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.

Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: A pilot study.

OBJECTIVE: To report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV). METHODS: Belimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded. RESULTS: All patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients. CONCLUSION: Belimumab along with rituximab showed promising results in refractory patients with CV.

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.

Critical role of neutrophil extracellular traps (NETs) in patients with Behcet's disease.

OBJECTIVES: Behçet's disease (BD) is a chronic systemic vasculitis. Thrombosis is a frequent and life-threatening complication. The pathogenesis of BD is poorly understood and evidence supporting a role for primed neutrophils in BD-associated thrombotic risk is scant. To respond to inflammatory insults, neutrophils release web-like structures, known as neutrophil extracellular traps (NETs), which are prothrombotic. We evaluated the role of NETs and markers of NETs in BD. METHODS: Blood samples were collected from patients with BD, according to the International Study Group Criteria for Behçet's disease, and healthy donors (HD). NET components, including cell-free DNA (CfDNA) and neutrophil enzymes myeloperoxidase (MPO), were assessed in serum or in purified neutrophils from patients with BD and HD. RESULTS: Patients with active BD had elevated serum cfDNA levels and MPO-DNA complexes compared with patients with inactive BD and to HD. In addition, levels of cfDNA and MPO-DNA complexes were significantly higher in patients with BD with vascular involvement compared with those without vascular symptoms. Purified neutrophils from patients with BD exhibited spontaneous NETosis compared with HD. Thrombin generation in BD plasma was significantly increased and positively correlated with the levels of MPO-DNA complexes and cfDNA. Importantly, DNAse treatment significantly decreased thrombin generation in BD plasma but not in HD plasma. In addition, biopsy materials obtained from patients with BD showed NETs production in areas of vasculitic inflammation and thrombosis. CONCLUSIONS: Our data show that NETs and markers of NETS levels are elevated in patients with BD and contribute to the procoagulant state. Targeting NETs may represent a potential therapeutic target for the reduction or prevention of BD-associated thrombotic risk.

Large-vessel vasculitis in human immunodeficiency virus-infected patients.

OBJECTIVE: The objective of this study was to describe large-vessel vasculitis (LVV) in patients with human immunodeficiency virus (HIV) infection. It is a retrospective single-center study conducted between 2000 and 2015 through a university hospital of 11 HIV-infected patients with LVV. METHODS: The characteristics and outcome of 11 HIV-infected patients with LVV (7 patients fulfilled international criteria for Takayasu arteritis, 5 patients had histologic findings of vasculitis, and 5 patients had imaging features of aortitis) were analyzed and compared with those of 82 patients with LVV but without HIV infection. RESULTS: Concerning the HIV-infected patients with LVV (n = 11), the mean age was 40 years (range, 36-56 years), and 55% of patients were female. At diagnosis of LLV, the mean initial CD4 cell count was 455 cells/mm3 (range, 166-837 cells/mm3), and the median HIV viral load was 9241 copies. Vascular lesions were located in the aorta (n = 7), in supra-aortic trunks (n = 7), and in digestive arteries (n = 3). Inflammatory aorta infiltrates showed a strong expression of interferon-γ and interleukin 6. In HIV-negative LVV patients (n = 82), the median age was 42 years, and 88% of the patients were women. Thirty patients had an inflammatory syndrome. Seventy patients had been treated with glucocorticosteroids and 57 with immunosuppressive treatments. Compared with their negative counterparts, HIV-positive patients with LVV were more frequently male (P = .014), had more vascular complications (ie, Ishikawa score; P = .017), and had more frequent revascularization (P = .047). After a mean follow-up of 96 months, four relapses of vasculitis were reported, and one patient died. Regardless of the HIV virologic response, antiretroviral therapy improved LVV in only one case. CONCLUSIONS: LVV in HIV-infected patients is a rare and severe entity.

Ustekinumab for Behçet's disease.

OBJECTIVE: To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behçet's disease (BD). PATIENTS AND METHODS: Prospective study including 14 patients [median age of 39 (34; 41) years, with 71% of men] fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks. The primary efficacy endpoint was the proportion of patients with complete response (CR), defined as no oral ulcer, at week 12. RESULTS: At week 12, 64% were in CR, 21% in partial response and 14% non-responders. The median number of OU decreased from 2 [2; 4] to 1 [0; 1.25] (p = 0.0005) at week 12. Mean change from baseline to week 12 of Behçet's syndrome activity score (BSAS) was 22.8 ± 0.3 (p = 0.01). The median daily corticosteroids dose decreased from 12.5 (10; 16.3) to 5 [5; 10] mg/day (p = 0.02). Three patients reported headaches, leading to discontinuation of ustekinumab in one case. After a median follow-up of 7 [3; 12] months, 10 (71%) patients were still receiving ustekinumab and four (28%) experienced a relapse. Decreased levels of circulating IL-17 and IL-12 [median [IQR]; 3.9 [1.6; 10.6] vs. 29.2 [25.2; 42.7] pg/ml, and 29.4 [23.1; 33.3] vs. 56.1 [51.1; 64.4] pg/ml, p = 0.008 for both] were observed under ustekinumab, respectively. CONCLUSION: Ustekinumab seems to be efficient and safe for patient with BD and refractory OU although relapses are frequent.

