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Usefulness of Adalimumab in the Treatment of Refractory Uveitis Associated with Juvenile Idiopathic Arthritis  [PDF]
Carmen García-De-Vicu?a,Manuel Díaz-Llopis,David Salom,Rosa Bou,Jesus Díaz-Cascajosa,Miguel Cordero-Coma,Gabriela Ortega,Norberto Ortego-Centeno,Marta Suarez-De-Figueroa,Juan Cruz-Martínez,Alex Fonollosa,Ricardo Blanco,ángel María García-Aparicio,Jose M. Benítez-Del-Castillo,Jordi Antón
Mediators of Inflammation , 2013, DOI: 10.1155/2013/560632
Abstract: Purpose. To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. Design. Multicenter, prospective case series. Methods. Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13–17 years were treated with 40?mg of adalimumab every other week for 6 months and those aged 4–12 years received 24 mg/m2 body surface. Results. Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit ( ). The mean (SD) macular thickness at baseline was 304.54 (125.03)?μ and at the end of follow-up was 230.87 (31.12)?μ ( ). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit ( ). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02)?mg ( ). No significant side effects requiring discontinuation of therapy were observed. Conclusion. Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement. 1. Introduction Uveitis is a well-known extra-articular manifestation of spondyloarthritides, which may lead to severe functional impairment [1]. Childhood uveitis is relatively rare and may be secondary to a variety of causes. The majority of children with uveitis have idiopathic uveitis, with uveitis secondary to juvenile idiopathic arthritis (JIA) being the second most common diagnosis [2, 3]. Uveitis occurs in around 10–15% of the patients with JIA, although most reports are retrospective and describe referral centers’ experiences rather than population-based studies [4]. It has been largely recognized that uveitis is a serious manifestation of JIA. Complications increase with the duration of the disease, with a potential for cataract, glaucoma, band keratopathy, synechiae, macular edema, and significant ocular damage with impaired vision and even blindness [5, 6]. Antinuclear antibody (ANA)—positive girls younger than 7 years of age with oligoarticular JIA are at the greatest risk of developing eye disease [7]. Presence of complications at first visit and uveitis manifestation before arthritis have been identified as predictors for complications [8, 9]. JIA-associated refractory chronic uveitis is a challenge for treatment. Topical and systemic corticosteroids are the first-line standard therapy,
Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis
Kotaniemi K, S il H, Kautiainen H
Clinical Ophthalmology , 2011, DOI: http://dx.doi.org/10.2147/OPTH.S23646
Abstract: ng-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis Original Research (3269) Total Article Views Authors: Kotaniemi K, S il H, Kautiainen H Published Date October 2011 Volume 2011:5 Pages 1425 - 1429 DOI: http://dx.doi.org/10.2147/OPTH.S23646 Kaisu Kotaniemi1,2, Hanna S il 2, Hannu Kautiainen3 1Helsinki University Hospital, Helsinki, Finland; 2Orton Orthopaedic Hospital and Rehabilitation Unit, Helsinki, Finland; 3Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland Background: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis. Methods: Adalimumab was initiated in 94 patients with juvenile idiopathic arthritis to treat active arthritis and/or active associated uveitis. In 18 patients, therapy was discontinued after a short period because of inefficacy or side effects. The activity of uveitis (using Standardized Uveitis Nomenclature [SUN] criteria and clinical examination) and arthritis (number of swollen or active joints) was evaluated at the start and at end of the study. Results: At the end of the study, uveitis was under good clinical control in two thirds of 54 patients (31% did not need any local treatment and 35% used only 1–2 corticosteroid drops a day), and one third had active uveitis (at least three corticosteroid drops a day). According to SUN criteria, adalimumab treatment for uveitis showed improved activity (a two-fold decrease in uveitis activity) in 28% of patients, with a moderate response in 16 patients, no change in a further 16 patients, and worsening activity (a two-fold increase in uveitis activity) in 13% of patients. The overall proportion of patients with active arthritis decreased. At the beginning of the study, 69% of patients with uveitis had more than two active joints, and at the end of the study only 27% had active joint disease. In 27 patients with juvenile idiopathic arthritis without uveitis on adalimumab, the number of active joints decreased from 93% to 59%. Systemic corticosteroid treatment could be stopped in 22% of patients with uveitis and in 11% of those without uveitis. Most of the patients had received methotrexate, other immunosuppressive therapy, or other biological drugs before initiating adalimumab. Conclusion: Adalimumab is a valuable option in the treatment of uveitis associated with active juvenile idiopathic arthritis.
Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis  [cached]
Kotaniemi K,Säilä H,Kautiainen H
Clinical Ophthalmology , 2011,
Abstract: Kaisu Kotaniemi1,2, Hanna S il 2, Hannu Kautiainen31Helsinki University Hospital, Helsinki, Finland; 2Orton Orthopaedic Hospital and Rehabilitation Unit, Helsinki, Finland; 3Unit of Primary Health Care, Kuopio University Hospital, Kuopio, FinlandBackground: The purpose of this study was to investigate the long-term effects of adalimumab, a tumor necrosis factor alpha antagonist, in the treatment of uveitis associated with juvenile idiopathic arthritis.Methods: Adalimumab was initiated in 94 patients with juvenile idiopathic arthritis to treat active arthritis and/or active associated uveitis. In 18 patients, therapy was discontinued after a short period because of inefficacy or side effects. The activity of uveitis (using Standardized Uveitis Nomenclature [SUN] criteria and clinical examination) and arthritis (number of swollen or active joints) was evaluated at the start and at end of the study.Results: At the end of the study, uveitis was under good clinical control in two thirds of 54 patients (31% did not need any local treatment and 35% used only 1–2 corticosteroid drops a day), and one third had active uveitis (at least three corticosteroid drops a day). According to SUN criteria, adalimumab treatment for uveitis showed improved activity (a two-fold decrease in uveitis activity) in 28% of patients, with a moderate response in 16 patients, no change in a further 16 patients, and worsening activity (a two-fold increase in uveitis activity) in 13% of patients. The overall proportion of patients with active arthritis decreased. At the beginning of the study, 69% of patients with uveitis had more than two active joints, and at the end of the study only 27% had active joint disease. In 27 patients with juvenile idiopathic arthritis without uveitis on adalimumab, the number of active joints decreased from 93% to 59%. Systemic corticosteroid treatment could be stopped in 22% of patients with uveitis and in 11% of those without uveitis. Most of the patients had received methotrexate, other immunosuppressive therapy, or other biological drugs before initiating adalimumab.Conclusion: Adalimumab is a valuable option in the treatment of uveitis associated with active juvenile idiopathic arthritis.Keywords: adalimumab, juvenile idiopathic arthritis, uveitis
Long-term use of adalimumab in the treatment of rheumatic diseases
Charalampos Papagoras, Paraskevi V Voulgari, Alexandros A Drosos
Open Access Rheumatology: Research and Reviews , 2009, DOI: http://dx.doi.org/10.2147/OARRR.S4297
Abstract: ng-term use of adalimumab in the treatment of rheumatic diseases Review (5817) Total Article Views Authors: Charalampos Papagoras, Paraskevi V Voulgari, Alexandros A Drosos Published Date May 2009 Volume 2009:1 Pages 51 - 68 DOI: http://dx.doi.org/10.2147/OARRR.S4297 Charalampos Papagoras, Paraskevi V Voulgari, Alexandros A Drosos Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece Abstract: Adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-alpha (TNFα), has been evaluated in various randomized placebo-controlled trials in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In the short time frame of these trials adalimumab has been shown to be effective in reducing disease activity, slowing radiographic disease progression and improving patients’ quality of life, while at the same time demonstrating an acceptable safety profile. Furthermore, release of adalimumab on the market, prospective observational studies, as well as open-label extensions of the original double-blind trials have provided experience and data about the long-term efficacy and safety of the drug. Initial effectiveness, in terms of reducing disease activity, is sustained, while in most cases patients treated with adalimumab experienced a slower radiographic progression and consequently less disability and improved health-related quality-of-life outcomes. Moreover, long-standing treatment of thousands of patients with adalimumab outside the controlled context of clinical trials was not related to new safety signals, with the most common adverse events being respiratory infections. The most common serious adverse events seem to be tuberculosis reactivation, while a putative association with malignant lymphoma development is not yet proven. Besides, both of these adverse reactions pertain to the whole TNFα blocker group. In conclusion, adalimumab is a safe and effective option for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis.
