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Recent advances in the diagnosis and management of Behçet’s syndrome uveitis
Expert Review of Ophthalmology
... This can lead to better overall disease control, improved quality of life, and a reduced risk of long-term complications. [11][12][13][14][15] A paramount concern when employing any form of immunosuppressive therapy, including the treatment of Behçet's syndrome, is the potential for heightened susceptibility to infections. Immunosuppression, by its very nature, involves dampening the body's immune response, which is the intricate defense system responsible for recognizing and eliminating harmful pathogens such as bacteria, viruses, and fungi. ...
Background: Behçet's syndrome (BS) is a chronic inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. Immunosuppressants and biologics are commonly used to manage BS, but their comparative efficacy and safety remain unclear. Methods: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library databases from January 2013 to October 2024. Randomized controlled trials (RCTs) comparing immunosuppressants (azathioprine) and biologics (TNF-alpha inhibitors - infliximab, adalimumab, etanercept) in adult BS patients were included. The primary outcomes were clinical response rates (defined as improvement in disease activity scores) and adverse events. A random-effects model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Six RCTs (n=785 patients) met the inclusion criteria. Biologics demonstrated significantly higher clinical response rates compared to immunosuppressants (OR 4.57, 95% CI 3.26-6.40, p<0.00001). Infliximab, adalimumab, and etanercept showed superiority over azathioprine (OR 4.40, 95% CI 2.33-8.30, p<0.00001; OR 5.51, 95% CI 2.86-10.61, p<0.00001; OR 4.19, 95% CI 2.54-6.92, p<0.00001, respectively). Adverse events were comparable between groups, with no significant difference in serious infections or malignancies. Conclusion: Biologics, particularly TNF-alpha inhibitors, are more efficacious than conventional immunosuppressants in inducing clinical response in BS, with similar safety profiles. These findings support the use of biologics as a first-line treatment option for moderate-to-severe BS.
We aimed to highlight disease-related and treatment-related complications of Behçet syndrome (BS) based on previous and recent studies and our own experience.
The Behçet’s Disease Overall Damage Index is a newly developed instrument to assess damage in BS. Validation studies showed that damage is already present in some patients at diagnosis and continues to progress during the follow-up, mainly related to treatment complications. Nervous system and eye involvement are important causes of long-term disability. Cyclophosphamide seems to be associated with infertility and an increased risk of malignancies among BS patients, prompting the consideration of shortening the treatment duration. Flares in mucocutaneous manifestations have been reported with tocilizumab, and de novo BS manifestations with secukinumab therapy.
Earlier diagnosis and treatment are essential to prevent disease-related damage in BS. Treatment-related complications seem to be the leading cause of damage during the disease course.
Purpose
This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain.
Methods
A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events.
Results
Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected.
Conclusion
The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain.
Experience with mycophenolate in uveitis due to Behçet syndrome (BS) is limited. Twelve patients with panuveitis or posterior uveitis who were started mycophenolate were included. Data on demographic characteristics, therapies, ocular attacks, and adverse events were extracted from patient charts. Seven patients with BS uveitis were prescribed mycophenolate for remission induction, of which 6 were refractory/intolerant to conventional immunosuppressives. Mycophenolate was combined with anti-TNFs in 3 patients, resulting in no further ocular attacks. Mycophenolate had to be stopped in the fourth patient due to adverse events. The remaining 3 patients continued to have ocular attacks and were switched to other agents without any drop in visual acuity. Among the 5 patients who were prescribed mycophenolate for maintenance, 2 were relapse free, but 3 experienced ocular attacks. One patient had an exacerbation of mucocutaneous lesions, and 2 experienced adverse events. Mycophenolate monotherapy may not be adequate for remission induction of refractory BS uveitis, but it can be a safe and effective alternative when combined with a biologic agent. It may also be an option for maintenance therapy.
Behçet's uveitis (BU), a vision-threatening manifestation of Behçet's disease, poses substantial management challenges due to its chronic, relapsing nature and potential for vision loss. This review explores the role of biologic therapies in the treatment of BU, providing a comprehensive overview of their effectiveness, drawbacks, and future possibilities. Traditionally, management has relied heavily on corticosteroids and conventional immunosuppressants. However, their long-term use is frequently associated with systemic side effects and insufficient control of ocular inflammation. Biologic therapies, particularly TNF-alpha inhibitors like infliximab and adalimumab, have emerged as effective alternatives, offering better disease control and a more favorable safety profile. We critically evaluated these agents, noting their clinical efficacy in reducing inflammatory flares and preserving visual acuity. Despite their benefits, several issues remain. Accessibility, cost, and lack of long-term safety data limit their widespread use. Additionally, individual variability in treatment response necessitates personalized therapeutic strategies. Recent research has shown promise in addressing these challenges, with the emergence of novel biologic agents and personalized medicine approaches. In summary, biologic therapies represent a paradigm shift in BU management, contributing to better patient outcomes. Yet, there are significant challenges to be overcome. As we move forward, continued research, development of novel biologic agents, and a precision medicine approach will shape the future landscape of BU treatment.
