Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis

Heiligenhaus, Arnd; Minden, Kirsten; Tappeiner, Christoph; Baus, H; Bertram, Bernd; Deuter, Christoph; Foeldvari, Ivan; Föll, D.; Frosch, Michael; Ganser, Gerd; Gaubitz, M.; Günther, Annette; Heinz, Carsten; Horneff, Gerd; Huemer, Christian; Kopp, I.; Lommatzsch, Claudia; Lutz, Thomas; Michels, H.; Neß, Thomas; Neudorf, Ulrich; Pleyer, Uwe; Schneider, M.; Schulze‐Koops, Hendrik; Thurau, Stephan; Zierhut, Manfred; Lehmann, Harald

doi:10.1016/j.semarthrit.2018.11.004

Cited by 75 publications

(73 citation statements)

References 149 publications

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“…It is not well defined whether ANA-positive idiopathic anterior uveitis can be treated like JIA-associated uveitis and whether responses to treatment are similar. In a recent therapy guideline, it was accepted that uveitis can take a very similar course in patients with JIA and those with ANA positivity but no JIA, and that these two groups should be treated in the same way [16]. This is in accordance with the recently published CARRA consensus treatment plans for anterior uveitis [20], but this concept relies on previous observations from a single, retrospective, monocentric study and with a limited number of patients [21].…”

Section: Introductionmentioning

confidence: 57%

“…Treatment for uveitis is mostly instituted with topical corticosteroids, and an escalation of therapy to diseasemodifying anti-rheumatic drugs (DMARDs) is required in patients not responding properly or who present a particularly severe disease course [15,16]. Populationbased studies recently determined that changes in treatment patterns, i.e., more frequent use of DMARDs, reduced uveitis prevalence [17], and improved outcome of uveitis [8,18].…”

Section: Introductionmentioning

confidence: 99%

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Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

et al. 2020

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Background: To analyze whether ANA-positive idiopathic anterior uveitis differs from JIA-associated uveitis concerning clinical course, response to treatment, and disease outcome. Methods: Prospective study of the National Paediatric Rheumatological Database (NPRD) including its uveitis addon module from the years 2002 to 2016. Cross-sectional data from the years 2002 to 2016 were analyzed. Patients with JIA-associated uveitis and with ANA-positive idiopathic anterior uveitis were included and the disease manifestation investigated in terms of uveitis characteristics and disease course. Results: Of the total cohort of 34,458 patients enrolled in the NPRD, including 3551 patients with uveitis, those with detailed uveitis documentation were taken into account: 62 ANA-positive patients with idiopathic anterior uveitis (group 1), 688 patients with initial uveitis diagnosis after JIA onset (group 2), and 61 JIA patients with initial uveitis diagnosis before arthritis onset (group 3). Anterior uveitis was documented in 100%, 94%, and 80% of patients and with insidious onset of uveitis flare in 50%, 70.9%, and 56.1% each in groups 1, 2, and 3, respectively. Use of topical or systemic corticosteroids and conventional synthetic or biological DMARDs did not significantly differ between the patient groups, either at the initial or the 2-year follow-up (2-FU) visits (mean 2 years, each p > 0.05). At 2-FU, uveitis inactivity was achieved in 64.7%, 55.8%, and 61.5% of patients in groups 1, 2, and 3 (p > 0.05). Uveitis-related complications were more frequent at the initial visit and at 2-FU in groups 1 and 3, as compared to group 2. Conclusions: ANA-positive idiopathic uveitis and JIA-associated uveitis do not significantly differ concerning clinical course of uveitis, treatment, and response to corticosteroids and DMARDs.

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Section: Introductionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

et al. 2020

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“…31 The paucity of clinical trials for paediatric uveitis combined with the availability of potential treatments through use in other rheumatic diseases has led to many immunosuppressive drugs being prescribed for paediatric uveitis and included in treatment guidelines with little evidence. 32 A strength of this study is the incorporation of the Simon design to identify molecules for further clinical study in patients with paediatric uveitis, with low risk to participants, and to enable the gathering of evidence and publication of results in a more systematic way than in case series and openlabel studies. Safety results were consistent with the known safety profile of intraven ous tocilizumab, with the exception of injection site reactions.…”

Section: Resultsmentioning

confidence: 99%

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Ramanan

Dick

Guly

et al. 2020

The Lancet Rheumatology

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Background Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors. Methods This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23). Findings 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0•11). Safety results were consistent with the known safety profile of tocilizumab. Interpretation The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options.

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“…With ADA, the risk for uveitis was lower but did not reach statistical significance. ADA is recommended for treatment of JIA-related uveitis after its efficacy was demonstrated in a randomized controlled trial (15,16). The risk for uveitis flare was higher in patients receiving TNFi antibodies (ADA, GOL, INF).…”

Section: Discussionmentioning

confidence: 99%

Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long‐Term Safety Data from the German BIKER Registry

Klein

Becker

Minden

et al. 2019

ACR Open Rheumatology

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Objective. Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long-term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long-term safety with regard to AE of special interest (AESI) was compared between different biologics.Methods. Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.Results. A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2-15, and RR 4.7, 95% CI 1.8-12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.Conclusion. Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long-term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.

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Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis

Cited by 75 publications

References 149 publications

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long‐Term Safety Data from the German BIKER Registry

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