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for the French Vasculitis Study Group and the European EGPA Study Group Objective. To describe the efficacy and safety of biologics for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). Methods. A retrospective European collaborative study was conducted in patients with EGPA who received treatment with biologics for refractory and/or relapsing disease. Results. Among the 147 patients with EGPA included in the study, 63 received rituximab (RTX), 51 received mepolizumab (MEPO), and 33 received omalizumab (OMA). At the time of inclusion, the median Birmingham Vasculitis Activity Score (BVAS) was 8.5 (interquartile range [IQR] 5-13) in the RTX group, while the median BVAS in the OMA group was 2 (IQR 1-4.5) and the median BVAS in the MEPO group was 2 (IQR 1-5). In patients receiving RTX, the median BVAS declined both at 6 months (median 1, IQR 0-4.5) and at 12 months (median 0, IQR 0-2), and the frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 49%, 24%, 24%, and 3%, respectively. For the treatment of glucocorticoid (GC)-dependent asthma, patients who received MEPO had a much better GC-sparing effect and overall response than did patients who received OMA. The frequency of remission, partial response, treatment failure, and stopping treatment due to adverse events was 15%, 33%, 48%, and 4%, respectively, in the OMA group and 78%, 10%, 8%, and 4%, respectively, in the MEPO group. Remission rates at 12 months were 76% and 82% among patients receiving MEPO at a doses of 100 mg and 300 mg, respectively. Conclusion. These results suggest that RTX could be effective in treating relapses of EGPA vasculitis. MEPO is highly effective with a good safety profile in patients with GC-dependent asthma. Our data suggest that 100 mg MEPO monthly could be an acceptable dosage for first-line therapy in selected instances of EGPA, recognizing, however, that this has not been compared to the validated dosage of 300 mg monthly.

Objectives To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). Methods A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. Results Forty-two patients with PAN received a total of 53 biological courses, including TNF-alpha blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases, and other biologics in 10 cases. TNF-alpha blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8–50) months, remission occurred in 40%, partial response in 13%, treatment failure in 40% and treatment discontinuation due to severe adverse events in 7% of patients receiving TNF-alpha blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients, respectively. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the 3 biologics, leading to early biologics discontinuation in only 3 cases. Conclusion These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

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 de...

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Background and Aims Glucocorticoids (GC) and/or immunosuppressive agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has been reported as a safe and effective option but only few data on renal outcome are available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy (cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional immunosuppressive regimens.2 We present the results of a multicentre cohort of patients with IgAV and cIgAN treated with RTX. Method The databases of 16 consorted European centres were investigated to screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in ≥25% glomeruli and rapid eGFR worsening at presentation), who received RTX as induction therapy. We selected patients with active renal manifestations at the time of RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or <5 if it was due to persistent proteinuria and relapse as an increase in BVAS requiring change in immunosuppressive therapy. Results We identified 38 patients with IgAV and 12 patients with cIgAN who received RTX and had active renal involvement at the time of treatment. The median age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of patients were male (Table 1). The median follow-up after RTX was 41 months (IQR 18-60). Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) had eGFR ≥60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%) achieved remission; after a median of 12 months (range 9-14), four experienced a minor relapse and one had a major relapse with significant renal disease progression. Renal function remained stable in all but two patients who developed end-stage renal disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last follow-up (p=0.029). Of the 26 patients with eGFR <60 mL/min/1.73 m2, 14 had IgAV and 12 had cIgAN. All were biopsied and 20 (77%) had diffuse endo/extra-capillary proliferation (classes IIIB-IV). Five patients required dialysis but recovered soon after treatment start. Remission was achieved by 16/26 (61%); eight (50%) subsequently relapsed and two (12%) reached ESRD. At last follow-up, eGFR was ≥60 mL/min/1.73 m2 in 8/26 (31%), 10/26 (48%) had stable renal function as compared to the time of RTX, while 8/26 (31%) had developed ESRD. Median 24h proteinuria decreased from 3400 mg (IQR 2150-6500) to 770 mg (177-1315) (p=0.016). Remission rate and ESRD-free survival were respectively 86% and 92% in patients with IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/24 (87%) patients who received RTX alone or combined to glucocorticoids but not to immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, only one patient reported a severe adverse effect related to RTX (pneumonia). Conclusion Renal involvement in adult-onset IgAV and cIgAN is frequently severe. RTX, combined or not with other immunosuppressive agents, may improve renal manifestations and is well tolerated. IgAV patients show higher remission rates and a longer ESRD-free survival as compared to cIgAN patients.

Background:Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis of medium- and small-sized arteries, not associated with antineutrophil cytoplasmic antibodies (ANCA). Conventional treatments include glucocorticoids (GCs) for non-severe disease and a combination of GCs and immunosuppressive agents for severe disease. Nevertheless, some patients have refractory and/or relapsing disease.Objectives:We examined the use of off-label biological therapy for relapsing/refractory PAN.Methods:This retrospective European collaborative study included patients with PAN meeting ACR criteria and/or Chapel Hill Consensus Conference 2012 definitions. Treatment efficacy and safety are recorded. Remission was defined as the absence of vasculitis manifestations (BVAS = 0) with a prednisone dose ≤5 mg/day. Partial response was defined as a BVAS = 0 with a prednisone dose between 6 and 10 mg/day.Results:Fifty-one patients (24 men, 27 women; median age 51 years) were included. Eighteen (35%) patients received TNF-alpha blockers, 16 (31%) received rituximab (RTX), 9 (18%) tocilizumab (TCZ), and 8 (16%) other biologics (including alemtuzumab in 3, anakinra in 2, interferon-alpha in 2 and abatacept in one). Previous treatments were: GCs in all cases, including methylprednisolone infusions (72%) and oral GCs (92%), cyclophosphamide (61%), azathioprine (53%), methotrexate (45%) and mycophenolate mofetil (47%). At inclusion, median BVAS was 5 (range 0-18), including 5 (2-12) in the TNF-alpha blockers group, 5 (2-12) in the RTX group and 4 (0-6) in the TCZ group.After median follow-up of 34.4 months (IQR 21.5-59.5), remissions, partial responses and treatment failure, respectively, were noted in 41%, 6% and 53% for TNF-alpha blockers recipients, 25%, 12% and 63% for RTX recipients, and 57%, 0% and 43% for TCZ recipients. No remission was noted in patients treated with anakinra, alemtuzumab and abatacept.Median BVAS dropped to 3 at 6 months, 0 at 12 months and 0 at last follow-up in the TNF-alpha blockers group, to 3.5, 0 and 2 in the RTX group, respectively, and 0, 0 and 0 in the TCZ group. A GC-sparing effect seemed more important with TNF-alpha blockers and TCZ. Median GCs dose decreased from the baseline 15 mg/day to 10 at 6 months, 5 at 12 months and 5 at last follow-up in the TNF-alpha blockers group, from 15 mg/day to 10 at 6 months, 5 at 12 months and 10 at last follow-up in the RTX group, and from 15 mg/day to 7 at 6 months, 5 at 12 months and 5 at last follow-up in the TCZ group.Four (22%) patients stopped TNF-alpha blockers because of allergic reaction in one and refractory disease in 3. Six (38%) stopped RTX because of refractory disease. Finally, 4 (44%) stopped TCZ because of adverse events in 2 (testicular abscess and worsening renal failure) and refractory disease in 2.Conclusion:The results of this study suggest that TNF-alpha blockers and TCZ may achieve higher rates of remission and GC-sparing in relapsing and/or refractory PAN than other biologics. Our data warrant further study to confirm or not these finding...

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