Behçet's uveitis (BU) is a debilitating manifestation of Behçet's disease, often requiring prompt and aggressive treatment to prevent vision loss. Glucocorticoids (GCS) serve as a first-line therapy for BU; however, their long-term, high-dose use can result in significant adverse effects. This review summarizes the efficacy, adverse effects, and advances in combination therapy involving GCS for the management of BU. We discuss the benefits and drawbacks of various GCS administration routes, including periocular and intravitreal injections, intravitreal sustained-release devices, and systemic therapy, highlighting the role of fluocinolone acetonide and dexamethasone as primary sustained-release formulations. Moreover, we underscore the importance of combining GCS with immunosuppressive drugs and biological agents to minimize adverse reactions and optimize therapeutic outcomes. The review concludes that, while GCS remain a crucial component of BU treatment, careful consideration of their administration and combination with other therapies is essential to achieve long-term remission and improved visual outcomes for patients with BU.
Uveitis is a type of ocular inflammatory disease caused by various etiologies, for which corticosteroids are the main treatment. Dexamethasone Intravitreal implant (DEX-I) has been widely used in the treatment of uveitis across the world. Then, new indications and complications appeared. This review aims to summarize the use of DEX-I in uveitis in the past 10 years.
We summarized the clinical data (baseline characteristics, efficacy and safety) and discussed controversies by retrospectively analyzing the articles and cases published in PubMed and Web of Science using the terms “Ozurdex”, OR “intravitreal dexamethasone implant”, AND “uveitis” from 2010 to 2022.
DEX-I is effective in reducing edema, improving inflammation and improving vision when treating various conditions of uveitis including infectious, no-infectious, pediatric uveitis, and surgery-related applications. The efficacy of DEX-I as a monotherapy is related to the following: etiology and course of disease, treatment of systemic diseases, patients’ toleration after multiple injections, economic situation, etc. In addition, intravitreal corticosteroids implantation may replace systemic therapy in some patients. In terms of safety, the incidence of high intraocular pressure is about 20.52%, and the incidence of cataract is about 15.51%.
DEX-I can effectively treat non-infectious uveitis and some infectious uveitis such as suspected tuberculosis, and its safety is controllable. Further studies are necessary to evaluate the effect of monotherapy and to expand more indications.
Purpose
To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi.
Methods
A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation.
Results
In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: − 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 μm, difference 53.57 μm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference − 1.92; 95% CI: − 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted.
Conclusion
We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity.
Objectives
To evaluate long-term outcomes of infliximab (IFX) treatment in patients with Behçet's disease (BD)-associated uveitis.Patients and methodsWe retrospectively analyzed the cases of patients with BD-associated uveitis treated with IFX for > 5 years. We compared the numbers of ocular inflammatory attacks, ocular disease activities, and visual acuity before and after the initiation of IFX treatment.ResultsThe 24 patients were 20 men and 4 women. Their mean age at the initiation of IFX treatment was 37.3 ± 9.2 years. The mean term from the initiation of IFX treatment was 10.3 ± 2.4 years. The average number of ocular inflammatory attacks was 5.4 ± 2.1 per 12 months before the IFX treatment and significantly lower at 0.83 ± 0.96 per 12 months after the initiation of IFX treatment (p < 0.05). We used a scoring system for BD-associated uveitis named the Behçet's disease ocular attack score 24 (BOS24) to estimate the changes in ocular disease activities between before and after initiation of IFX treatment. The average score decreased significantly from 7.58 ± 2.77 to 2.55 ± 2.74 after the initiation of IFX treatment (p < 0.05). Even after > 5 years of the treatment, both the number of ocular attacks and the BOS24 score kept decreasing. The visual acuity in 42 of 48 eyes (24 patients) was improved or maintained.ConclusionsIFX was effective for controlling ocular inflammatory attacks and diminishing ocular disease activities in patients with BD-associated uveitis, and it maintained the patients' visual acuity.
Background:
Bechet's disease (BD), a chronic multiorgan involving disease, has a significant impact on quality of life in spite of effective treatment modalities. Disease manifestations such as arthritis, orogenital ulcerations, rashes, angiitis, and neurological involvement affect health-related quality of life (HRQoL) through its impact on depression, anxiety, and fatigue.
Objectives:
We aimed explore the psychological impact of BD, taking into consideration the effect on the HRQoL, as well as the association with depression, anxiety, wellbeing, and fatigue.
Methods:
This is a narrative review of the literature that looks into the association of BD on the HRQoL including all studies that have assessed such as association.
Results/findings:
Depression and anxiety are prevalent among patients with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship.
Conclusion:
Depression and anxiety are strongly associated with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship. Besides, the controlling factors of the psychological impact are still to be deciphered.
Objectives:
To evaluate the effect of vision-related quality of life on depression and anxiety in patients with Behçet uveitis.
Materials and methods:
The Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI) I-II, and the Visual Functioning Questionnaire (VFQ)-25 were used to evaluate 105 patients being followed for Behçet uveitis. Sociodemographic data and VFQ-25 scores were compared between the groups with and without depression and anxiety. Regression analysis was performed to determine the relationship between the variables.
Results:
Forty-eight (82.8%) men and 10 (17.2%) women who completed the questionnaires were included in the study. The mean age of the patients was 37.76±11.14 (18-65) years and the mean duration of uveitis was 8.57±7.43 (1-27) years. The mean VFQ-25 composite, BDI, STAI-I, and STAI-II scores were 74.90±18.50 (18.79-97.04), 10.76±8.90 (0-43), 42.52±6.23 (25-55), and 46.53±6.80 (27-58), respectively. Of 58 patients, 31% had depressive symptoms and 58.6% had anxiety symptoms. VFQ-25 composite score was lower in the depressive group than in the group with no depression (p=0.030), while there was no significant difference in this score between the groups with and without anxiety. Regression analysis revealed a negative relationship between total VFQ-25 composite score and depression.