Chronic hepatitis C virus infection, a new cardiovascular risk factor?

Among the large scope of extrahepatic manifestations related to hepatitis C virus (HCV) infection, many studies recently evaluated the frequency and characteristics of cardiovascular involvement. To assess the current published data on HCV infection and cardiovascular diseases. Published studies on cardiovascular disease, i.e. cerebrovascular accident and ischaemic heart disease in subjects with HCV infection were analysed from literature databases. Subjects with HCV chronic infection have an increased prevalence of carotid atherosclerosis and increased intima-media thickness compared to healthy controls or those with hepatitis B or non-alcoholic steatohepatitis. Active chronic HCV infection appears as an independent risk factor for ischaemic cerebrovascular accidents. Active chronic HCV infection is associated with increased risk of ischaemic heart disease. In some studies, successful interferon-based therapy showed a beneficial impact on the cardiovascular risk. The risk of major cardiovascular events is higher in patients with HCV infection compared to controls, independent of the severity of the liver disease or the common cardiovascular risk factors. The beneficial impact of interferon-based therapy needs to be confirmed with new direct antiviral interferon-free agents in prospective studies with extended follow-up.

Contribution of a heparin-binding haemagglutinin interferon-gamma release assay to the detection of Mycobacterium tuberculosis infection in HIV-infected patients: comparison with the tuberculin skin test and the QuantiFERON-TB Gold In-tube.

BACKGROUND: The screening and treatment of latent tuberculosis (TB) infection reduces the risk of progression to active disease and is currently recommended for HIV-infected patients. The aim of this study is to evaluate, in a low TB incidence setting, the potential contribution of an interferon-gamma release assay in response to the mycobacterial latency antigen Heparin-Binding Haemagglutinin (HBHA-IGRA), to the detection of Mycobacterium tuberculosis infection in HIV-infected patients. METHODS: Treatment-naïve HIV-infected adults were recruited from 4 Brussels-based hospitals. Subjects underwent screening for latent TB using the HBHA-IGRA in parallel to a classical method consisting of medical history, chest X-ray, tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-GIT). Prospective clinical and biological follow-up ensued, with repeated testing with HBHA-IGRA. A group of HIV-infected patients with clinical suspicion of active TB was also recruited and tested with the HBHA-IGRA. Multiplex analysis was performed on the culture supernatants of this in-house assay to identify test read-outs alternative to interferon-gamma that could increase the sensitivity of the test. RESULTS: Among 48 candidates enrolled for screening, 9 were identified with latent TB by TST and/or QFT-GIT results. Four of these 9 patients and an additional 3 screened positive with the HBHA-IGRA. This in-house assay identified all the patients that were positive for the TST and showed the best concordance with the presence of a M. tuberculosis exposure risk. During follow-up (median 14 months) no case of active TB was reported and HBHA-IGRA results remained globally constant. Fourteen HIV-infected patients with clinical suspicion of active TB were recruited. Active TB was confirmed for 6 of them among which 3 were HBHA-IGRA positive, each with very high interferon-gamma concentrations. All patients for whom active TB was finally excluded, including 2 non-tubercular mycobacterial infections, had negative HBHA-IGRA results. Multiplex analysis confirmed interferon-gamma as the best read-out. CONCLUSIONS: The HBHA-IGRA appears complementary to the QuantiFERON-TB Gold In-Tube for the screening of latent TB in HIV-infected patients. Large-scale studies are necessary to determine whether this combination offers sufficient sensitivity to dismiss TST, as suggested by our results. Furthermore, HBHA-IGRA may help in the diagnosis work-up of clinical suspicions of active TB.

Methotrexate versus conventional disease-modifying antirheumatic drugs in the treatment of non-anterior sarcoidosis-associated uveitis.

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.

Infliximab versus Cyclophosphamide for Severe Behçet's Syndrome.

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.).

