Methotrexate Therapy May Prevent the Onset of Uveitis in Juvenile Idiopathic Arthritis

Papadopoulou, Charalampia; Kostik, Mikhail M.; Böhm, M.; Nieto‐González, Juan Carlos; González-Fernández, María; Pistorio, Angela; Martini, Alberto; Ravelli, Angelo

doi:10.1016/j.jpeds.2013.03.047

Cited by 58 publications

(38 citation statements)

References 16 publications

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“…It has been hypothesized that ETN may not directly cause the development of uveitis, but the discontinuation of MTX upon successful arthritis control may pose the patient at risk [38]. Recent data have shown that MTX may prevent the onset of uveitis in children with JIA [39, 40]. Nevertheless, many patients who had ETN discontinued for uveitis were likely switched to adalimumab and infliximab, which are nowadays recommended as second-line therapeutic option among patients with JIA and uveitis [41].…”

Section: Discussionmentioning

confidence: 99%

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

et al. 2016

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BackgroundData from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN).MethodsIn 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment.Results1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child’s illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis.ConclusionsAround half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity.

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Section: Discussionmentioning

confidence: 99%

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

et al. 2016

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“…Children with ERA are at risk for the acute anterior uveitis characteristic of adults with SpA [107]; treatment of both types of uveitis are similar. Methotrexate appears to be the most widely used first-line agent in addition to topical CS, and its use may even prevent onset of uveitis [108]. Among the biologics, the TNFi have been the most widely used [109], although the monoclonal antibodies are more effective than etanercept [110].…”

Section: Reviewmentioning

confidence: 99%

Treatment of juvenile idiopathic arthritis: a revolution in care

2014

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A generation ago, children with arthritis faced a lifetime of pain and disability. Today, there are a multitude of treatment options, including a variety of biologics targeting key cytokines and other inflammatory mediators. While non-steroidal anti-inflammatory drugs and corticosteroids were once the mainstay of therapy, they are now largely used as bridge or adjunctive therapies. Among the conventional disease-modifying anti-rheumatic drugs, methotrexate remains first-line therapy for most children with juvenile idiopathic arthritis (JIA) due to its long track record of safety and effectiveness in the management of peripheral arthritis. Sulfasalazine and leflunomide may also have a secondary role. The tumor necrosis factor inhibitors (TNFi) have shown tremendous benefit in children with polyarticular JIA and likely in enthesitis-related arthritis and psoriatic JIA as well. There may be additional benefit in combining TNFi with methotrexate. Abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear. For the treatment of systemic JIA, while the TNFi are of less benefit, blockade of interleukin-1 or interleukin-6 is highly effective. Additionally, interleukin-1 blockade appears to be effective treatment of macrophage activation syndrome, one of the most dangerous complications of JIA; specifically, anakinra in combination with cyclosporine and corticosteroids may obviate the need for cytotoxic approaches. In contrast, methotrexate along with the TNFi and abatacept are effective agents for the management of uveitis, another complication of JIA. Overall, the biologics have demonstrated an impressive safety record in children with JIA, although children do need to be monitored for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of malignancy. Finally, there may be a window of opportunity during which children with JIA will demonstrate most optimal responses to aggressive therapy, underscoring the need for rapid diagnosis and initiation of treatment.

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“…Topical and oral corticosteroids, and methotrexate, are the most common initial therapies in paediatric uveitis and are effective in up to 73% patients . Corticosteroid therapy in children has many adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Changing biological disease modifying treatment for paediatric uveitis in the real world

Nguyen

Phan

et al. 2019

Clinical Exper Ophthalmology

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Importance Paediatric uveitis is a severe sight‐threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real‐world data on their use from Sydney, Australia. Background Traditionally corticosteroids and non‐biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes. Design Retrospective, chart review over an 8‐year period at a tertiary referral eye hospital. Participants A total of 27 paediatric uveitis patients treated with biological agents. Methods Chart review of demographic data and treatment outcomes. Main Outcome Measures Treatment efficacy (corticosteroid‐sparing effect, topical steroid cessation/reduction, reduction in systemic‐steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months. Results Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid‐sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction. Conclusions and Relevance Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.

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Methotrexate Therapy May Prevent the Onset of Uveitis in Juvenile Idiopathic Arthritis

Cited by 58 publications

References 16 publications

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

Treatment of juvenile idiopathic arthritis: a revolution in care

Changing biological disease modifying treatment for paediatric uveitis in the real world

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