Conclusion:
In our study, high rates of depression and anxiety were detected in patients with Behçet uveitis. Patient-reported visual functioning was associated with depression. In patients with Behçet uveitis, it is important to evaluate vision-related quality of life as well as visual acuity.
Behçet’s disease is a systemic vasculitis that affects multiple organs. The most common manifestations are oral and genital ulcerations and recurrent uveitis. Uveitis can be an initial symptom in 10–20% of cases and leads to blindness in 16–25% of patients. The management of this disease is evolving due to the clinical phenotypes recently described in the literature and increasing focus on the detection of subclinical inflammation to enable correct therapeutic decisions. The first line treatment is azathioprine, followed by various immunosuppressive and biological agents as alternatives in severe or refractory cases. This review summarizes scientific articles about the etiology of, diagnostic tools for and treatment of the ocular manifestations of Behçet’s disease available in the PubMed database from 1 January 2016 to 1 May 2021. A multidisciplinary approach is necessary to effectively prevent permanent damage and thus improve the life quality of the patients. Therefore, it is crucial to raise awareness of the common clusters of symptoms, use of modern imaging methods, such as ocular computed tomography and fluorescein angiography, and novelty treatment algorithms to enable early diagnosis and appropriate management.
Purpose
To provide a comprehensive review of rituximab use for the treatment of non-infectious uveitis and scleritis.
Methods
Review of literature through December 2020.
Results
Individual data was available for 229 patients with refractory non-infectious uveitis (n = 108) or scleritis (n = 121) who received treatment with rituximab (RTX). Rituximab was generally utilized as third-line or later treatment (uveitis: 67/90, 74.4%; scleritis: 90/96, 93.8%) at a mean of 33.5 months following the diagnosis of uveitis (range = 0 to 168.0 months; median = 24.0 months) and 39.4 months after diagnosis of scleritis (range = 1.0 to 168.0 months; median = 21.0 months). Patients with non-infectious uveitis and scleritis either received prior treatment with corticosteroids only (uveitis: 18/90, 20%; scleritis: 4/94, 4.3%), or with one (uveitis: 19/90, 21.1%; scleritis: 30/94, 31.9%), two (uveitis: 11/90, 12.2%; scleritis 27/94, 28.7%), or three or more (uveitis: 37/90, 41.1%; scleritis: 31/94, 33.0%) corticosteroid-sparing immunosuppressive agents with or without corticosteroids before initiation of RTX treatment. The rheumatologic protocol (two infusions of 1 gram of RTX separated by 14 days) was utilized most frequently (uveitis: 45/87, 51.7%; scleritis: 87/114, 76.3%), followed by the Foster protocol (eight weekly infusions of 375 mg/m² RTX; uveitis: 18/87, 20.7%; scleritis: 10/114, 8.8%), and the oncologic protocol (four weekly infusions of 375 mg/m² RTX; uveitis: 5/87, 5.7%; scleritis: 6/114, 5.3%). Various other off-label regimens were used infrequently (uveitis: 19/87, 21.8%; scleritis 11/114, 9.6%). Rituximab treatments resulted in a positive therapeutic response for the majority of patients with non-infectious uveitis (81/97, 83.5%). Commonly treated uveitic diagnoses included non-paraneoplastic autoimmune retinopathy (30/107, 28.0%), juvenile idiopathic arthritis (21/107, 19.6%), Vogt-Koyanagi-Harada disease (12/107, 11.2%), and Behçet disease (11/107, 10.3%). Cases of non-infectious scleritis were most commonly attributed to granulomatosis with polyangiitis (75/121, 62.0%) and rheumatoid arthritis (15/121, 12.4%), and showed an even greater rate of positive therapeutic response (112/120, 93.3%) following RTX treatment. No side effects were reported in 76.3% (74/97) of uveitis and 85.5% (71/83) scleritis cases. Of those cases associated with RTX-induced adverse events, the most common were infusion reactions of various severity (11/35, 31.4%).
Conclusions
Overall, RTX appeared to be both effective and well-tolerated as second or third-line therapy for patients with non-infectious uveitis and scleritis.
Behçet’s disease (BD) is a systemic vasculitis disease of unknown origin occurring in young people, which can be venous, arterial or both, classically occlusive. Ocular involvement is particularly frequent and severe; vascular occlusion secondary to retinal vasculitis may lead to rapid and severe loss of vision. Biologics have transformed the management of intraocular inflammation. However, the diagnosis of BD is still a major challenge. In the absence of a reliable biological marker, diagnosis is based on clinical diagnostic criteria and may be delayed after the appearance of the onset sign. However, therapeutic management of BD needs to be introduced early in order to control inflammation, to preserve visual function and to limit irreversible structural damage. The aim of this review is to provide current data on how innovations in clinical evaluation, investigations and treatments were able to improve the prognosis of uveitis associated with BD.
Long-acting, slow-release injectable fluocinolone intravitreal implants have been approved for the treatment of non-infectious uveitis affecting the posterior segment. We summarise the development of intravitreal fluocinolone implants and discuss the technology including pharmacokinetics. We conducted a systematic review of evidence for the efficacy, safety and patient acceptability of fluocinolone 0.18 mg and 0.19 mg injectable implants. We summarise evidence from the pivotal phase 3 studies that lead to the approval of these implants and evaluate real-world including disease-specific evidence. Safety including injection-related events and long-term adverse events is presented.
Purpose
To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU).
Methods
Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control).
Results
Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed.
Conclusion
Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.
