Anne-Claire Desbois’s research while affiliated with Unité Inserm U1077 and other places

Background: Cyclophosphamide and infliximab are recommended as induction therapies for severe Behçet's syndrome. Whether infliximab is safer and more effective than cyclophosphamide in treating severe Behçet's syndrome is not known. Methods: In this phase 2, Bayesian, multicenter randomized controlled trial, we assigned patients fulfilling the International Study Group's criteria for Behçet's syndrome who had major vascular or central nervous system involvement to receive either intravenous infliximab (5 mg/kg at weeks 0, 2, 6, 12, and 18) or cyclophosphamide (0.7 g/m2 intravenously at weeks 0, 4, 8, 12, 16, and 20, with a maximal dose of 1.2 g/infusion). All patients received the same glucocorticoid regimen. The primary outcome was complete response (clinical, biological, and radiological remission with a daily prednisone dose ≤0.1 mg/kg) at week 22. Results: Between May 2018 and April 2021, 52 patients with severe Behçet's syndrome (n=37 [71%] with vascular Behçet's syndrome and n=15 [29%] with neuro-Behçet's syndrome) were randomly assigned to receive either infliximab or cyclophosphamide. Complete response was achieved by 22 out of 27 (81%) and 14 out of 25 (56%) patients in the infliximab and cyclophosphamide treatment groups, respectively (estimated difference, 29.8 percentage points; 95% credible interval, 6.6 to 51.7). The posterior probability that at least 70% of treated individuals achieved complete response by week 22 was 97.4% for infliximab and 6.0% for cyclophosphamide. Overall, adverse events were recorded in 8 out of 27 (29.6%) patients receiving infliximab and 16 out of 25 (64%) patients receiving cyclophosphamide (estimated difference, -32.3 percentage points; 95% credible interval, -55.2 to -6.6). Serious adverse events were reported in 15% and 12% of patients receiving infliximab and cyclophosphamide, respectively. Conclusions: Among patients with severe Behçet's syndrome, induction therapy with infliximab had a superior complete response rate at 22 weeks and fewer adverse events than induction with cyclophosphamide. (Funded by the French Ministry of Health.).

Aims To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis. Methods Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation. Results 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 –not reached) vs 8.4 months (3.1–22.9) with MMF and 16.8 months (8.0–90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively. Conclusion In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile.

Background Behçet’s syndrome (BS) significantly increases morbidity and mortality, especially among patients with vascular (i.e. vascular-BS) and neurological involvement (i.e. neuro-BS). Cyclophosphamide and glucocorticoids have been for long the standard remission-induction therapy for severe BS, but disease flares require repeated treatment courses and lead to high cumulative doses. Current International guidelines advocate the combination of high-dose steroids with either cyclophosphamide or TNFi as induction therapy for severe Vascular- and Neuro-BS. Objectives We aimed to assess the efficacy and safety of infliximab and cyclophosphamide in severe BS. Methods In this phase 2, Bayesian, randomized, multicenter, controlled trial, we enrolled patients aged 12 years or older fulfilling the ISG criteria for BS and presenting major vascular or CNS involvement. They were randomly assigned to receive either intravenous Infliximab (5mg/kg at week 0, 2, 6, 12, and 18) or Cyclophosphamide (0.7-1.2 g/m² at week 0, 4, 8, 12, 16 and 20), combined with a standardized corticosteroid tapering regimen. Randomization was stratified by the main BS involvement at baseline (vascular or neurological involvement) and according to newly diagnosed or relapsing BS status. The primary outcome was a complete response at week 22, defined by resolution of all baseline vascular-BS or neuro-BS clinical manifestations, CRP level normalization and radiological remission under a prednisone dose ≤0.1mg/kg/day. Patients were analyzed in an intent-to-treat basis. Results Between May 2018 and April 2021, 52 patients with BS were enrolled; baseline characteristics are presented in Table 1 . Complete response was achieved by 22/27 (81%) and 14/25 (56%) patients in the infliximab and cyclophosphamide groups, respectively (estimated difference 22.9; credible interval 2.3 to 42.7). The posterior probability that the rate of complete response achieve at least 70% by week 22 was 97.4% for infliximab and 6.0% for cyclophosphamide ( Figure 1 ). By week 22, 17/19 (94%) and 10/18 (56%) vascular-BS patients achieved complete response in the infliximab and cyclophosphamide groups, respectively. For neuro-BS, 5/8 (71%) and 4/7 (57%) patients receiving infliximab and cyclophosphamide, respectively, achieved complete response. Relapse occurred in one (4%) and four (16%) patients receiving infliximab and cyclophosphamide, respectively. Forty-two mild-to-moderate adverse events (mainly infections) were recorded in 8/27 (29.6%) and 16/25 (64%) patients under infliximab and cyclophosphamide, respectively. Serious adverse events were similar between groups. Conclusion Among patients with severe BS, induction therapy with infliximab had better complete remission rate at 22 weeks and a safer profile as opposed to cyclophosphamide.View this table: • View inline • View popup Table 1. Baseline characteristics of patients within the ITAC trial • Download figure • Open in new tab • Download powerpoint Figure 1. Posterior probability of the difference in complete response rates at Week 22 The posterior probabilities with a prior (Beta (7,3)) are provided. REFERENCES NIL Acknowledgements We thank Dr Delphine Leclercq, Dr Marine Bravetti, and Dr Alessandra Bartoli (Pitié - Salpétrière Hospital) for composing the Endpoint Adjudication Committee. We also thank all the patients who participated, and their relatives; the staff involved in caring for trial participants at all trial sites, and Cendrine Chaffaut and Nabil Raked for their involvement in the data monitoring and the statistical analysis. Disclosure of Interests None declared

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

Uveitis in Behçet’s disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior, or panuveitis. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralization usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10–15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, the prevention of recurrent attacks, the achievement of complete remission, and the preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update to a previous article by our team on pathogenesis, diagnostic approaches, and the therapeutic strategy of BD uveitis.

Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20-30%) and more rarely peripheral neuropathy (approximately 10-15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse.