A 2014 guidance statement published by the Executive Committee of the American Uveitis Society provided recommendations for the management of Behçet's disease in uveitis. Based on the available evidence, the expert panel recommends the use of anti-tumor-necrosis factor (anti-TNF) therapy, with infliximab or adalimumab, as a first- or second-line corticosteroid-sparing therapy for patients with ophthalmic manifestations of Behçet's disease. Infliximab may also be considered as a first- or second-line treatment for acute exacerbations of pre-existing Behçet's disease. The use of etanercept may be considered for Behçet's patients with uveitis who are intolerant to infliximab and adalimumab, although the quality of evidence is relatively lower. These recommendations are based on meta-analyses and comparative studies that have demonstrated the efficacy of anti-TNF agents, particularly infliximab, in managing the various manifestations of Behçet's disease. These studies have reported response rates exceeding 90% for patients with disease inadequately controlled by traditional immunomodulatory treatments. Infliximab has shown superior outcomes compared to conventional immunosuppressants, with significant reductions in disease exacerbations and improved visual acuity in patients with ocular involvement. [1]
According to 2018 European League Against Rheumatism (EULAR) guidelines for the management of Behcet’s syndrome, patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab, or interferon-alpha. This recommendation is primarily based on observational data that observed a rapid response and improvement in visual acuity with infliximab. Choice of treatment is recommended to depend on patient factors such as risk of infections, tolerability, physician’s experience, and reimbursement policies. Monoclonal anti-TNF antibodies should also be considered in patients with refractory venous thrombosis or arterial involvement of Behcet’s syndrome. For patients with severe and/or refractory gastrointestinal involvement, monoclonal anti-TNF antibodies and/or thalidomide should be considered. Similarly, monoclonal anti-TNF antibodies should be considered in severe nervous system involvement as first-line or in refractory patients. [2]
A 2024 systematic review and meta-analysis evaluated the long-term efficacy, safety, and cumulative retention rate of anti-TNF therapy in patients with Behçet's uveitis (BU). This meta-analysis included data from 12 clinical studies with a total of 1,156 patients diagnosed with BU, nine of which were retrospective and three prospective. Anti-TNF therapy achieved a pooled remission rate of ocular inflammation of 85.0% (95% confidence interval [CI] 78.7% to 90.5%) and visual acuity improvement in 77.4% of cases (95% CI 57.5% to 92.5%). Moreover, glucocorticoid dose reduction was significant, with a pooled decrease of 11.08 mg (95% CI -13.34 mg to -8.83 mg). The cumulative drug retention rate was determined to be 67.3% across studies, with subgroup analysis showing higher retention rates for adalimumab (70.3%) compared to infliximab (66.4%). Serious adverse events occurred in 5.8% of patients, with the most common being infusion or injection reactions (2.7%), tuberculosis (1.3%), and bacterial pneumonia (1.3%). Adalimumab exhibited a slightly higher ocular inflammation remission rate (89.3%) and lower incidence of severe infusion or injection reactions (2.2%) compared to infliximab (83.7% and 3.5%, respectively), which may reflect variations in immunogenicity and administration routes. Significant reductions in central macular thickness (CMT) were also observed, with a pooled decrease of 135.72 mcm in studies with follow-up of at least one year. Importantly, while the long-term safety profile of anti-TNF agents was favorable, the incidence of severe adverse events underscores the need for careful monitoring during treatment. [3]
A 2023 systematic review and meta-analysis evaluated the effectiveness of infliximab, a chimeric monoclonal anti-TNF antibody, for treating refractory central neuro-Behçet's disease. The analysis incorporated 21 studies conducted between 2000 and 2020, collectively involving 64 patients. Infliximab was administered in standard dosing regimens, commonly 5 mg/kg at weeks 0, 2, and 6, followed by maintenance dosing every 8 weeks. Across the pooled studies, 93.7% of patients exhibited a favorable response to therapy, defined as clinical improvement, stabilization or regression of radiographic findings, and biochemical normalization in cerebrospinal fluid (CSF) where available. Temporal trends suggested improved outcomes with earlier recognition and management of refractory central nervous system (CNS) involvement in Behçet's disease. Regression analysis confirmed that age, sex, or disease duration did not significantly confound treatment outcomes. Notably, infliximab displayed a steroid-sparing effect, with corticosteroid doses reduced or discontinued in several patients. Reported adverse events included mild hypersensitivity reactions, opportunistic infections, and headache, with few requiring discontinuation. These findings underscore infliximab as a highly effective treatment option for refractory neuro-Behçet's disease, although further validation in randomized controlled trials is warranted to address limitations in study design and reporting consistency. [4]