Behçet’s disease (BD) is a systemic variable vessel vasculitis that involves the skin, mucosa, joints, eyes, arteries, veins, nervous system and gastrointestinal system, presenting with remissions and exacerbations. It is a multifactorial disease, and several triggering factors including oral cavity infections and viruses may induce inflammatory attacks in genetically susceptible individuals. BD vasculitis involves different vessel types and sizes of the vascular tree with mixed-cellular perivascular infiltrates and is often complicated by recurrent thrombosis, particularly in the venous compartment. Several new therapeutic modalities with different mechanisms of action have been studied in patients with BD. A substantial amount of new data have been published on the management of BD, especially with biologics, over the last years. These important therapeutic advances in BD have led us to propose French recommendations for the management of Behçet’s disease [Protocole National de Diagnostic et de Soins de la maladie de Behçet (PNDS)]. These recommendations are divided into two parts: (1) the diagnostic process and initial assessment; (2) the therapeutic management. Thirty key points summarize the essence of the recommendations. We highlighted the main differential diagnosis of BD according to the type of clinical involvement; the role of genetics is also discussed, and we indicate the clinical presentations that must lead to the search for a genetic cause.
Purpose
To evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU).
Design
Open-label, prospective multicentre safety study.
Participants
Thirty-eight subjects with NIU, with and without macular oedema (MO).
Methods
Treatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations.
Main outcome measures
The main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST).
Results
Based on a CST of ≥300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; two of which were deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was <1 ng/mL. Efficacy parameters showed improvement over the 24-week study period.
Conclusions
Suprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.
Objective
An unmet need exists for reliable, validated, and widely‐accepted outcome measures for randomized clinical trials in Behçet's syndrome. The Outcome Measures in Rheumatology (OMERACT) Behçet's Syndrome Working Group, a large, multidisciplinary group of experts in Behçet's syndrome and patients with Behçet's syndrome, had an objective of developing a core set of data‐driven outcome measures for use in all clinical trials of Behçet's syndrome.
Methods
The core domain set was developed through a comprehensive, iterative, multistage project that included a systematic review, a focus group meeting and qualitative patient interviews, a survey among experts in Behçet's syndrome, a Delphi exercise involving both patients and physician experts in Behçet's syndrome, and use of the data, insight, and feedback generated by these processes to develop a final core domain set.
Results
All steps were completed and domains were delineated across the organ systems involved in this disease. Since trials in Behçet's syndrome often focus on specific manifestations and not on the disease in its entirety, the final proposed core set includes 5 domains mandatory for study in all trials in Behçet's syndrome (disease activity, new organ involvement, quality of life, adverse events, and death) with additional subdomains mandatory for study of specific organ–systems. The final core set was endorsed at the 2018 OMERACT meeting.
Conclusion
The core set of domains in Behçet's syndrome provides the foundation through which the international research community, including clinical investigators, patients, the biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective therapies.
Purpose
To evaluate the clinical course of patients with Behçet uveitis after discontinuation of infliximab (IFX) therapy.
Methods
Medical records of eight patients who discontinued treatment between 2010 and 2018 were retrospectively analyzed. The main outcome measures were frequency of uveitis attacks per year, best-corrected visual acuity (BCVA), aqueous flare, foveal thickness and fluorescein angiography (FA) scores before initiation, during treatment and after 6, 12, and 24 months of cessation of the IFX therapy.
Results
The mean follow-up after withdrawal of infusions was 38.6 ± 20.4 (12–90) months. Frequency of uveitis attacks, BCVA, aqueous flare, foveal thickness and FA scores were improved significantly after treatment (p < .05). In terms of these parameters, there was no significant difference between the periods of during treatment and after 6, 12, and 24 months of cessation of the IFX therapy.
Conclusion
IFX therapy might be discontinued safely with an effective inflammation control in patients with Behçet uveitis.
Behçet’s disease is a multi-organ inflammatory disorder with systemic vasculitis of unknown etiology. Ocular lesions occur in about 70% of patients with Behçet’s disease, and it is more frequent and severe in men. The frequency of ocular inflammatory attacks has been used as a main outcome measure to assess the efficacy of therapy on uveoretinitis in patients with Behçet’s disease. The ocular Behçet’s disease research group of Japan have recently proposed a new scoring system, Behçet’s disease ocular attack score 24 (BOS24), to assess the disease activity of ocular Behçet’s disease. This review highlights the efficacy and application of the BOS24 scoring system in clinical practice for patients with ocular Behçet’s disease. In addition, a new semi-quantitative scoring system to evaluate the degree of retinal vascular leakage on fluorescein angiography reported by our group is described.
Objectives:
To investigate the changes over time in extraocular and ocular manifestations of Behçet's disease (BD) in Tunisian patients.
Material and methods:
Retrospective study of 246 patients divided into two groups: group 1 (147 patients examined from 1995 to 2005) and group 2 (99 patients examined from 2006 to 2017).
Results:
Active or scarred genital ulcers observed by physician at presentation were significantly less frequent in group 2 (47.2% vs. 29.6%; p = 0.007), as were articular involvement (50.3% vs. 34.7%; p = 0.016) and erythema nodosum (18.4% vs. 8.1%; p = 0.024). One hundred-seven patients (43.5%) developed ocular manifestations during the 23-year study period. Intermediate uveitis was significantly more frequent in group 2 than in group 1 (11.7% vs. 28.4%; p = 0.003), and posterior uveitis less frequent in group 2 than in group 1 (34.2% vs. 19.7%; p = 0.016). Patients from group 2 were more likely to have macular edema (19.8% vs. 45.6%; p = 0.001). However, better visual prognosis, with a lower rate of legal blindness, was noted in group 2.
