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Research ArticlePediatric Rheumatology
Open Access

Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis

Roberta Berard, Hon Yan Ng, Andrea Human, David Piskin, Muhammed Dhalla, Chloe Gottlieb, Michelle Batthish, Gaëlle Chédeville, Christina Forest, Eric Fortin, Jane Gardiner, Kerstin Gerhold, Andre Jastrzebski, Bianca Lang, Paivi M.H. Miettunen, Sabrina Morgenstern, Marie-Paule Morin, Alan Rosenberg, Dax G. Rumsey, Carlos E. Solarte, Nasrin Tehrani, Karen Watanabe Duffy, Jordi Pardo Pardo, Glen S. Hazlewood and Deborah M. Levy
The Journal of Rheumatology March 2023, 50 (3) 390-399; DOI: https://doi.org/10.3899/jrheum.220261
Roberta Berard
1R. Berard, MD, MSc, Division of Rheumatology, and Department of Pediatrics, Western University, London, Ontario;
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  • For correspondence: roberta.berard@lhsc.on.ca
Hon Yan Ng
2H.Y. Ng, MD, Division of Pediatric Rheumatology, and Department of Pediatrics, University of Alberta, Edmonton, Alberta;
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Andrea Human
3A. Human, MD, MSc, Division of Rheumatology, BC Children’s Hospital, University of British Columbia, Vancouver, British Columbia;
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David Piskin
4D. Piskin, MSc, Lawson Health Research Institute, London, Ontario;
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Muhammed Dhalla
5M. Dhalla, MD, Division of Pediatric Rheumatology, and Department of Pediatrics, University of Calgary, Calgary, Alberta;
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Chloe Gottlieb
6C. Gottlieb, MD, University of Ottawa Eye Institute and Department of Ophthalmology, Faculty of Medicine, University of Ottawa, and The Ottawa Hospital Research Institute, Ottawa, Ontario;
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Michelle Batthish
7M. Batthish, MD, MSc, Division of Rheumatology, Department of Pediatrics, McMaster University, Hamilton, Ontario;
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Gaëlle Chédeville
8G. Chédeville, MD, Division of Rheumatology, Department of Pediatrics, McGill University Health Center, Montreal, Quebec;
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Christina Forest
9C. Forest, BSc, Caregiver Champion, Montreal, Quebec;
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Eric Fortin
10E. Fortin, MD, Department of Ophthalmology, University of Montreal, Montreal, Quebec;
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Jane Gardiner
11J. Gardiner, MD, Department of Ophthalmology and Vision Science, University of British Columbia, Vancouver, British Columbia;
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Kerstin Gerhold
12K. Gerhold, MD, Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada, and Mississippi Center for Advanced Medicine, Madison, Mississippi, USA;
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Andre Jastrzebski
13A. Jastrzebski, MD, Department of Ophthalmology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba;
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Bianca Lang
14B. Lang, MD, Dalhousie University and IWK Health Centre, Halifax, Nova Scotia;
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Paivi M.H. Miettunen
15P.M.H. Miettunen, MD, Division of Rheumatology, University of Calgary and Alberta Children’s Hospital, Calgary, Alberta;
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Sabrina Morgenstern
16S. Morgenstern, BA, BEd, Caregiver Champion, Saskatoon, Saskatchewan;
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Marie-Paule Morin
17M.P. Morin, MD, PhD, Division of Immunology and Rheumatology, Department of Pediatrics, University of Montreal, Montreal, Quebec;
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Alan Rosenberg
18A. Rosenberg, MD, Division of Rheumatology, Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan;
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Dax G. Rumsey
19D.G. Rumsey, MD, MSc, Department of Pediatrics, University of Alberta, Edmonton, Alberta;
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Carlos E. Solarte
20C.E. Solarte, MD, Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta;
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Nasrin Tehrani
21N. Tehrani, MD, Division of Ophthalmology, The Hospital for Sick Children and University of Toronto, Toronto, Ontario;
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Karen Watanabe Duffy
22K.W. Duffy, MD, Children’s Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario;
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Jordi Pardo Pardo
23J. Pardo Pardo, MSc, Cochrane Musculoskeletal, Faculty of Medicine, University of Ottawa, Ottawa, Ontario;
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Glen S. Hazlewood
24G.S. Hazlewood, MD, PhD, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta;
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Deborah M. Levy
25D.M. Levy, MD, MS, Division of Rheumatology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
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Abstract

Objective To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA).

