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Changes in the number of patients with vasculitis, retinitis, and papillitis throughout the study period.
Source publication
Purpose:
To assess the safety and efficacy of intravitreal infliximab (1 mg/0.05 mL) in patients with refractory posterior uveitis in Behcet's disease.
Methods:
Twenty patients were included in this study. Best corrected visual acuity (BCVA), vitreous haze (graded 0-4), vasculitis, retinitis, and papillopathy (presence or absence) were assessed...
Contexts in source publication
Context 1
... was a statistically significant reduction in the number of patients with active vasculitis from 15 patients before injection to only 1 patient at the end of follow-up (P , 0.001). Before injections, there were 15 patients with active vasculitis, which continued to be reduced throughout the study period to 11 patients at Week 2, and dra- matic reduction to two patients at Week 4; then only one patient had vasculitis at Week 12 till the end of the study (Table 2, Figure 3). Preinjections, there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). ...
Context 2
... injections, there were 15 patients with active vasculitis, which continued to be reduced throughout the study period to 11 patients at Week 2, and dra- matic reduction to two patients at Week 4; then only one patient had vasculitis at Week 12 till the end of the study (Table 2, Figure 3). Preinjections, there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). Preinjection, there were two patients with papillopathy, 1 patient at Week 2, and none at Week 4 (P , 0.001) till the end of follow-up (Table 2, Figure 3). ...
Context 3
... there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). Preinjection, there were two patients with papillopathy, 1 patient at Week 2, and none at Week 4 (P , 0.001) till the end of follow-up (Table 2, Figure 3). ...
Context 4
... was a statistically significant reduction in the number of patients with active vasculitis from 15 patients before injection to only 1 patient at the end of follow-up (P , 0.001). Before injections, there were 15 patients with active vasculitis, which continued to be reduced throughout the study period to 11 patients at Week 2, and dra- matic reduction to two patients at Week 4; then only one patient had vasculitis at Week 12 till the end of the study (Table 2, Figure 3). Preinjections, there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). ...
Context 5
... injections, there were 15 patients with active vasculitis, which continued to be reduced throughout the study period to 11 patients at Week 2, and dra- matic reduction to two patients at Week 4; then only one patient had vasculitis at Week 12 till the end of the study (Table 2, Figure 3). Preinjections, there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). Preinjection, there were two patients with papillopathy, 1 patient at Week 2, and none at Week 4 (P , 0.001) till the end of follow-up (Table 2, Figure 3). ...
Context 6
... there were nine patients with active retinitis that was sig- nificantly (P , 0.001) reduced to three patients at Week 2, then none at Week 4 and for the rest the study period (Table 1, Figure 3). Preinjection, there were two patients with papillopathy, 1 patient at Week 2, and none at Week 4 (P , 0.001) till the end of follow-up (Table 2, Figure 3). ...
Citations
... Hamza et al. demonstrated the safety and efficacy of a single 1 mg/0.05 ml intravitreal IFX injection in 20 patients with refractory uveitis due to BD [37]. At 18 weeks of follow-up, they observed statistically significant improvements in mean visual acuity, reductions in mean central macular thickness, and decreased mean vitreous haze scores. ...
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.
... A first study of 15 patients with BD uveitis treated with intravitreal infliximab injections (1.5 mg intravitreal infliximab) showed a significant improvement in best-corrected visual acuity, with a significant reduction in macular thickness, retinal vasculitis, and retinitis [76]. Similarly, another study showed that intravitreal infliximab appeared to be safe and effective in the treatment of uveitis in 20 BD's patients [77]. However, conflicting results regarding its safety and efficacy have been published in a study of 16 patients. ...
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.
... Hence, this possibility has been raised for the treatment of inflammatory ocular diseases. Some studies that have evaluated the effect of the intravitreal administration of IFX (dose between 1 and 1.5 mg) in patients with Behçet's syndrome uveitis have observed an improvement in central macular thickness and visual acuity, without appreciating adverse events [116,117]. The reported improvement in clinical parameters places intravitreal IFX as a promising strategy in the treatment of ocular inflammation. ...
Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians’ treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.
... No significant electrophysiological or ocular AEs were noted. 166 Another study by Markomichelakis et al. using a single intravitreal dose (1 mg/0.05 mL) showed significant improvement in BCVA, anterior chamber cells, vitreous haze, and CRT. ...
Systemic immunosuppressants and biologicals have been a valuable tool in the treatment of inflammatory diseases and malignancies. The safety profile of these drugs has been debatable, especially in localized systems, such as the eye. This has led to the search for fairly local approaches, such as intravitreal, subconjunctival, and topical route of administration. Immunosuppressants have been used as a second-line drug in patients intolerable to corticosteroids or those who develop multiple recurrences on weaning corticosteroids. Similarly, biologicals have also been used as the next line of therapy, when adequate control of inflammation could not be attained or immunosuppressants were contraindicated to patients. Intravitreal immunosuppressants, such as methotrexate and sirolimus, have been extensively studied in noninfectious posterior uveitis, whereas limited studies have established the efficacy of intravitreal biologicals, such as infliximab and adalimumab. Most of these drugs have shown good safety profile and tolerability in animal studies alone and have not been studied further in human subjects. However, most of the studies in literature are single-case reports or case series which limits the level of evidence. In this comprehensive review, we discuss the mechanism of action, pharmacodynamics, pharmacokinetics, indications, efficacy, and side effects of different intravitreal immunosuppressants and biologicals that have been studied in literature.