Conclusions:
Changes over time included a decrease in the rate of articular involvement and cutaneous involvement. There was an increase in the rate of intermediate uveitis and a decrease in the rate of posterior uveitis over time. Despite an increase in the rate of macular edema, there was an improvement in visual prognosis, with less legal blindness over time.
Objective
To examine the 36-month efficacy and safety of a 0.2 μg/day fluocinolone acetonide insert (FAi) to treat noninfectious intermediate, posterior, or panuveitis (NIU-PS).
Design
Phase 3, prospective, double-masked, multicenter study (clinicaltrials.gov, NCT01694186).
Subjects
Adults (≥18 years old) with a diagnosis of NIU-PS in ≥1 eye for ≥1 year and ≥2 recurrences of uveitis requiring systemic corticosteroid, immunosuppressive treatment, or intraocular corticosteroids.
Methods
Participants were randomized 2:1 to FAi or sham (injection plus standard of care) treatment.
Main Outcome Measures
The primary outcome was the difference between the proportion of FAi-treated and sham-treated patients who had a uveitis recurrence. Secondary outcomes included time to first recurrence, number of recurrences, best corrected visual acuity (BCVA) change from baseline, resolution of macular edema, and number of adjunctive treatments.
Results
129 participants (n=87 FAi-treated; n=42 sham-treated) were enrolled. Over 36 months of treatment, cumulative uveitis recurrences were significantly reduced with FAi compared with sham (65.5% vs. 97.6%, respectively; P<0.001); time to first recurrence was commensurately longer (median 657.0 and 70.5 days, respectively; P<0.001). The number of recurrences per eye was significantly lower in the FAi- compared with sham-treated group (mean 1.7 vs. 5.3, respectively, P<0.001). At 36 months, more FAi-treated eyes had a ≥15-letter increase in BCVA from baseline and fewer FAi-treated eyes had investigator-determined macular edema at Month 36, compared with sham-treated eyes (33.3% vs. 14.7% and 13.0% vs. 27.3% for BCVA and macular edema, respectively). Fewer FAi-compared with sham-treated participants required adjunctive treatments (57.5% vs. 97.6%, respectively). Intraocular pressure (IOP) was similar for both study groups at Month 36 (mean ± standard deviation 14.5±5.1 and 14.8±5.3, respectively), and approximately half as many eyes in the FAi-treated group when compared with the sham-treated group underwent IOP-lowering surgery (5.7% vs. 11.9%). Cataract surgery was required more frequently over 36 months in the FAi- compared with the sham-treated group (73.8% vs. 23.8% of eyes, respectively).
Conclusions
FAi-treated eyes had significantly reduced uveitis recurrence rates throughout the study duration, significantly increased recurrence-free durations, fewer recurrence episodes among those with recurrences, less adjunctive therapy, and an acceptable side-effect profile compared with sham-treated eyes.
ABSTRACT
Purpose: To assess factors that impact the risk of relapse in patients with non-infectious uveítis (NIU) who undergo adalimumab tapering after achieving remission.
Design: Retrospective study.
Methods:
- Setting: Multicenter study.
- Study Population: Patients with NIU treated with adalimumab and subsequently tapered.
- Observation Procedure: Patient demographics, type of NIU, onset and duration of disease, period of inactivity before tapering adalimumab and tapering Schedule were collected.
- Main Outcome Measures: Independent predictors of the rate of uveitis recurrence after adalimumab tapering.
Results: 328 patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2±70.1 weeks.
Adalimumab tapering was commenced after a mean of 100.8±69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7±61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs. 37.5 years, p=0.0005) and the rate of recurrence was significantly higher in younger subjects (HR=0.88 per decade of increasing age, p=0.01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR=1.23 per unit increase in speed, p<0.0005). Conversely, a more extended period of remission prior to tapering was associated with a lower rate of recurrence (HR=0.97 per 10-weeks longer period of inactivity, p=0.04).
Conclusions: When tapering adalimumab, factors that should be considered include patient’s age, race, and duration of disease remission on adalimumab. A slow tapering Schedule is advisable.
Objectives
To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD).
Methods
An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member.
Results
Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15–30 mg of prednisolone or equivalent for >2–4 weeks.
Conclusions
These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
Purpose of review:
Uveitis is a major manifestation of Behçet disease (BD) and potentially has a high morbidity. This article reviews recently published data on BD uveitis.
Recent findings:
A set of classification criteria and a diagnostic algorithm have been developed for BD uveitis. Recent reports have confirmed male predominance and posterior segment inflammation in the majority of BD uveitis patients. A high uveitis attack severity score, fluorescein angiographic leakage at the posterior pole, and disruption of outer retinal layers on optical coherence tomography (OCT) predict poor visual outcome. OCT-angiography studies have suggested subclinical changes of retinal capillaries in patients with or without ocular involvement. In a randomized controlled trial, interferon-α was superior to cyclosporine. Favorable outcomes were reported with earlier initiation, optimization, and withdrawal of infliximab after remission. Adalimumab as first-line was superior to conventional therapy.
Summary:
Classification criteria will be used to select a homogeneous group of patients for research and the diagnostic algorithm may help ophthalmologists predict the probability of BD uveitis based on ocular findings. Fluorescein angiography and OCT are the routine imaging modalities. Clinical relevance of OCT-angiography is unclear. Interferon-α, infliximab, and adalimumab have proven superior efficacy compared to conventional therapy.