Methods Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion.

Results The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo.

Conclusion Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

Key Indexing Terms:
  • chronic anterior uveitis
  • evidence-to-decision framework
  • GRADE-ADOLOPMENT
  • guidelines
  • juvenile idiopathic arthritis

Chronic, asymptomatic anterior uveitis occurs in up to 20% of children with juvenile idiopathic arthritis (JIA) and can be associated with significant morbidity, including permanent vision loss.1 However, early detection of ocular inflammation through regular ophthalmic screening with prompt and appropriate treatment can maintain good vision and prevent complications despite the diagnosis of a potentially sight-threatening uveitis. Female sex, young age at onset of JIA (age < 7), and antinuclear antibody (ANA) positivity are risk factors for JIA-associated uveitis.2,3 The cumulative incidence of new-onset uveitis during the first 5 years after JIA diagnosis was 13.9%, which supports the need for vigilant uveitis screening during this time frame.3 Care for patients with JIA-associated uveitis requires a collaborative approach between rheumatology and ophthalmology, and in some cases, other eye care providers for screening. Treatment for uveitis can be complex and may require combinations of topical and/or systemic therapies, with frequent healthcare visits and treatment changes.

In 2019, the American College of Rheumatology (ACR) and the Arthritis Foundation (AF) collaborated to develop and publish guidelines for the screening, monitoring, and treatment of JIA-associated uveitis.4 These were the first North American guidelines to address JIA-associated uveitis and to propose an approach to using systemic immunosuppressive therapy for uveitis that is dependent on or refractory to topical glucocorticoids (GCs). Long-term use of topical GCs should be avoided to reduce their potential side effects, including increased intraocular pressure and cataract formation.5,6 Despite a relatively uniform approach to treatment, only 3 published controlled trials specifically examined systemic therapies in JIA-associated uveitis.7-9 Regulatory body approval for therapeutics is challenging and lacking because of the paucity of evidence. The ACR/AF guidelines provide an opportunity for education and advocacy to local, provincial, and national regulatory bodies and payers to improve access to advanced therapies. In Canada, where health care is a provincial rather than federal jurisdiction, there is variation in access to rheumatologists and ophthalmologists with expertise in uveitis and to biologic therapies. The availability of Canadian-specific, expert consensus guidelines for monitoring and managing JIA-associated uveitis will help ensure optimal care is standardized nationwide.

The ACR/AF guidelines used the rigorous Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology, informed by a consensus process with rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values. These guidelines were the first to address screening, monitoring, and treatment and the only to use GRADE methodology, and were therefore selected as a baseline framework. We used the GRADE-ADOLOPMENT method10 to consider Canadian contextual differences, including patient preferences, cost/resource considerations, and feasibility of implementation. The adolopment method provides an efficient framework to capitalize on previous work and reduce redundancy. The development of evidence-to-decision (EtD) tables for each recommendation provide a transparent process for judgement of the evidence and context-specific considerations, and is then followed by adoption, adaptation, or de novo development of recommendations. Adoption is the use of an existing, trustworthy recommendation without modification of the original recommendation; adaptation involves identifying the pertinent healthcare questions, searching for existing guidelines that addressed those questions, critically appraising them, and deciding whether to accept or modify selected recommendations; and de novo development of recommendations involves formulating new questions and seeking to answer them in a recommendation not included in original guidelines.10

This work represents the first set of Canadian JIA-associated uveitis guidelines, and the first Canadian Rheumatology Association (CRA) guideline to apply the GRADE-ADOLOPMENT framework. Using this methodology allowed us to develop guidelines applicable to the Canadian context considering cost, equity, and access.

METHODS

A Canadian JIA-associated uveitis working group was assembled, including 14 pediatric rheumatologists representing 13 of 14 Canadian academic centers plus 1 community-based pediatric rheumatologist and 1 trainee. Six geographically diverse ophthalmologists with a special interest and/or subspecialty training in uveitis joined the working group in addition to 3 uveitis parent/patient champions. The CRA guidelines committee chair, a Cochrane Musculoskeletal representative, and a research associate were nonvoting members of the working group. All working group members completed the International Committee of Medical Journal Editors conflict of interest form prior to the start of the project.