A 2022 meta-analysis and systematic review synthesized data from 13 single-arm cohort studies involving 739 patients with intestinal Behçet's disease to evaluate the efficacy and safety of anti-TNF agents, including infliximab and adalimumab. Study participants, predominantly from East Asia, had moderate to severe disease or were refractory to conventional therapies such as corticosteroids and immunomodulators. Pooled efficacy outcomes demonstrated clinical remission rates of 61%, 51%, 57%, and 38% at 3, 6, 12, and 24 months following treatment initiation, respectively. Endoscopic remission, a critical outcome indicating mucosal healing, was achieved in 66%, 82%, 65%, and 69% of patients at the same time points. Subgroup analysis showed comparable efficacy between infliximab and adalimumab, although moderate heterogeneity was noted across studies. Adverse drug reactions (ADRs) related to infliximab were reported in 22% of patients, with infusion reactions and infections being the most common events, occurring in 12% and 21% of cases, respectively. Adalimumab-associated ADRs were reported at rates of 30.7 and 28.7 events per 100 patient-years. Severe adverse events, including two cases of severe infection leading to hospitalization, were infrequent, and no deaths related to therapy were reported. These findings emphasize the promising role of anti-TNF agents as an effective therapeutic strategy for achieving remission and mucosal healing in patients with intestinal Behçet's disease, especially in those refractory to conventional treatments. However, limitations such as reliance on observational studies and heterogeneous follow-up protocols warrant further randomized controlled trials to establish definitive guidance. [5]
A 2022 single-center, retrospective study evaluated the efficacy of infliximab and adalimumab, two anti-TNF agents, in the management of refractory uveitis associated with Behçet's syndrome and sarcoidosis. The analysis included 131 patients: 68 in the infliximab group and 63 in the adalimumab group, treated between 2007 and 2019 at Tokyo Medical University Hospital. Infliximab was administered intravenously at a dose of 5 mg/kg at specified intervals, while adalimumab was delivered subcutaneously at a dose of 40 mg biweekly. The findings underscored significant visual acuity (VA) improvement (0.72 to 0.40 logMAR; p<0.001) in patients with Behçet's syndrome-related uveitis receiving infliximab, while adalimumab stabilized VA without significant change (0.42 to 0.36 logMAR; p= 0.11). Both agents significantly reduced CMT in eyes with uveitic macular edema (UME; 33 eyes in the infliximab group and 40 in the adalimumab group), with adalimumab showing greater efficacy in corticosteroid reduction for sarcoidosis patients. Infliximab achieved a complete discontinuation of corticosteroids in all treated patients, while adalimumab achieved a reduction or discontinuation in Behçet's syndrome and sarcoidosis to a lesser extent. Safety profiles revealed adverse events like infusion reactions in both groups, though adalimumab was associated with a higher overall frequency of adverse events (40.6% vs. 17.6%). The results suggest that while both agents are effective in controlling inflammation and UME in Behçet's syndrome, the pathogenesis of sarcoidosis may influence the comparative efficacy of adalimumab. [6]
A 2012 retrospective analysis evaluated the therapeutic impact of infliximab in seven patients presenting with severe vascular manifestations of Behçet's disease. The cohort consisted of five male and two female patients, with a mean age at diagnosis of 32.7 years. These patients exhibited significant vascular complications, including thoracoabdominal aortic dissection, retinal vasculitis, recurrent venous thromboses, and internal carotid artery dissection. Therapy with infliximab (3-5 mg/kg) was initiated as either a first-line intervention in three individuals or as an adjunct after failure of conventional immunosuppressive regimens in four patients. Existing immunosuppressive therapies included agents such as azathioprine, methotrexate, cyclosporine, and low-dose glucocorticoids. Treatment intervals with infliximab varied between four to eight weeks, tailored to disease severity and response. [7]
The analysis documented rapid suppression of inflammatory activity within 1-5 days of initiating infliximab therapy, evidenced by a decrease in mean C-reactive protein levels from 89 mg/L to 9 mg/L. Vascular stabilization was achieved, with grafts remaining patent and inflamed aortic walls demonstrating structural healing over six months. Notably, both patients with retinal vasculitis experienced significant visual improvement within two days of treatment initiation. Long-term outcomes included the cessation of infliximab in two patients after achieving sustained remission and the extension of infusion intervals in four additional cases. Concomitant immunosuppression regimens were well-tolerated, and no infliximab-related adverse effects were reported. These findings underscore the efficacy and safety of infliximab as a potential first-line therapeutic agent in the management of severe vascular complications associated with Behçet's disease. [7]