Objectives:
The assessment of quality of life (QoL) in Behçet's disease (BD) patients has been a surrogate of disease outcomes, but a wider impact on the patient's lifestyle has not been considered. This systematic review aims to provide an overview of the existing tools specifically adopted to explore the QoL in BD patients.
Methods:
A systematic literature review was conducted using 2 electronic databases, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A combination of BD and QoL-related search terms were used. All articles were screened by 3 independent reviewers for title, abstract and full text level. Studies investigating QoL in BD patients were included.
Results:
64 papers of 497 records were retained. Data about 7,449 patients with a BD diagnosis and QoL evaluation were collected. 47 different tools to evaluate QoL were detected. The mean number of tools adopted in each study was 2.14±1.34. General QoL and psychological and social impact were investigated in 68.75% and 54.69% respectively. The correlation with disease activity was investigated in 71.86%.
Conclusions:
The assessment of QoL in BD patients may provide a fundamental measurement for health to evaluate the outcome of interventions for BD patients. The adoption of a single validated QoL tool, developed including the BD patient's perspective, may provide an accurate and effective assessment, ensure the comparison within different cohorts, and set standardised values to define QoL level in BD patients.
Objective
To compare the risk of blindness and vision-threatening ocular comorbidities in patients with Behçet’s disease (BD) vs the general population.
Methods
Using 2002–2017 Korea National Health Insurance Service database, we did a population-based cohort study comparing newly-diagnosed BD patients and age- and sex-matched non-BD controls at a 1:5 ratio. The primary outcome was blindness defined as a best-corrected visual acuity of ≤ 20/500 in the better-seeing eye. Secondary outcomes were vision-threatening ocular comorbidities (cataract, glaucoma, and retinal disorders) that require surgical interventions and incident uveitis. Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). We performed subgroup analyses by sex and BD diagnosis age.
Results
We included 31 228 BD patients and 156 140 controls. During a follow-up of 9.39 years, the incidence rate of blindness per 1000 person-years was 0.24 in BD and 0.02 in controls with the HR [95% CI] of 10.73 [7.10–16.22]. The HR [95% CI] for secondary outcomes was 2.06 [1.98–2.15] for cataract surgery, 5.43 [4.57–6.45] for glaucoma surgery, and 2.71 [2.39–3.07] for retinal surgery. The HR [95% CI] of incident uveitis was 6.19 [5.83–6.58]. Males suffered a disproportionately higher risk of blindness than females due to greater severity than lower incidence of uveitis. The risk of uveitis and blindness decreased as BD diagnosis ages increased.
Conclusion
In this large population-based cohort study, BD patients compared with the general population have a 10.73-fold risk of blindness in 10-years and also a substantially higher risk of diverse ocular comorbidities that pose potential threats to vision.
Purpose: To evaluate the effectiveness and reasons for discontinuation including the side effect profiles of adalimumab in a real-world setting.
Design: A retrospective clinical cohort study was performed.
Methods: Setting: Medical chart review of clinical practice in two tertiary eye care services in Rotterdam, the Netherlands. Data were collected from 1 May 2004, through 1 September 2020.
Study population: Patients with non-infectious uveitis treated with adalimumab (n = 341; 633 affected eyes) were included.
Main outcome measure(s): The primary outcome was the effectiveness of adalimumab, measured by the number of patients achieving inactive disease, remission and relapse free survival. The secondary outcomes were the reasons for discontinuation including side effects and the number of patients that developed antibodies.
Results. In total, 341 patients were treated with adalimumab between May 2004 and September 2020. The uveitis recurrence-free survival interval was 3.4 years (range 0-13 years). Adalimumab had an acceptable side-effect profile. 178 patients achieved inactive disease while continuing adalimumab, and 51 patients maintained remission after discontinuing adalimumab. Reasons for discontinuation of adalimumab were no response, relapse, or reasons unrelated to the effectiveness of treatment. Adalimumab antibodies were present in 40/115 patients (35%). Antibodies were associated with lower adalimumab levels and antibodies were observed more often in patients on adalimumab monotherapy (P <0.01).
Conclusion: Adalimumab is effective for patients with non-infectious uveitis, with an acceptable side-effect profile. Though relapses can occur, the majority of the patients achieved inactive disease or remission after cessation of adalimumab without other systemic immunosuppressive medication.
Introduction
Behçet's disease (BD) is an auto-inflammatory disease, primarily characterized by recurrent painful mucocutaneous ulcerations.
Methods
A literature search was performed to write a narrative review into the pathogenesis and current treatment options of BD.
Results
The pathogenesis of BD remains to be elucidated, but is considered a genetically primed disease in which an external trigger causes immune activation resulting in inflammatory symptoms.
GWAS data show an association between multiple genetic polymorphisms (HLA-B51, ERAP1, IL10 and IL23R-IL12RB2) and increased susceptibility to BD. Bacteria as streptococci, an unbalanced microbiome or molecular mimicry trigger the inflammation in BD. Increased production or responsiveness of pro-inflammatory components of the innate immune response (TLR, neutrophils, NK-cells or γδ T-cells) to these triggers may be a crucial step in the pathogenesis of BD.
Additionally to an increased autoinflammatory response there is evidence of a dysregulated adaptive immune system, with a disturbed Th1/Th2 balance, expansion of Th17 cells and possibly a decrease in regulatory T cells, resulting in a surplus in pro-inflammatory cytokines.