Following the GRADE-ADOLOPMENT stages:

1. An updated systematic literature review was completed using the same search terms as the ACR/AF guidelines (further referred to as the source guideline). The systematic review was conducted by an electronic search of OVID MEDLINE, Embase, PubMed, and the Cochrane Library from October 13, 2017 (end date of the ACR/AF search), to February 6, 2020. In addition, literature reviews for equity, patient preferences, and economics were completed for this patient population. For each article, 2 working group members were assigned for data extraction and summary-of-finding (SoF) tables were completed (Supplementary File S1, available with the online version of this article). The quality of evidence was rated as high, moderate, low, or very low, accounting for risk of bias, inconsistency, indirectness, imprecision, and other considerations as per the GRADE recommendations.11

2. The recommendations from the source guidelines were reviewed by 2 members of the working group. Member pairs were selected to ensure geographic diversity and pairing of a rheumatologist with an ophthalmologist, 2 rheumatologists, or 2 ophthalmologists, depending on the context of each recommendation. Each pair reviewed the source guideline PICO (Population – Intervention – Control – Outcomes) question, selected articles, SoF tables, and the recommendation. Each recommendation also was considered using a Table of Equity Filters developed by the Quality Care Committee of the CRA that included the following data: Indigenous, rural/remote location, refugee, and low socioeconomic status/homelessness.12,13 Using these sources, an EtD table14 was developed for each recommendation (Supplementary File S2, available with the online version of this article) by the pair. EtD tables included the Summary of Evidence about the benefits and harms of the interventions being considered, in addition to information about the importance of the problem (eg, baseline risk), patients’ values and preferences, resource use and costs, feasibility, acceptability, and potential impact on health equity of recommending specific intervention options in the context of the healthcare setting and affected stakeholders.

EtDs were reviewed (RB and DML) and discussed with the methodologists (GSH and JPP), with feedback and edits performed by each member pair.

3. A web survey was completed by all working group members to assess agreement on the source guideline recommendations in a Canadian context. Questions for each recommendation included the following: (1) Do you agree to adopt this recommendation as presented? (2) Do you agree to adopt this recommendation with a change in wording based on evidence/additional considerations as presented by the EtD table? (3) Are there any other considerations to add for this recommendation, such as a Canadian context of cost, access, or vulnerable populations? (4) Does this recommendation need to be discussed at the webinar? All respondents were provided with the accompanying finalized EtD (Supplementary File S2, available with the online version of this article) for review with the equity filters to be incorporated into their survey responses. All recommendations with > 50% of survey respondents indicating disagreement/discussion required were reviewed at a virtual meeting.

4. The virtual meeting held in August 2020 was facilitated by nonvoting advisors (GSH and JPP). An in-person consensus meeting was not possible because of the coronavirus disease 2019 (COVID-19) pandemic. EtDs with recommendations were presented, discussed, and voted upon at the meeting. Then, the decision was made for each recommendation to be adopted, adapted, or developed de novo in order to reach the final set of recommendations. Consensus was set a priori at 80% agreement of voting panel members. However, there was 100% agreement on all adapted and newly developed recommendations.

Ethics. Research Ethics Board approval was not required for this project.

RESULTS

The literature searches retrieved 410 citations for JIA-associated uveitis and 554 articles for equity, patient preferences, and economics after removing duplicates (Figure). Full-length articles were reviewed, data abstracted, and evidence graded using the 19 PICO questions from the source guideline. The screening process was done by 2 independent reviewers (DP and HYN) and disagreements were resolved by a third reviewer (RB or DML). Twenty-two additional articles were identified. From these, SoF tables (n = 26) for observational studies and GRADE tables (n = 2) for clinical trials were developed and updates to the ACR tables were produced (Supplementary File S1, available with the online version of this article). The available evidence was of low quality for all PICO questions, mainly because of the lack of evidence and the indirectness of the evidence. Most articles were based on observational studies, which are considered low quality by the GRADE system. Implementation in rural and remote areas, Indigenous populations, low socioeconomic status, and access to treatments were considerations applied to all recommendations.

Figure.
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Figure.

Summary of search strategies to identify key articles.

The terms, definitions, medication interventions, and critical/important outcomes as defined by the ACR/AF guidelines4 were used during the development of the CRA-GRADE-ADOLOPMENT recommendations.

How to interpret the recommendations. The strength of a recommendation is expressed as either strong (“the guideline panel strongly recommends…”) or conditional (“the guideline panel conditionally recommends…”); the interpretations are outlined in Table 1.

