Behçet's Disease 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.

Tocilizumab in Behçet Disease: A Multicenter Study of 30 Patients.

OBJECTIVE: To evaluate tocilizumab (TCZ) efficacy in patients with refractory Behçet disease (BD). METHODS: This is a multicenter study of 30 patients fulfilling the international criteria for BD and treated with TCZ at different European referral centers. The clinical response was evaluated at 6 months from TCZ initiation. RESULTS: Ninety percent of patients with BD were refractory or intolerant to anti-tumor necrosis factor (anti-TNF) agents. Overall, TCZ was effective in 25 (83%) patients with BD of whom 18 (60%) and 7 (23%) were complete and partial responders, respectively. The complete response was 67%, 60%, and 42% in patients with uveitis (18/30), neurological manifestations (5/30), and mucocutaneous and/or articular (7/30) manifestations, respectively. TCZ had a significant steroid-sparing effect allowing patients to decrease their median daily prednisone dose from 20 (IQR 10-40) mg/day to 9 (IQR 5-13) mg at 6 months (P < 0.001). The number of patients with BD needing concomitant disease-modifying antirheumatic drug therapy fell from 7 (23%) to 4 (13%) at 6 months. Mild to moderate side effects were observed in 6 (20%) patients, and 3 (10%) presented with serious adverse events (pneumonia, intestinal perforation, and septicemia) requiring therapy discontinuation in 2 cases. CONCLUSION: TCZ seems to be an effective alternative to anti-TNF agents in treating BD-related uveitis and neurological manifestations.

Lower Relapses Rate With Infliximab Versus Adalimumab in Sight-Threatening Uveitis: A Multicenter Study of 330 Patients.

PURPOSE: To compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA). DESIGN: Observational retrospective multicenter study. METHODS: A total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti-tumor necrosis factor [TNF]-α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients' medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety. RESULTS: Main etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti-TNF-α agents. CONCLUSIONS: In sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA.

Anti-Tumor Necrosis Factor α versus Tocilizumab in the Treatment of Refractory Uveitic Macular Edema: A Multicenter Study from the French Uveitis Network.

PURPOSE: To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME). DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both. METHODS: Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16]). MAIN OUTCOME MEASURES: Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months. RESULTS: Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients. CONCLUSIONS: Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents.

[Differences of characteristics and outcomes between cancer patients and patients with no active cancer hospitalised for a SARS-CoV-2 infection]. / Comparaison des caractéristiques et des pronostics des patients avec et sans cancer actif hospitalisés pour une infection à SARS-CoV-2.

BACKGROUND: Patients with solid cancer or haematologic malignancies have been considered to be more susceptible to SARS-CoV-2 infection and to more often develop severe complications. We aimed to compare the differences in clinical features and outcomes of COVID-19 patients with and without cancer. METHODS: This was a prospective observational cohort study of consecutive adult patients hospitalised in a COVID-19 unit at Pitié-Salpêtrière Hospital, Paris, France (NCT04320017). RESULTS: Among the 262 patients hospitalised in a medical ward during the pandemics with a confirmed COVID-19 diagnosis, 62 patients had cancer. Clinical presentation, comorbidities, and outcomes were similar between cancer and non-cancer patients. However, cancer patients were more likely to have been contaminated while being hospitalised. CONCLUSIONS: Oncologic and non-oncologic patients hospitalised for COVID-19 shared similar outcomes in terms of death, admission in intensive care, or thrombosis/bleeding. They should benefit from the same therapeutic strategy as the general population during the COVID-19 pandemic.

Biotherapies in Uveitis.

Non-infectious uveitis (NIU) represents one of the leading causes of blindness in developed countries. The therapeutic strategy aims to rapidly control intra-ocular inflammation, prevent irremediable ocular damage, allow corticosteroid sparing and save the vision, and has evolved over the last few years. Anterior NIU is mostly managed with topical treatment in adults. However, for intermediate, posterior and pan-uveitis, notably when both eyes are involved, systemic treatment is usually warranted. Biotherapies are recommended in case of inefficacy or non-tolerance of conventional immunosuppressive drugs in non-anterior NIU. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are by far the most widely used, especially adalimumab (ADA) and infliximab (IFX). In case of sight-threatening uveitis in Behçet's disease or in case of risk of severe recurrences, respectively IFX and ADA may be recommended as first-line therapy. Many questions are left unanswered; how long to treat NIU, how to discontinue anti-TNF-α agents, what biologic to use in case of anti-TNF-α failure? The objective of this review is to present an updated overview of knowledge on the use of biological treatments in NIU.

Development of a multivariate prediction model of intensive care unit transfer or death: A French prospective cohort study of hospitalized COVID-19 patients.

Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.

Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO's pharmacovigilance database.

PURPOSE: Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI). METHODS: Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as 'uveitis' at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-induced uveitis were differentially reported for each suspected treatment compared to the full database. We excluded drugs with potential indication bias. RESULTS: 1404 ICSRs corresponding to 37 drugs had a significant over-reporting signal with a median age of 57 [42-68] years and 45.7% of males. We identified five major groups of treatments: bisphosphonates (26.9%), non-antiviral anti-infectious drugs (25.4%), protein kinase inhibitors (15.5%), ICI (15.0%), and antiviral drugs (11.1%). Severe visual loss was reported in 12.1% of cases. ICI and protein kinase inhibitors were the most recently emerging signals. The time to onset between first infusion and uveitis was significantly different between groups ranging from 5 days [2-19] in the bisphosphonate group to 138.5 [47.25-263.75] in protein kinase inhibitors group (p < 0.0001). Anti-Programmed Cell death 1 represented more than 70% of ICI-induced uveitis. We identified Vogt-Koyanagi-Harada (VKH)-like syndrome as being associated with ICI use. CONCLUSIONS: The spectrum of drug-induced uveitis has changed with the evolution of pharmacopeia and the recent emergence of ICIs. VKH-like syndrome has been reported with ICI and protein kinase inhibitors therapy.