The inflammation causes a typical clinical phenotype including orogenital ulcerations, uveitis and skin lesions. Treatment is aimed at the aberrations found in the innate (neutrophils and γδ-T cells) and adaptive immune system (TNF-α, INF-γ, IL-1), directed at organ involvement and individualized based on patient characteristics.
Conclusion
We presented an extensive review into the pathogenesis and treatment options of BD.
Objectives:
Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular manifestations in childhood and adult BD.
Methods:
Medline, Web of Science and Cochrane databases were searched from inception to October 5, 2018 to identify publications related to Behçet's disease comprising minimum twenty patients and providing the frequency of ocular manifestations (OC). Random effects models were used to combine the prevalence of OC in adults and children with BD. Heterogeneity was evaluated using I2.
Results:
The search resulted in 3129 articles, of which 51 were included in meta-analysis. OCs were slightly more frequent in childhood onset BD with the mean [95% Confidence Interval] frequency of 45 [34-56%] compared to 36 [29-43%] in adults, however, this difference was not statistically significant (p=0.198). In both children and adults, posterior uveitis (children 27% vs. adults 25%, and retinal vasculitis in adults 16%) was the most common ocular manifestation, followed by anterior uveitis (children 18% vs. adults 23%). When comparing the distribution of OC in Behcet's in adults, there was geographic variation where OC were higher in Turkey and the Middle East 42%, followed by Europe and North America (36%), North Africa 26% and East Asia 25% but not significantly (p=0.27).
Conclusions:
Ocular manifestations, predominantly uveitis; are common in BD. Ocular manifestations are not proportionately more frequent in adults with BD along the ancient Silk Road.
Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn’s disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life. Behçet syndrome is a recurrent multiorgan inflammatory disorder and a systemic vasculitis that predominantly affects veins. This Primer reviews the epidemiology, pathophysiology, diagnosis and treatment of Behçet syndrome and describes its effect on patient quality of life and the future outlook for the field.
Purpose:
To determine classification criteria for Behçet disease uveitis.
Design:
Machine learning of cases with Behçet disease and 5 other panuveitides.
Methods:
Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set.
Results:
One thousand twelve of cases panuveitides, including 194 cases of Behçet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behçet disease uveitis were a diagnosis of Behçet disease using the International Study Group for Behçet Disease criteria and a compatible uveitis, including: 1) anterior uveitis; 2) anterior chamber and vitreous inflammation; 3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or 4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behçet disease uveitis were 0.6 % in the training set and 0% in the validation set, respectively.
Conclusions:
The criteria for Behçet disease uveitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.
Purpose: This study aimed to evaluate biosimilar adalimumab’s efficacy and safety in patients with Behçet’s uveitis in Iran.
Methods: We performed a study on patients who mostly (79.2%) had a failure on conventional treatment with the mean follow-up time of 19.24 months (95% confidence interval (CI), 16.52–21.96). All the enrolled patients were anti-tumor necrosis factor (anti-TNF) naiive. The primary endpoint was best-corrected visual acuity (BCVA) improvement, and the secondary endpoints were changes in macular thickness, vitreous haze grade, anterior chamber (AC) cell grade, prednisolone dose, and the incidence of adverse reactions.
Results: Forty-eight patients were enrolled in the study. After adalimumab use, visual acuity improved significantly (p-value˂.001); vitreous haze grade decreased (p-value˂.001), and AC cell grade improved (p-value = .002). Macular thickness decreased, but its change was not statistically significant (p-value = .1). Moreover, adalimumab showed a corticosteroid-sparing effect (p-value = .03).
Conclusion: Biosimilar adalimumab (CinnoRA®) is effective and well-tolerated in Behçet’s uveitis.
Purpose:
Several concerns have arisen with biosimilars in terms of immunogenicity, safety issues, loss of efficacy, and extrapolation to other indications. The study aim was to evaluate the efficacy of SB5, an adalimumab biosimilar, in noninfectious uveitis (NIU).
Design:
Retrospective nonrandomized study.
Methods:
Data from patients with refractory NIU treated with SB5 (Imraldi, Biogen) were analyzed at baseline, 3 months after SB5 initiation and at the last follow-up in terms of uveitis relapses, occurrence of retinal vasculitis, resolution of uveitic macular edema (UME), best-corrected visual acuity, glucocorticoids (GCs)-sparing effect and drug survival.
Results:
Uveitis relapses decreased from 121 relapses/100 patients/year in the 12 months before SB5 initiation to 4 relapses/100 patients/year during the first 12 months of treatment (P = 0.0004). Uveitis was inactive in 46/47 eyes at the end of the study period. The number of eyes with active retinal vasculitis decreased during the study period (P < 0.0001). At baseline, 6 eyes presented UME, whereas no eye had UME at the last follow-up. Mean best-corrected visual acuity increased from 7.7 ± 3.41 at baseline to 8.9 ± 2.46 at the last follow-up (P = 0.0045). Mean GCs daily dosage decreased from 18.33 ± 10.33 mg at baseline to 5.75 ± 2.29 mg at the last follow-up (P = 0.018). The cumulative SB5 retention rate was 91.8% at both 12- and 20-month follow-up.
Conclusions:
SB5 biosimilar is effective in NIU by drastically reducing uveitis relapses and the occurrence of retinal vasculitis. Moreover, SB5 biosimilar improved visual acuity, allowed a significant GCs-sparing effect and showed an excellent drug retention rate.
Purpose:
To study the safety of extended monthly intravitreal infliximab injections in patients with active posterior uveitis in Behcet's disease (APUBD).