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Table 1.

Interpretation of strong and conditional recommendations.

Results from the web survey identified agreement to adopt 13 of the source recommendations by the Canadian Uveitis Working Group as presented (Table 2). The remaining 6 were discussed in detail at the virtual meeting attended by 75% (15/20) of the working group, 3 parent/patient representatives, and 2 nonvoting advisors (GSH and JPP). The 7 recommendations requiring significant revision pertained to screening (n = 1 recommendation adapted) and treatment (n = 6; Table 2). Following the virtual working group discussion, 5 recommendations were adapted (ACR/AF recommendations 1, 8, 9, 13, and 15), 2 recommendations were removed (ACR/AF recommendations 10 and 11), and 1 was developed de novo (new recommendation 4). For the working group members who could not attend the virtual meeting, feedback and comments were incorporated, and 100% consensus was achieved from the group discussion for the 7 recommendations discussed below. The revised recommendations are as follows:

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Table 2.

Recommendations for ophthalmic screening, ophthalmic monitoring, and treatment of children with JIA-associated uveitis, including modifications by the CRA Uveitis Working Group.

Recommendation 1 (ACR/AF recommendation 1 adapted). In children and adolescents with JIA at high risk of developing chronic anterior uveitis (CAU), ophthalmic screening at least every 3 months for the first 4 years is conditionally recommended over screening at a different frequency. Patients with newly diagnosed disease should be screened as early as possible after diagnosis, within the first 1 to 3 months if asymptomatic (conditional recommendation, very low certainty of evidence).

Remarks: When deciding on the frequency of ophthalmic monitoring, close collaboration and communication between rheumatologists and ophthalmologists is crucial. The addition of “at least every 3 months” encompasses those with vision-threatening disease. The group also discussed adding “for at least the first 4 years of disease” to be reflective of risk for development of uveitis based on significant risk factors. These are well described and include young age at onset of JIA (< 7 years), oligoarticular subtype, female sex, and a positive ANA test.3,15 The group agreed that the recommendation should include timing to first eye examination and that this information be shared with caregivers. This was not addressed in the ACR/AF recommendations. Caregiver/patient understanding of the importance of timing of examination was noted to be critical given the asymptomatic nature of uveitis that can lead to a delay in diagnosis if initial and ongoing regular screening is delayed.16 The expert consensus discussion agreed the time to first examination to be within 1 to 3 months of diagnosis regardless of the geographic location of the patient. The working group acknowledged that this may be challenging for patients living in rural/remote areas who must travel to access eye care, and for those requiring funding for travel to eye care. A detailed discussion occurred around who can and should perform ophthalmic screening, with differing opinions and additional considerations put forth from geographically diverse centers. Given the large geographic area that pediatric rheumatology/ophthalmology centers serve and the lack of a sufficient number of ophthalmologists in many urban centers, timely access can be a concern. Ophthalmic screening is optimally completed by an ophthalmologist but could include another eyecare provider if timely access is otherwise not possible. Eye examination should be verified by an ophthalmologist with uveitis expertise when the opportunity comes available.

Recommendations 2 and 3 (ACR/AF recommendation 8 and 9 adapted). For recommendation 2, in children and adolescents with JIA and CAU requiring more than 2 drops per day of prednisolone acetate 1% (or equivalent) at 3 months after the start of uveitis treatment, and not on systemic therapy, adding systemic therapy to taper topical GCs is conditionally recommended over not adding systemic therapy and maintaining on topical GCs only (conditional recommendation, very low certainty of evidence).

For recommendation 3, in children and adolescents with JIA and CAU requiring more than 2 drops per day of prednisolone acetate 1% (or equivalent) for at least 3 months and on systemic therapy for uveitis control, changing or escalating systemic therapy is conditionally recommended over maintaining current systemic therapy (conditional recommendation, very low certainty of evidence).