Psoriatic Juvenile Idiopathic Arthritis Associated with Uveitis: A Case Report  [PDF]
Davide Moretti,Ilaria Cianchi,Gaia Vannucci,Rolando Cimaz,Gabriele Simonini
Case Reports in Rheumatology , 2013, DOI: 10.1155/2013/595890
Abstract: According to the definition proposed by the International League of Associations for Rheumatology (ILAR), juvenile idiopathic arthritis (JIA) is defined as an arthritis of unknown etiology, starting under 16 years of age and lasting for at least 6 weeks, once other known conditions have been excluded. JIA represents the most common chronic rheumatic disease of childhood and is considered an important cause of short- and long-term acquired disability in children. It is currently estimated that psoriatic JIA represents up to 10% of all JIA subtypes, and chronic uveitis may occur in 10 to 15% of children with psoriatic JIA. In this report we describe a case of psoriatic JIA complicated by uveitis, in a child failing previous treatments with nonsteroidal anti-inflammatory drugs, methotrexate, and etanercept. Finally, adalimumab was prescribed, which led to sustained clinical remission in both arthritis and uveitis. 1. Background According to the definition proposed by the International League of Associations for Rheumatology (ILAR), juvenile idiopathic arthritis (JIA) is defined as an arthritis of unknown etiology, starting before 16 years of age, and lasting for at least 6 weeks, once other known conditions have been excluded [1]. JIA represents the most common chronic rheumatic disease of childhood and is considered an important cause of short- and long-term acquired disability in children [2]. JIA encompasses seven different subcategories based on the predominant clinical manifestations and laboratory features seen in the first 6 months of disease. Its prevalence is unknown and varies considerably among populations, depending on race, immunogenetic susceptibility, and environmental influences. Currently, the annual incidence of JIA is estimated at around 100 new cases per 1,000,000 population [3]. JIA is considered an autoimmune disease, potentially resulting from an abnormal immunologic response caused or triggered by environmental factors such as infection or trauma in a genetically predisposed subject. Adaptive immune activation against self-epitopes has been suggested, and a typical synovial membrane inflammation has been observed [4–6]. The synovia shows pronounced hyperplasia of the lining layer, along with an exuberant infiltration of the sublining layer with mononuclear cells, including memory T cells, B cells, macrophages, dendritic cells, and plasma cells [2]. Psoriatic JIA represents up to 10% of all JIA subtypes and has a predilection for females. Anti-nuclear antibodies (ANAs) are positive in more than 50% of affected patients. According to
Recent developments in anti-rheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis
Kristen Hayward, Carol A Wallace
Arthritis Research & Therapy , 2009, DOI: 10.1186/ar2619
Abstract: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune-autoinflammatory disease of unknown etiology. It is estimated that JIA affects up to 1 in 1,000 children worldwide and is the most common cause of autoimmune musculoskeletal disease in children [1]. By definition, children with JIA have disease onset prior to age 16 years, and present with joint pain, stiffness and swelling that persists for longer than 6 weeks. Formerly referred to as juvenile rheumatoid arthritis, the classification scheme for JIA was updated by the International League of Associations for Rheumatology in 2001 to reflect the unique nature of arthritis in childhood and to distinguish JIA from adult-onset rheumatoid arthritis (RA) [2]. Based on these criteria, JIA is subdivided into categories based on the number of joints affected and the presence or absence of specific serologic findings and systemic manifestations (Table 1).Without appropriate treatment, JIA may result in devastating consequences. Children may experience permanent disability from joint destruction, growth deformities or blindness (from chronic uveitis associated with JIA) [3,4]. In the case of the systemic-onset form of JIA (SOJIA), untreated disease may even result in multiple organ failure and death.Twenty years ago it was commonly believed that childhood-onset arthritis might subside in adulthood. Recent studies, however, have demonstrated that sustained resolution of disease occurs in only a small minority of JIA patients (as many as 50% of children with JIA enter adulthood with ongoing, active disease) [3]. Additional information from a recent large, multicenter, retrospective study indicates that patients diagnosed with JIA experience a chronic course involving cycling of disease between active and inactive states over the course of years. Although 196 out of 437 JIA patients followed over a median of 7 years achieved a period of 1 year without any JIA symptoms off all medications, less than 20% of patients had two
Tocilizumab in the treatment of systemic juvenile idiopathic arthritis
Murakami M,Tomiita M,Nishimoto N
Open Access Rheumatology: Research and Reviews , 2012,
Abstract: Miho Murakami,1 Minako Tomiita,2,3 Norihiro Nishimoto11Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, 2Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, 3Department of Allergy and Rheumatology, Chiba Children's Hospital, Chiba, JapanAbstract: Systemic juvenile idiopathic arthritis is one of the common rheumatic diseases in childhood and characterized by spiking fever, evanescent skin rash, lymphadenopathy, hepatosplenomegaly, and serositis, in addition to arthritis. Children with systemic juvenile idiopathic arthritis often show growth retardation and developmental abnormality, as well as macrophage activation syndrome, a life-threatening complication. Overproduction of interleukin-6 is pathologically responsible for the systemic inflammatory manifestations and abnormal laboratory results with systemic juvenile idiopathic arthritis. Thus, tocilizumab, a humanized antihuman interleukin-6 receptor antibody, has been developed as a therapeutic agent for the disease. A series of clinical studies have demonstrated the excellent efficacy and safety of tocilizumab for patients with active disease. Tocilizumab was approved for systemic juvenile idiopathic arthritis in Japan in 2008 and in the European Union and the United States in 2011.Keywords: systemic juvenile idiopathic arthritis, tocilizumab, antihuman interleukin-6 receptor antibody, biologics
