Mania, None; P. Y. Hatron, None; G. Hayem, None; C. Blanchard-Delaunay, None; C. De Moreuil, None; G. Le Guenno, None; F. Vandergheynst, None; F. Maurier, None; B. Crestani, None; R. Dhote, None; N. Martin Silva, None; Y. Ollivier, None; A. Mehdaoui, None; B. Godeau, None; X. Mariette, Biogen Idec, 2,Pfizer Inc, 2,Bristol-Myers Squibb, 5,Pfizer Inc, 5,AstraZeneca, 5,GlaxoSmithKline, 5; J. Cadranel, None; P. Cohen, None; X. Puéchal, None; C. Le Jeunne, None; L. Mouthon, None; L. Guillevin, None; B. Terrier, LFB, 5.

To cite this abstract in AMA style:

Crickx E, Machelart I, Lazaro E, Kahn JE, Cohen F, Martin T, Mania A, Hatron PY, Hayem G, Blanchard-Delaunay C, De Moreuil C, Le Guenno G, Vandergheynst F, Maurier F, Crestani B, Dhote R, Martin Silva N, Ollivier Y, Mehdaoui A, Godeau B, Mariette X, Cadranel J, Cohen P, Puéchal X, Le Jeunne C, Mouthon L, Guillevin L, Terrier B. Intravenous Immunoglobulin As Immunomodulating Agent in ANCA-Associated Vasculitides: A French Nationwide Study of 92 Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/intravenous-immunoglobulin-as-immunomodulating-agent-in-anca-associated-vasculitides-a-french-nationwide-study-of-92-patients/. Accessed .

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