... Efficacy and safety of intravitreal infliximab was studied in animal models and human studies. [156][157][158][159] Human studies reported variable efficacy of intravitreal infliximab in controlling inflammation but raised safety concerns, including development of intraocular inflammatory response, [156] decreased electroretinogram amplitudes, and visual field measurements. [157] Intravitreal adalimumab has shown effectiveness in controlling inflammation and macular edema in small retrospective studies. ...
... Efficacy and safety of intravitreal infliximab was studied in animal models and human studies. [156][157][158][159] Human studies reported variable efficacy of intravitreal infliximab in controlling inflammation but raised safety concerns, including development of intraocular inflammatory response, [156] decreased electroretinogram amplitudes, and visual field measurements. [157] Intravitreal adalimumab has shown effectiveness in controlling inflammation and macular edema in small retrospective studies. ...
Uveitis is one of the most common causes of vision loss and blindness worldwide. Local and/or systemic immunosuppression is often required to treat ocular inflammation in noninfectious uveitis. An understanding of safety and efficacy of these medications is required to individualize treatment to each patient to ensure compliance and achieve the best outcome. In this article, we reviewed the effectiveness of systemic biologic response modifiers and local treatments commonly used in the management of patients with noninfectious uveitis.
... showed control of ocular inflammation and an acceptable safety profile in 20 patients with refractory Behcet uveitis across 18 weeks of follow-up. [21] There is a report of worsening of uveitis, with reduction in electroretinographic parameters, and deterioration in microperimetry, after treatment with intravitreal infliximab in a prospective open label study. [22] Adalimumab Adalimumab (Humira, AbbVie Inc., North Chicago, IL) is a human monoclonal antibody that blocks soluble and transmembrane TNF-α. ...
The management of noninfectious uveitis is constantly evolving. A new "biologic era" in treatment began after the effectiveness of tumor necrosis factor-alpha blocking drugs was demonstrated in rheumatologic inflammatory diseases. The goal of specific immunomodulation with a biologic drug is to target inflammation at the molecular level with a low rate of serious adverse events. The purpose of this review is to summarize current knowledge of biologic drugs in the treatment of noninfectious uveitis by describing clinical studies and recent pharmacological developments.
... 255 The efficacy of IVT-IFX in uveitis has been documented in causing improvement in vision, anatomical outcomes, and reduction in inflammation with no reported systemic side effects. [256][257][258] Twenty patients with refractory posterior uveitis in BD were given 3 IFX injections in a row (1 mg/ 0.05 mL) and found to be safe and effective. 258 However, these effects were short term, and reinjections were needed at intervals shorter than 6 weeks to achieve the best therapeutic goals. ...
... [256][257][258] Twenty patients with refractory posterior uveitis in BD were given 3 IFX injections in a row (1 mg/ 0.05 mL) and found to be safe and effective. 258 However, these effects were short term, and reinjections were needed at intervals shorter than 6 weeks to achieve the best therapeutic goals. Similarly, IVT management with ADA in uveitis has shown favorable results in few studies. ...
The arena of uveitis deals with a number of entities, which can be infectious or immune mediated. Noninfectious uveitis (NIU) has been managed with corticosteroids and immunosuppressives. However, their prolonged use has side effects limiting clinical utility in the long run. Improved knowledge regarding pathogenesis of uveitis and associated systemic disease has led to a new epoch in the development of treatment strategies, of which biologics are the recent ones. Biologics revolutionized the management of NIU especially uveitis associated with spondyloarthropathy and refractory uveitis. They target inflammation at a molecular level with less side effects. The most widely used are tumor necrosis factor-alpha inhibitors (infliximab and adalimumab). Other drugs include anti-CD20 inhibitors (rituximab), interleukin-6R-inhibitor (tocilizumab), Interleukin-1R-inhibitor (anakinra), Iinterleukin-2-inhibitor (daclizumab), and the list is further increasing. New advances in biologics are the biosimilar molecules, which are biological products that are highly similar to the reference product, and they include Infimab (biosimilar of infliximab), Exemptia or Adfrar (biosimilar of adalimumab), and Intacept or Etacept (biosimilar of etanercept). Other group of biologics are Janus Associated Kinase inhibitors (JAK-inhibitors), which are long-term oral treatment options of rheumatoid arthritis. They inhibit JAKs, which cause activation of signal transducer and activator of transcription (STAT) proteins, and initiate transcription of inflammatory genes. Many inflammatory cytokines that are implicated in pathogenesis of ocular inflammation are known to utilize the JAK/STAT-signaling pathway, including interleukin-2 (IL-2) and IL-6. Thus, biologics are the future of uveitis treatment with promising results. This article aims to summarize the current knowledge on biologics and their clinical utility in the management of NIU.
