Search

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome, is a small-vessel necrotizing vasculitis associated with eosinophilia and asthma. Glucocorticoids (GCs) usually control the disease, but relapses and GC-dependant asthma are frequent, leading to potential biological therapy use. Objectives: We examined off-label biological therapy use for relapsing/refractory EGPA. Methods: Remission was defined as the absence of asthma and vasculitis manifestations with a prednisone dose ≤5 mg/day, and partial response as the absence of manifestations requiring prednisone dose between 6 and 10 mg/day. Results: One hundred and eigteen patients (66 men, 52 women; median age 50.5 years) were included. Fifty (42%) patients received rituximab (RTX), 38 (32%) mepolizumab (MEPO), and 30 (26%) omalizumab (OMA). Previous treatments were: oral GCs (98%), methylprednisolone infusions (51%), azathioprine (68%), cyclophosphamide (47%), methotrexate (30%), mycophenolate mofetil (8%). At inclusion, median (interquartile range) BVAS in the RTX, OMA and MEPO groups were 8 (4.5-13), 2 (1.5-4) and 2 (2-5), respectively, median (IQR) daily GCs dose were 20 mg/day (15-40), 20 mg/day (10-37.5), 10 mg/day (7.5-20). GC-dependant asthma was found in 39 (78%) of the RTX group, 36 (95%) in the MEPO group and 28 (93%) in the OMA group. After median follow-up of 22.8 months (IQR 10-47), remissions, partial responses and therapeutic failures, respectively, were noted in 50%, 16% and 34% for RTX recipients, 17%, 38% and 45% for the OMA group and 84%, 3% and 13% for the MEPO group. Median BVAS dropped to 0 at 6 and 12 months and at last follow-up in all groups. A GC-sparing effect seemed more important with RTX and MEPO. Median GCs dose decreased from the baseline 20 mg/day to 8.5 at 6 months, 7.5 at 12 months and 5 at last follow-up in the RTX group, from 20 mg/day to 12 at 6 months, 10 at 12 months and 10 at last follow-up in the OMA group, and from 10 mg/day to 5 at 6 months, 3 at 12 months and 5 at last follow-up in the MEPO group. In the MEPO group, no difference was noted between patients receiving 100 mg and those 300 mg monthly.Nine (18%) patients stopped RTX because of refractory disease, and 12 (24%) experienced adverse events, including severe infections in 5. Thirteen (43%) stopped OMA because of severe infusion reaction in one and refractory disease in 12, and 4 (13%) patients receiving OMA experienced adverse events. Three (8%) patients stopped MEPO because of adverse events in 2 (one severe infusion reaction and one because of paresthesia), because of pregnancy in one. Seven (18%) additional patients receiving MEPO experienced adverse events, mainly asthenia. Conclusion: The results suggest that RTX may be effective in 50% of patients with vasculitis relapses related to EGPA, with an acceptable safety profile, while MEPO is highly effective with a good GCs-sparing effect and safety profile in patients with steroid-dependant asthma. Disclosure of Interests: Alice Canzian: None declared, Nils Venhoff: None declared, Silvia Sartorelli: None declared, Anne Marie Ruppert: None declared, Matthieu Groh: None declared, Camille Taille: None declared, Virginie Rieu: None declared, Perrine Smets: None declared, Francois Maurier: None declared, Nicolas Girszyn: None declared, Maxime Samson: None declared, Claire De Moreuil: None declared, Gregory Pugnet: None declared, Xavier Delbrel: None declared, Jean-Emmanuel Kahn: None declared, Xavier Puechal: None declared, Giacomo Emmi: None declared, Loic Guillevin: None declared, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Jens Thiel: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

