Anti–Interleukin‐6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis–Associated Uveitis Refractory to Anti–Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty‐Five Patients

Calvo-Río, V.; Santos-Gόmez, M.; Calvo, Inmaculada; González-Fernández, María; López-Montesinos, Berta; Mesquida, Marina; Adán, Alfredo; Hernández, M.V.; Maíz, O.; Atanes, A.; Bravo, Beatriz Navarro; Modesto, Consuelo; Díaz-Cordovés, Gisela; Palmou-Fontana, Natalia; Loricera, J.; González‐Vela, M. Carmen; Demetrio‐Pablo, Rosalía; Hernández, José L.; Blanco, Ricardo

doi:10.1002/art.39940

Cited by 144 publications

(77 citation statements)

References 43 publications

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“…Based on the current literature, recommended alternative nonbiologic options are mycophenolate mofetil (40), leflunomide (41), or cyclosporine (42), and recommended alternative biologic options are abatacept (43)(44)(45) or tocilizumab (46,47); however, evidence supporting preference for a specific nonbiologic or biologic DMARD, combination therapies, and timing of initiation beyond methotrexate, adalimumab, and infliximab is currently lacking. Based on the current literature, recommended alternative nonbiologic options are mycophenolate mofetil (40), leflunomide (41), or cyclosporine (42), and recommended alternative biologic options are abatacept (43)(44)(45) or tocilizumab (46,47); however, evidence supporting preference for a specific nonbiologic or biologic DMARD, combination therapies, and timing of initiation beyond methotrexate, adalimumab, and infliximab is currently lacking.…”

Section: Recommendation 15mentioning

confidence: 99%

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

Angeles‐Han

Ringold

Beukelman

et al. 2019

Arthritis Care & Research

206

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Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the health care provider in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions. These recommendations cannot adequately convey all uncertainties and nuances of patient care.The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service.Objective. To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).Methods. Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong.Results. Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because ANGELES-HANETAL 704 | of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss.Conclusion. This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE...

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Section: Recommendation 15mentioning

confidence: 99%

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

Angeles‐Han

Ringold

Beukelman

et al. 2019

Arthritis Care & Research

206

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“…This has led to the clinical trials of tocilizumab, with several studies showing its efficacy in improving visual acuity and CME in cases of recalcitrant uveitis, with minimal adverse events associated with therapy . Multiple retrospective case series show similar results of efficacy and safety . A recent multicentre retrospective study on patients with JIA‐associated uveitis (refractory to ≥1 TNF‐α inhibitor) treated with tocilizumab showed that 88.2% of patients had complete control of ocular inflammation at 12 months .…”

Section: Il Blockersmentioning

confidence: 99%

“…[85][86][87][88][89][90][91] Multiple retrospective case series show similar results of efficacy and safety. [92][93][94][95] A recent multicentre retrospective study on patients with JIA-associated uveitis (refractory to ≥1 TNF-α inhibitor) treated with tocilizumab showed that 88.2% of patients had complete control of ocular inflammation at 12 months. 93 There was a significant reduction in concomitant corticosteroid dosage and a statistically significant improvement in CMT and visual acuity.…”

Section: Il Blockers Tocilizumabmentioning

confidence: 99%

The use of biologic agents in the management of uveitis

Trivedi

Katelaris

2019

Internal Medicine Journal

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The uveitides are a heterogenous group of ocular inflammatory disorders that account for the third highest cause of blindness worldwide, responsible for 5–10% of visual impairment globally. Up to 35% of patients with uveitis can suffer significant vision loss. To prevent irreversible structural damage and blindness, it is important that the diagnosis and commencement of appropriate therapy occurs promptly. Management includes topical and systemic corticosteroid therapy and conventional immunomodulatory agents, including methotrexate, azathioprine, mycophenolate mofetil and cyclosporin. Significant progress has been made in the past decade in our understanding of the immunopathological pathways that drive intraocular inflammation, allowing the development of targeted therapy with biologic agents. These include TNF‐α inhibitors, such as infliximab, adalimumab and etanercept; interleukin blockers, such as tocilizumab and daclizumab; and other targeted therapies, such as rituximab and abatacept. The efficacy of these agents has been studied in cases of severe uveitis that are refractory to conventional immunomodulatory agents and provide exciting results that have revolutionised uveitis management. Though the biologic era has provided a large armamentarium to treat uveitis, ongoing challenges and cases of recalcitrant uveitis remain, posing a challenge to internal medicine physicians. This comprehensive review aims to construct an updated summary on the existing evidence pertaining to the use of biologic agents in the treatment of uveitis. Methods include a systematic search for studies between 2000 and 2018 using PubMed, EMBASE, Ovid MEDLINE and Cochrane libraries.

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“…Data mainly come from published case series in adults and provide some successful results in the treatment of anterior uveitis, even in case of severe refractory disease to TNFα inhibitors. 10 Here we describe our experience with TCZ for treatment of JIA-associated uveitis at a paediatric rheumatology referral centre, reporting the cases of two adolescents with severe and first-line therapy-refractory uveitis associated with positive serum antinuclear antibodies (ANA) oligoarticular JIA, who responded favourably to TCZ (Table 1). The first paediatric report of the successful use of tocilizumab for otherwise refractory JIA-associated uveitis was described by Knoll et al 8 in 2012.…”

Section: What Is K Nown and S Tudy Objec Tivementioning

confidence: 99%

Tocilizumab for refractory uveitis associated with juvenile idiopathic arthritis: A report of two cases

et al. 2019

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Summary What is known and the objective Low‐grade evidence supports the use of newer biologics for otherwise refractory juvenile idiopathic arthritis (JIA)‐associated uveitis, such as tocilizumab. Case summary This report details the cases of two adolescents whose severe JIA‐associated uveitis was unresponsive to the first‐line therapeutic approach. Tocilizumab therapy led to the remission of uveitis after a mean time of 3 weeks, and methotrexate was safely discontinued 1.5 years later. What is new and conclusion To our knowledge, these are the first reports of successful methotrexate withdrawal during tocilizumab treatment of JIA‐associated uveitis. The administration of tocilizumab without methotrexate could be considered in patients with JIA‐associated uveitis unresponsive to conventional therapy.

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Anti–Interleukin‐6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis–Associated Uveitis Refractory to Anti–Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty‐Five Patients

Abstract: TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.

Cited by 144 publications

References 43 publications

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis–Associated Uveitis

The use of biologic agents in the management of uveitis

Tocilizumab for refractory uveitis associated with juvenile idiopathic arthritis: A report of two cases

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