Methods:
This is a prospective, interventional, noncomparative, open-label, pilot study of 9 monthly intravitreal infliximab injections (1mg/0.05ml) for twenty-two eyes of 16 patients with APUBD. Control of inflammation and visual outcomes were assessed, and ocular complications were monitored during the study period.
Results:
Successful treatment was achieved in 7 eyes (35%) and failure was encountered in 13 eyes (65%). Only seven eyes of 6 patients (35%) had completed the study and achieved complete resolution of inflammation with improved BCVA, and no complications. Failure was either due to inability to control the inflammation in 9 eyes (45%) or development of exacerbation of inflammation in 4 eyes (20%). Four eyes developed severe immunological reaction from the drug following first (n=1), second (n=2), and third (n=1) injections and had to discontinue the injections. Kaplan-Meier survival analysis showed that the mean estimated time to failure was 3.3±0.2 months and all failed eyes required revision of their systemic immunotherapy to control the ocular inflammation.
Conclusion:
Intravitreal infliximab for APUBD was associated with a high complication rate and failure to control inflammation in the majority of eyes. It should not be considered a substitute to systemic therapy.
Introduction: Behçet’s disease uveitis (BDU) is a potentially blinding disorder. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) is mandatory in patients with intraocular inflammation involving the posterior segment of the eye.
Areas covered: This article discusses existing systemic treatment with corticosteroids and conventional and biologic DMARDs as well as adjunctive local therapy in BDU. An overview is provided for a wide range of biologic DMARDs that have shown promise or investigated in clinical trials. Most recently introduced biologic DMARDs and targeted synthetic DMARDs are also reviewed for their potential in the treatment of BDU.
Expert opinion: The prognosis of patients with BDU has remarkably improved after the introduction of biologic DMARDs. An expanding therapeutic armamentarium will allow treatment of most refractory cases. The ultimate goal is to provide drug-free remission with preservation of 20/20 vision.
Background:
To evaluate long-term efficacy of infliximab (IFX) in refractory uveoretinitis associated with Behçet's disease (BD) depending on uveoretinitis duration.
Methods:
Records of 16 patients with BD (32 eyes) followed for >5 years after starting IFX, were retrospectively reviewed. Long-term efficacy was compared between patients with short duration (≤18 months, n=7) versus long duration (>18 months, n=9) of their uveoretinitis prior to starting IFX.
Results:
The median follow-up after starting IFX was 132 months (76-146 months). Mean frequency of attacks and the 1-year Behçet's Disease Ocular Attack Score 24 decreased significantly over 10 years. Overall, the percentage of eyes with a best-corrected visual acuity (BCVA) ≥1.0 increased from 47% at baseline to 59% at 5 years; the percentage of eyes with a BCVA ≤0.1 was 19% at both baseline and 5 years. The frequency of ocular attacks decreased similarly in both short duration and long duration groups; however, the percentage of eyes with a BCVA ≥1.0 at 5 years was 100% in the short duration group versus 28% in the long duration group. IFX was discontinued in four patients with an excellent response to IFX therapy; all were young male patients in the short duration group with good BCVA bilaterally, and none had inflammatory recurrences over a median follow-up of 56 months off IFX.
Conclusion:
Initiation of IFX therapy in patients with BD within 18 months of their uveoretinitis onset was more effective in maintaining good BCVA than after 18 months.
Purpose
The efficacy of infliximab (IFX) and adalimumab (ADA) for treating Behçet’s syndrome (BS) and sarcoidosis has not been compared adequately.
Methods
We reviewed the medical records of patients with uveitis diagnosed at Tokyo Medical University Hospital and compared the efficacy of IFX and ADA for BS and the efficacy of ADA for sarcoidosis and BS.
Results
68 patients in IFX group and 63 patients in ADA group were analyzed. In BS patients, IFX and ADA were both effective in improving uveitic macular edema (UME). ADA improved UME in BS but not in sarcoidosis patients. The efficacy of ADA in reducing doses of corticosteroids and glaucoma medications was better in sarcoidosis than in the BS group.
Conclusion
Both IFX and ADA are efficacious in improving UME in BS patients. The reason that ADA improves UME better in BS than in sarcoidosis may be due to the difference in pathogenesis between these diseases.
Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.
Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.
Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.
Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.
Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.
In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases. In this Perspective article, the authors recount the earliest stages of translational research into IL-6 biology and the subsequent development of therapeutic IL-6 pathway inhibitors for the treatment of autoimmune rheumatic diseases and potentially numerous other indications.
Purpose
Evaluate the efficacy of weekly adalimumab (ADA) in patients with non-infectious ocular inflammation who failed standard every other week (EOW) dosing.
Design
Single-center, retrospective, study.
Subjects
Patients with uncontrolled inflammation on ADA EOW who were escalated to weekly dosing.
Methods
Chart review conducted at Northwestern University, January 2012 to April 2019.
Outcome: Number of treatment successes on weekly ADA at 6 and 12 months.
Results
Fourteen of 25 patients (56%) achieved disease control at 6 months; no additional failures occurred at 12 months.
Conclusion
Weekly ADA is a reasonable treatment option in patients with recalcitrant inflammation on standard dosing.
Purpose: To develop an algorithm for the diagnosis of Behçet’s disease (BD) uveitis based on ocular findings.
Methods: Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion.
Results: We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis.
Conclusion: This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.
Purpose: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon’s (PST) corticosteroid injections for noninfectious uveitis.
Methods: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.
Results: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, p = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, p = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.
Conclusion: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.