Background Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss) is a small-vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Glucocorticoids (GCs) control the disease, but GC-dependence is frequent. Evolving concepts distinguish vasculitis-related symptoms from asthma and/or ENT manifestations. That distinction has become even more important since the development of B-cell and eosinophil-targeted therapies. Objectives This study aimed to describe and identify characteristics predicting long-term EGPA outcomes. Methods We set up a multicenter European cohort that included 636 EGPA patients. Based on recent consensus, we distinguished 4 EGPA-evolutionary profiles: GC-dependent asthma and/or ENT manifestations (requiring prednisone >7.5 mg/d), ≥1 vasculitis relapse(s) (excluding asthma and/or ENT flares), both phenotypes, and complete remission (no GC-dependent asthma/ENT signs, no vasculitis relapse and prednisone Results After median follow-up of 63 (IQR 30-110) months, 35.8% had GC-dependent asthma and/or ENT manifestations, 12.9% had ≥1 vasculitis relapse(s), 14.3% had both phenotypes, 14.6% were in complete remission, 14.4% were in partial remission and 7.8% had not reach remission. Patients with GC-dependent asthma/ENT manifestations were younger at diagnosis (p Patients with vasculitis relapse(s) had more frequently neurological manifestations at diagnosis (p=0.002) and MPO-ANCA positivity (p Finally, patients in complete remission were older (p Conclusion EGPA seems to evolve toward distinct phenotypic profiles, which could be identified using baseline and follow-up characteristics. Early identification of those profiles could allow guided choices of the best therapeutic option. Disclosure of Interests Matthias Papo: None declared, Renato A. Sinico: None declared, Vitor Teixeira: None declared, Maria-Letizia Urban: None declared, Juliane Mahrhold: None declared, Sara Monti: None declared, Giulia Cassone: None declared, Franco Schiavon: None declared, Benjamin Seeliger: None declared, Thomas Neumann: None declared, Claus Kroegel: None declared, Matthieu Groh: None declared, Chiara Marvisi: None declared, Maxime Samson: None declared, Thomas Barba: None declared, David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda, Bernhard Hellmich Consultant for: Roche, Speakers bureau: Abbvie, MSD, Roche, Novartis, Pfizer, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Jean-Emmanuel Kahn: None declared, Bernard Bonnotte: None declared, Cecile-Audrey Durel: None declared, Luc Mouthon: None declared, Xavier Puechal: None declared, Loic Guillevin: None declared, Giacomo Emmi: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

Background Giant cell arteritis (GCA) is a large-vessel vasculitis affecting elderly people, and most frequently women (sex-ratio of 2.3). Some studies suggest an increased risk of malignancies in GCA. Objectives We aimed to describe the clinical, paraclinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a control group without malignancy. Methods Patients with a diagnosis of GCA and of solid neoplasm or malignant blood disease, within one year before or after the diagnosis of vasculitis, were included. A random group of age-matched (3:1) control patients from our monocentric inception cohort of GCA patients from Caen University Hospital was constituted. Results Twenty-four observations were collected (median age 75.5 years). All fulfilled ≥3/5 ACR criteria. Temporal artery biopsy was positive in 17 cases (70.8%). There were 1 active (4.2%) and 9 former (37.5%) smokers. Only 1 patient had a previous prostate cancer. Malignancies were 10 malignant blood diseases (41.7%, 3 chronic lymphoid leukemias, 3 essential thrombocythemias, 1 myeloma, 1 chronic myelomonocytic leukemia, 1 MALT lymphoma, 1 Waldenstrom9s macroglobulinemia) and 14 solid neoplasms (58.3%, 3 lung, 3 breast, 2 prostate, 1 thyroid, 1 colon, 1 pleural cancers, 1 melanoma, 1 Kaposi9s sarcoma and 1 Merkel cell carcinoma). Malignancy was diagnosed at a median of 1 month after GCA diagnosis in 21 patients and before in the other 3. Diagnosis of malignancy was made in consultation in 5 patients (3 skin cancers and 2 breast cancers), on lab tests in 13 (thrombocytosis, anemia or increased prostate specific antigen) and on imaging in 6. Treatments of malignancy included chemotherapy alone in 8 patients (33.3%), simple monitoring in 6 patients (25%), surgery alone in 4 patients (16.7%), surgery and radiotherapy and/or chemotherapy in 4 patients (16.7%), decrease of corticosteroids in 1 patient, and 1 patient was lost to follow-up. Two patients (8.3%) died from infectious complications, 8 patients (33.3%) had a GCA relapse, including one with concomitant malignancy relapse. After a median follow-up of 16 months [0–134], 5 patients (20.8%) were weaned from steroids, all considered in malignancy remission. Seven patients (29.1%) were still under chemotherapy, 9 patients (37.5%) were considered to be in malignancy remission. There were more males in patients with concomitant malignancy, compared to the control group (respectively 15/24 and 21/72, p Conclusions Our study shows an over-representation of male gender in GCA with concomitant malignancy. Vasculitis outcomes were not influenced by the malignancy treatment. The diversity of malignancies encountered in this study raises the issue of an incidental association. Initial clinical and paraclinical follow-up dictated by vasculitis may have led to an early identification of associated malignancy, and thus represent a lead time bias. Disclosure of Interest None declared