A 2019 prospective, large-scale, long-term postmarketing surveillance study (BRIGHT) evaluated the safety and efficacy of infliximab in 656 Japanese patients with refractory uveoretinitis in Behçet's disease (RUBD). The BRIGHT study encompassed a 24-month follow-up period and included patients who initiated infliximab therapy between January 2007 and January 2010. Infliximab was administered at a standard dose of 5 mg/kg body weight at weeks 0, 2, and 6, followed by maintenance infusions every eight weeks. The surveillance revealed that 32.32% of patients experienced ADRs, with infections being the most frequently reported (11.89%). Serious ADRs, such as tuberculosis and opportunistic infections, occurred in 6.10% of patients, particularly in those with comorbid respiratory or allergic conditions or concomitant glucocorticoid use. Efficacy findings demonstrated a sustained response, with 80.7% of participants achieving improvement or slight improvement by physician global assessment (PGA) at 24 months. Moreover, the median frequency of ocular attacks per six-month period dropped significantly from 2.0 at baseline to 0.0, while corrected VA was maintained throughout the study period. Additionally, the use of adjunctive therapies, including glucocorticoids and cyclosporine, decreased over time. These results underscore the tolerability and long-term efficacy of infliximab as a viable treatment option for RUBD in real-world clinical settings. [8]
A 2020 retrospective analysis examined the long-term efficacy and safety of infliximab monotherapy compared with combination therapies, including colchicine or corticosteroids, in patients with refractory uveitis due to Behçet's syndrome. The study evaluated 50 eyes of 27 patients, with detailed subgroup analyses involving 30 eyes treated with infliximab monotherapy and 20 eyes treated with combination therapies. The retention rate of infliximab exceeded 70% after 10 years, with no significant differences observed between monotherapy and combination approaches (p= 0.86). The frequency of ocular inflammatory attacks decreased from 4.2 episodes per year before treatment to 0.1 episodes per year by the sixth year, with no relapses observed after seven years of treatment. Best-corrected VA showed sustained improvement from a mean of 0.38 at baseline to 0.07 at the 10-year mark (p<0.001), indicating the treatment's long-term impact on preserving vision. The 10-year corticosteroid-sparing effect was substantial, with a mean daily dose reduction of 77.5% (from 11.1 mg to 2.5 mg). Adverse events, including infusion reactions and serious infections, were reported predominantly during the first five years of treatment; no adverse events occurred after the sixth year. Notably, the overall safety profile appeared consistent across both treatment modalities. The findings underscore that infliximab monotherapy is not inferior to combination therapy in terms of either efficacy or safety outcomes over a decade. These results provide robust evidence supporting infliximab as a critical option for the long-term management of refractory uveitis in Behçet's syndrome. [9]
A 2023 retrospective cohort analysis assessed the efficacy and safety of infliximab in vascular involvement among 127 patients with Behçet's syndrome over an 18-year span. Patients included in the cohort had various types of vascular involvement, including pulmonary artery thrombosis or aneurysms, non-pulmonary arterial lesions, extensive venous thrombosis, and venous ulcers. Nearly 87% of patients received infliximab for induction of remission, most of whom had been refractory to conventional immunosuppressive therapies such as azathioprine, cyclophosphamide, or mycophenolate mofetil. The remission rates at six and twelve months were assessed based on the absence of new or worsening vascular symptoms, CRP levels <10 mg/L, and stability or improvement of primary vascular lesions on imaging. [10]
The findings demonstrated remission rates of 73% at six months and 63% at twelve months across the cohort. Pulmonary artery involvement, accounting for 29% of cases, showed the most favorable response, with remission rates of 84% and 68% at six and twelve months, respectively, followed by venous thrombosis with rates of 82% and 70%. Conversely, patients with venous ulcers exhibited minimal improvement, with only 8% achieving remission at six months. During the mean follow-up period of 37 months, 50% of patients remained on infliximab, while adverse events, such as infusion reactions and serious infections, led to discontinuation in 11%. The relapse rate among those who achieved remission was remarkably low at 17%, highlighting infliximab's potential superiority for long-term maintenance in refractory vascular Behçet's syndrome, particularly in cases of pulmonary artery or severe venous involvement. [10]