... 255 The efficacy of IVT-IFX in uveitis has been documented in causing improvement in vision, anatomical outcomes, and reduction in inflammation with no reported systemic side effects. [256][257][258] Twenty patients with refractory posterior uveitis in BD were given 3 IFX injections in a row (1 mg/ 0.05 mL) and found to be safe and effective. 258 However, these effects were short term, and reinjections were needed at intervals shorter than 6 weeks to achieve the best therapeutic goals. ...
... [256][257][258] Twenty patients with refractory posterior uveitis in BD were given 3 IFX injections in a row (1 mg/ 0.05 mL) and found to be safe and effective. 258 However, these effects were short term, and reinjections were needed at intervals shorter than 6 weeks to achieve the best therapeutic goals. Similarly, IVT management with ADA in uveitis has shown favorable results in few studies. ...
The arena of uveitis deals with a number of entities, which can be infectious or immune mediated. Noninfectious uveitis (NIU) has been managed with corticosteroids and immunosuppressives. However, their prolonged use has side effects limiting clinical utility in the long run. Improved knowledge regarding pathogenesis of uveitis and associated systemic disease has led to a new epoch in the development of treatment strategies, of which biologics are the recent ones. Biologics revolutionized the management of NIU especially uveitis associated with spondyloarthropathy and refractory uveitis. They target inflammation at a molecular level with less side effects. The most widely used are tumor necrosis factor-alpha inhibitors (infliximab and adalimumab). Other drugs include anti-CD20 inhibitors (rituximab), interleukin-6R-inhibitor (tocilizumab), Interleukin-1R-inhibitor (anakinra), Iinterleukin-2-inhibitor (daclizumab), and the list is further increasing. New advances in biologics are the biosimilar molecules, which are biological products that are highly similar to the reference product, and they include Infimab (biosimilar of infliximab), Exemptia or Adfrar (biosimilar of adalimumab), and Intacept or Etacept (biosimilar of etanercept). Other group of biologics are Janus Associated Kinase inhibitors (JAK-inhibitors), which are long-term oral treatment options of rheumatoid arthritis. They inhibit JAKs, which cause activation of signal transducer and activator of transcription (STAT) proteins, and initiate transcription of inflammatory genes. Many inflammatory cytokines that are implicated in pathogenesis of ocular inflammation are known to utilize the JAK/STAT-signaling pathway, including interleukin-2 (IL-2) and IL-6. Thus, biologics are the future of uveitis treatment with promising results. This article aims to summarize the current knowledge on biologics and their clinical utility in the management of NIU.
... A first study of 15 patients with BD uveitis treated with intravitreal infliximab injections (1.5 mg intravitreal infliximab) showed a significant improvement in visual acuity, with a significant decrease in retinal vasculitis, retinitis and macular thickness [114]. Similarly, a second study showed that intravitreal infliximab appeared to be safe and effective in treating uveitis in 20 BD patients [115]. However, contradictory results regarding its safety and efficacy have also been reported in a more recent study in 16 patients. ...
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.
... İnterferonlar immünomodülatuar etkisi nedeniyle dirençli Behçet olgularında endikasyon dışı başvuru gereksinimi olmaksızın kullanılmaktadır (6). İnfliksimab, TNF-α molekülüne bağlanarak bu molekülün TNF-α reseptörlerine bağlanmasını engellemekte ve arka üveit, retinal vaskülit ile maküla ödemi olan dirençli Behçet olgularında kalıcı remisyon sağlamak için endikasyon dışı ilaç kullanımı tercih edilebilmektedir (5,7,8). Diğer bir Anti-TNF ajanı olan adalimumab noninfeksiyöz orta, posterior ve panüveitlerde, randomize çift kör faz III çalışmalarında etkinlik gösterdiği kanıtlanmış bir biyolojik ajandır. ...
INTRODUCTION: To assess demographic characteristics in patients with ocular Behçet's disease who use off-label drugs in Turkey. METHODS: The applications for off-label drug use (infliximab, adalimumab, mycophenolat mofetil) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were evaluated retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens and reasons for referral. RESULTS: The study included 124 patients who were admitted for off-label drug use. The mean age of the patients was 32.1 +- 7.9 years. While 72.6% of all applications were male, 27.4% were female. Seventy-eight percent of the applicants were from Marmara and Central Anatolia. Infliximab was the most applied off-label drug in ocular Behçet's disease at a rate of 75% in Turkey. When the hospitals that applied were taken, the state universities took the first place with a ratio of 88% and the education and research hospitals came to the fore with a 6.5% rate. DISCUSSION AND CONCLUSION: Examination of demographic data on off-label drug use can be a guide in terms of providing the necessary convenience in legislation in line with drug preferences.