Neutrophilic dermatosis and hidradenitis suppurativa in patients with Behçet's disease: A neutrophilic disease in the spectrum of autoinflammatory syndromes.

BACKGROUND: Association of neutrophilic dermatosis (ND), hidradenitis suppurativa (HS) and Behçet's disease (BD) and shared efficacy of TNFα axis blockade suggests common physiopathology. OBJECTIVES: To investigate the clinical features and therapeutic response of ND and HS associated with BD. METHODS: We identified 20 patients with ND or HS associated with BD among 1462 patients with BD. RESULTS: We analysed 20 (1.4%) patients diagnosed with ND or HS associated with BD: 13 HS, 6 pyoderma gangrenosum (PG), and 1 SAPHO. Our 6 PG cases over 1462 BD patients accounts for 400/100 000 prevalence. Thirteen had bipolar aphthosis, 6 vascular, 5 neurologic, and 4 ocular involvements. All PG occurred on limbs and had typical histology with constant dermal neutrophilic infiltrate. All HS had the classical axillary-mammary phenotype. Sixty-nine percent (69%) of HS were Hurley 1 stage. Treatment consisted mainly in colchicine (n = 20), glucocorticoids (n = 12), and anti-TNFα (n = 9). Interesting results with complete or partial responses were obtained with anti-TNFα (9 cases), ustekinumab (3 cases) and tocilizumab (1 case) to treat refractory ND or HS associated with BD. CONCLUSION: PG seems overrepresented in patients with BD. Biotherapies such as anti-TNFα, ustekinumab and tocilizumab appear to be promising to treat refractory ND or HS associated with BD.

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.

CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases.

Introduction: Autoimmune/inflammatory rheumatic diseases (AIRDs) patients might be at-risk of severe COVID-19. However, whether this is linked to the disease or to its treatment is difficult to determine. This study aimed to identify factors associated with occurrence of severe COVID-19 in AIRD patients and to evaluate whether having an AIRD was associated with increased risk of severe COVID-19 or death. Materials and methods: Two databases were analyzed: the EDS (Entrepôt des Données de Santé, Clinical Data Warehouse), including all patients followed in Paris university hospitals and the French multi-center COVID-19 cohort [French rheumatic and musculoskeletal diseases (RMD)]. First, in a combined analysis we compared patients with severe and non-severe COVID-19 to identify factors associated with severity. Then, we performed a propensity matched score case-control study within the EDS database to compare AIRD cases and non-AIRD controls. Results: Among 1,213 patients, 195 (16.1%) experienced severe COVID-19. In multivariate analysis, older age, interstitial lung disease (ILD), arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory diseases, and treatment with corticosteroids or rituximab were associated with increased risk of severe COVID-19. Among 35,741 COVID-19 patients in EDS, 316 having AIRDs were compared to 1,264 Propensity score-matched controls. AIRD patients had a higher risk of severe COVID-19 [aOR = 1.43 (1.08-1.87), p = 0.01] but analysis restricted to rheumatoid arthritis and spondyloarthritis found no increased risk of severe COVID-19 [aOR = 1.11 (0.68-1.81)]. Conclusion: In this multicenter study, we confirmed that AIRD patients treated with rituximab or corticosteroids and/or having vasculitis, auto-inflammatory disease, and sarcoidosis had increased risk of severe COVID-19. Also, AIRD patients had, overall, an increased risk of severe COVID-19 compares general population.

Prognosis Factors and Outcomes of Neuro-ophthalmologic Sarcoidosis.

BACKGROUND: Neuro-ophthalmologic manifestations are uncommon in sarcoidosis. We aim to assess the prognostic factors and outcome of neuro-ophthalmic sarcoidosis. METHODS: We conducted a multicenter retrospective study on patients with neuro-ophthalmic sarcoidosis. Response to therapy was based on visual acuity, visual field, and orbital MRI exam. Factors associated with remission and relapse were analyzed. RESULTS: Thirty-five patients [median (IQR) age of 37 years (26.5-53), 63% of women] were included. The diagnosis of sarcoidosis was concomitant of neuro-ophthalmologic symptoms in 63% of cases. Optic neuritis was the most common manifestation. All patients received corticosteroids and 34% had immunosuppressants. At 6 months, 61% improved, 30% were stable, and 9% worsened. Twenty percent of patients had severe visual deficiency at the end of follow-up. Nonresponders patients had significantly worse visual acuity at baseline (p = 0.01). Relapses were less frequent in patients with retro-bulbar optic neuropathy (p = 0.03). CONCLUSION: Prognosis of neuro-ophthalmic sarcoidosis is poor.

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.