Remarks: The adapted recommendations differ from the ACR/AF guidelines, which indicate a threshold of 1 to 2 drops per day for the addition/change/escalation of systemic therapy. Review of the evidence for this recommendation revealed published data showing that there is a risk of ocular complications when more than 2 drops of topical GCs are used per day.17,18 A robust discussion occurred regarding the threshold for escalation to systemic therapy, and while evidence is limited, both rheumatologists and ophthalmologists agreed the risk for complications related to topical GC therapy is increased with long-term use of 3 or more drops per day.17 This recommendation is also in agreement with the Australia- and New Zealand–based expert consensus JIA-Uveitis Working Group recommendations, which support the threshold of greater than 2 drops per day.19 The decision to escalate therapy should be individualized and done using a shared decision-making framework; in some cases where noncompliance or significant burden is associated with topical drops, escalation may be considered when 1 to 2 drops per day is required.

The group unanimously agreed upon a maximum 3-month interval of monitoring uveitis, at which point adding systemic therapy should be considered. The group discussed the term “active” to which the group agreed also includes “steroid dependent.” Active uveitis includes steroid-dependent uveitis that appears controlled on more than 2 drops of topical steroid per day.

Recommendation 4 (developed de novo). In children and adolescents with JIA and CAU who are initiating systemic treatment for CAU, methotrexate (MTX) is conditionally recommended as the first-line disease-modifying antirheumatic drug (DMARD; conditional recommendation, very low certainty of evidence).

Remarks: The working group developed a conditional recommendation for MTX use as the first-line DMARD. The ACR/AF guidelines did not have a specific recommendation for a first-line systemic therapy although it is implied in recommendation 10, which conditionally recommends subcutaneous over oral MTX in patients starting systemic therapy. Both the expert consensus-based Single Hub and Access Point for Paediatric Rheumatology in Europe (SHARE),20 and Australia/New Zealand19 groups have a specific recommendation for MTX as the first-line systemic therapy. MTX has demonstrated safety and efficacy for the treatment of JIA-associated uveitis in several retrospective studies in doses of 15 mg/m2 (alternatively up to 1 mg/kg) to a maximum of 25 mg weekly.21-27 These results have been confirmed in subsequent systematic reviews.28-30 Two other consensus treatment guidelines also support MTX as the first-line systemic therapy for JIA-associated uveitis.20,31 Other nonbiologic DMARD (nbDMARD) therapies, including mycophenolate mofetil (MMF), azathioprine, and cyclosporine, have been used in uveitis with variable success,32-36 and these drugs are most often tried in MTX-refractory cases. The studies include very small numbers of patients, restricting the quality of evidence and the evidence of efficacy. Overall, the evidence for MTX is more robust than for other conventional DMARDs, despite the generally limited quality of studies available. Thus, MTX is conditionally recommended as the first-line systemic therapy for JIA-associated uveitis.

The source guidelines conditionally recommend subcutaneous over oral MTX (ACR/AF recommendation 10) because of data suggesting increased bioavailability of the subcutaneous formulation at doses greater than 15 mg/m2.37,38 The Methotrexate Advice and Recommendations on Juvenile Idiopathic Arthritis31 consensus recommendations align with this recommendation, as do the Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for Juvenile Idiopathic Arthritis–Associated and Idiopathic Chronic Anterior Uveitis.39 However, there is a lack of high-quality evidence demonstrating clinical superiority of subcutaneous over oral MTX in JIA-associated uveitis. The dose, presence of or potential for complications, patient/caregiver preference, patient/caregiver comfort level with injections, and provincial health authority criteria for funding biologics following MTX failure (so as not to delay escalation of therapy) should be considered when deciding on the initial route of administration of MTX for children with JIA-associated uveitis.

Recommendation 11 from the ACR/AF guidelines provides a conditional recommendation for starting dual therapy over MTX alone, but the working group favored monotherapy with MTX. There is no direct evidence for one approach over the other, and no evidence about the risk of complications and safety of dual therapy compared to the safety of MTX monotherapy. The working group had concerns about the lack of access to tumor necrosis factor inhibitors (TNFis) as a first-line therapy in Canada for treatment of JIA-associated uveitis.

The ophthalmologists noted that there are no standardized definitions for severe or sight-threatening complications. The ACR/AF defines severe as “the presence of ocular structural complications due to uveitis, or complications of topical steroid therapy.” It was noted that severe uveitis is not necessarily more difficult to treat than mild uveitis because disease severity does not equal disease chronicity; however, presence of complications of uveitis, such as posterior synechiae or cataracts are indicators of a poor visual outcome for patients with JIA-associated uveitis.1 The group, therefore, decided to remove the term “severe.” Thus, recommendation 11 from the source guidelines was removed from the current guidelines.