New Advances in Juvenile Idiopathic Arthritis  [PDF]
Jing-Long Huang
Chang Gung Medical Journal , 2012,
Abstract: Juvenile idiopathic arthritis (JIA) comprises a group ofheterogeneous disorders of chronic arthritis in childhood withno apparent etiology. Juvenile idiopathic arthritis is the mostcommon pediatric rheumatic disease and is associated withsignificant long-term morbidity and mortality. There have beenmajor advances in recent years in our understanding of thepathogenesis of JIA, the definition of disease control, and biological treatments for JIA. Multiple environmental and geneticfactors have been linked with the onset and / or the exacerbation of JIA, including perinatal factors, viral and bacterialinfections, epigenetic factors, and malnutrition. However, nosingle causative factor has been identified to date. As ourunderstanding of the complex network of immune cells andinflammatory cytokines has improved, biologics have beendeveloped to modulate the inflammatory processes. Indeed, anumber of such biologics have been demonstrated effective for the treatment of JIA.Although biologic agents may alleviate the inflammation associated with JIA and preventdisability caused by joint destruction, continued and comprehensive observation is requiredto determine the long-term outcomes associated with such treatment
The role of adalimumab in rheumatic and autoimmune disorders: comparison with other biologic agents
Reimold AM
Open Access Rheumatology: Research and Reviews , 2012, DOI: http://dx.doi.org/10.2147/OARRR.S14569
Abstract: ole of adalimumab in rheumatic and autoimmune disorders: comparison with other biologic agents Review (2061) Total Article Views Authors: Reimold AM Published Date May 2012 Volume 2012:4 Pages 33 - 47 DOI: http://dx.doi.org/10.2147/OARRR.S14569 Received: 18 January 2012 Accepted: 29 February 2012 Published: 08 May 2012 Andreas M Reimold Dallas Veterans Affairs Medical Center and Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, TX, USA Abstract: Adalimumab (ADA) is a biologic medication that dampens inflammatory pathways by binding to the cytokine tumor necrosis factor alpha. The US Food and Drug Administration has approved ADA as a medication for use in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, and juvenile idiopathic arthritis. This year marks 10 years of clinical experience with ADA. Long-term extension studies of some of the initial clinical trials, as well as data from large patient registries, are demonstrating ongoing benefit for responders. Potential side effects such as increased risk of infection, lymphoma, congestive heart failure, and demyelination continue to be examined, as the available data are not unanimous in showing an increase in incidence. In balancing both the advantages and the disadvantages of using ADA, the drug's overall effectiveness and its availability for use in patients with hepatic or renal comorbidities are weighed against the high cost. ADA is expected to have a leading role in the treatment of rheumatoid arthritis and other inflammatory conditions for years to come. Future studies will need to address the optimal sequence of disease-modifying antirheumatic drugs and biologics to use, combinations of disease-modifying antirheumatic drugs and biologics, and head-to-head comparisons of biologics in clinical trials. For those who go into clinical remission on an anti-tumor necrosis factor medication, unanswered questions remain about identifying the patients who can maintain the remission off all drugs, or at least off injected medication. Given the cost of biologic drugs, even studies that increase the interval between drug doses in well-controlled patients could provide financial benefits.
The role of adalimumab in rheumatic and autoimmune disorders: comparison with other biologic agents
Reimold AM
Open Access Rheumatology: Research and Reviews , 2012,
Abstract: Andreas M ReimoldDallas Veterans Affairs Medical Center and Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas, TX, USAAbstract: Adalimumab (ADA) is a biologic medication that dampens inflammatory pathways by binding to the cytokine tumor necrosis factor alpha. The US Food and Drug Administration has approved ADA as a medication for use in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, and juvenile idiopathic arthritis. This year marks 10 years of clinical experience with ADA. Long-term extension studies of some of the initial clinical trials, as well as data from large patient registries, are demonstrating ongoing benefit for responders. Potential side effects such as increased risk of infection, lymphoma, congestive heart failure, and demyelination continue to be examined, as the available data are not unanimous in showing an increase in incidence. In balancing both the advantages and the disadvantages of using ADA, the drug's overall effectiveness and its availability for use in patients with hepatic or renal comorbidities are weighed against the high cost. ADA is expected to have a leading role in the treatment of rheumatoid arthritis and other inflammatory conditions for years to come. Future studies will need to address the optimal sequence of disease-modifying antirheumatic drugs and biologics to use, combinations of disease-modifying antirheumatic drugs and biologics, and head-to-head comparisons of biologics in clinical trials. For those who go into clinical remission on an anti-tumor necrosis factor medication, unanswered questions remain about identifying the patients who can maintain the remission off all drugs, or at least off injected medication. Given the cost of biologic drugs, even studies that increase the interval between drug doses in well-controlled patients could provide financial benefits.Keywords: rheumatoid arthritis, Humira , tumor necrosis factor alpha, disease-modifying antirheumatic drug
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