Recommendation 5 (ACR/AF recommendation 13 adapted). In children and adolescents with JIA and active CAU who have an inadequate response to one monoclonal antibody TNFi at standard JIA dosing, optimizing the dose and/or frequency of the current TNFi is conditionally recommended over switching to another monoclonal antibody TNFi (conditional recommendation, very low certainty of evidence).

Remarks: There are no randomized controlled trials for comparisons of one monoclonal TNFi vs another for the treatment of JIA-associated CAU. The working group considered that the ACR/AF wording of “above standard” dosing may have equity implications with access to “above standard” dosing potentially differing by treating site or based on reimbursement issues, both of which can cause anxiety for patients/caregivers. Product monograph dosing for adalimumab (ADA) includes dosing of 40 mg subcutaneously every 2 weeks for patients weighing more than 30 kg; however, to achieve maximal clinical benefit patients may be treated with 40 mg subcutaneously weekly, with no significant increase in reported adverse effects.40,41 Decreasing the interval of infliximab to less than every 4 weeks and/or increasing the dose to more than 10 mg/kg can be considered. Older case series literature supports its safety.42 Patient/caregiver advisors also note that adjustments to current medication regimens would be preferred rather than introducing a new medication unless there are clear benefits to doing so (conditional recommendation, very low certainty of evidence).

Recommendation 6 (ACR/AF recommendation 15 adapted). In children and adolescents with JIA and active CAU who have failed MTX and 2 monoclonal antibody TNFis at optimized doses, the use of abatacept (ABA) or tocilizumab (TCZ) as biologic DMARD (bDMARD) options are conditionally recommended over nbDMARD options (MMF, leflunomide, or cyclosporine; conditional recommendation, very low certainty of evidence).

Remarks: There is no evidence to guide treatment of CAU in patients who have failed 2 monoclonal TNFis. The ACR/AF recommendations do not specify a preference of bDMARD vs nbDMARD options. The working group’s expert opinion with review of observational data conditionally recommended a bDMARD such as TCZ or ABA9,43-47 over a nbDMARD in patients with refractory CAU. Other biologic agents investigated include daclizumab and rituximab48,49 and an alternative monoclonal TNFi (golimumab).50,51 All studied biologic therapies do demonstrate some benefit in patients refractory to conventional therapy. Of note, in patients refractory to monoclonal TNFi, literature review reveals no direct evidence of the effects of low drug trough levels or the development of antidrug antibodies on the clinical efficacy of biological agents in patients with uveitis. The SHARE20 group based their recommendations on findings in other clinical settings, concluding that in cases of loss of efficacy over time, consideration should be given to testing for antidrug antibodies and drug trough levels.52-54 If the patient has no antibodies, but has low trough levels, increasing the dose or shortening the interval may be an option.41

DISCUSSION

Results from our CRA Uveitis Working Group differed from the ACR/AF recommendations in some aspects of screening and treatment for JIA-associated CAU when considered in the Canadian context. These differences include: (1) the timing to first ophthalmic screening, (2) threshold of topical GC for escalation to systemic treatment (> 2 drops/day of prednisolone acetate 1% for > 3 months), (3) initial use of biologics favoring a step-up approach (with MTX conditionally recommended as a first-line DMARD) because of a lack of evidence but also because of access concerns to bDMARDs as a first-line therapy, (4) removal of the recommendation for use of subcutaneous vs oral MTX because of a lack of evidence, (5) modification of the recommendation for increasing the TNFi from “above standard dose and/or frequency” to “optimize” dose over TNFi switching, and (6) recommendation for the use of biologic over nonbiologic therapies for patients failing MTX and TNFi therapies.

The 2019 ACR/AF guidelines provide guidance on the screening, monitoring, and treatment with GC, nbDMARDs, and bDMARDs for CAU, as well as the education and treatment of children with or at risk of developing acute anterior uveitis. The guidelines were conducted using a rigorous GRADE methodology and the voting panel included pediatric rheumatologists, ophthalmologists, and adult patients with JIA. A caregiver and patient panel reviewed the collated evidence and provided input on their values and preferences in a separate voting meeting. Overall, the quality of evidence was very low, and most recommendations were conditional; however, the guidelines fill an important clinical gap in the care of children with JIA-associated uveitis.

Given the rigorous nature of the development of the ACR guidelines, recency of publication, and similarities in our medical systems, the GRADE-ADOLOPMENT approach was chosen over duplication of a GRADE methodology framework for the current project. Across the United States and Canada, we have similar challenges with access to medications, rheumatologists, and ophthalmologists. Thus, the ACR/AF guidelines are largely applicable to the Canadian context. However, a few important differences exist, including the 10 provincially regulated and 3 territorially regulated public and private payment models for medication, and hence there is varying access to biologic agents for the treatment of JIA-associated CAU.55 Also differing from the US is federally regulated coverage by the Non-Insured Health Benefits program for First Nations and Inuit populations. Further, access to pediatric rheumatology and ophthalmology care with expertise in uveitis varies greatly across the country. There is approximately 1 rheumatologist per 75,000 children in Canada56 but there are only 3 ophthalmologists per 100,000 population34 in Canada, with a far smaller number having expertise in uveitis in the pediatric patient population.57 Additionally, the density of pediatric rheumatologists and ophthalmologists is much higher in certain urban centers than in many other parts of Canada. Equitable access to the optimal shared care model for JIA-associated CAU can be affected by distance to an urban center, with some patients living in remote areas having to travel more than 2000 km to their treating center. In some instances, this may require involvement of other eyecare providers for screening.

The GRADE-ADOLOPMENT approach provides a structured means to selectively combine adoption, adaptation, and de novo development of guideline recommendations. The most important first step of this process was to conduct an updated systematic review that was used by the guideline panel. Further, efficiency was optimized by using the EtD framework, which provides transparency in the decision-making process and in the considerations made by the guideline panel when formulating recommendations.

In Canada, we do not have national pharmacare and thus significant provincial differences in access to biologics remain. Off-label use of biologics can be challenging to access because of high cost and lack of compassionate drug supply. The introduction of biosimilars may improve equitable access to therapies. Across the country, biosimilar drugs and availability is changing rapidly; for example, as of May 2021 there are 4 new ADA biosimilars available with Health Canada indications for pediatric uveitis. In some provinces, private insurance plans follow guidance from the public reimbursement standards and uniquely cover biosimilar drugs. Over the past 2 years some provinces have moved to nonmedical switching from the originator biologic to the biosimilar to promote savings of healthcare dollars.

The CRA Uveitis Working Group, comprising pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient/caregiver representatives, and methodology advisors, completed adolopment of the ACR/AF recommendations in a relatively short time, less than 1 year of effective time spent, and at low cost. An additional strength of this work is the incorporation of updated evidence. Judgments of the Canadian Uveitis Working Group did not markedly differ in the strength and direction of the recommendations, and as such, the majority of the source recommendations were adopted with minor alterations. Moving forward, we recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines with all supporting materials that were developed using a transparent process is available. The CRA JIA-associated CAU guidelines provide Canadian contextual considerations for optimal shared uveitis care, supporting equitable access to care and treatment.

ACKNOWLEDGMENT

We would like to acknowledge CRA team members including Sue Ranta for her administrative assistance for this project and Kevin Baijnauth for survey development and deployment, as well as the CRA Board for supporting this work. We would also like to acknowledge Amy Turner, Senior Director, Quality, ACR, for her administrative review, and the Canadian Ophthalmological Society Board for their endorsement of our recommendations.

Footnotes

  • The authors declare no conflicts of interest relevant to this article.

  • Accepted for publication July 21, 2022.
  • Copyright © 2023 by the Journal of Rheumatology

This is an Open Access article, which permits use, distribution, and reproduction, without modification, provided the original article is correctly cited and is not used for commercial purposes.

REFERENCES

  1. 1.↵
    1. Haasnoot AJ,
    2. Vernie LA,
    3. Rothova A, et al
    . Impact of juvenile idiopathic arthritis associated uveitis in early adulthood. PLoS One 2016;11:e0164312.
  2. 2.↵
    1. Saurenmann RK,
    2. Levin AV,
    3. Feldman BM,
    4. Laxer RM,
    5. Schneider R,
    6. Silverman ED
    . Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis. Arthritis Rheum 2010;62:1824-8.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Lee JJY,
    2. Duffy CM,
    3. Guzman J, et al; ReACCh-Out Investigators
    . Prospective determination of the incidence and risk factors of new-onset uveitis in juvenile idiopathic arthritis: the research in arthritis in Canadian Children Emphasizing Outcomes cohort. Arthritis Care Res 2019;71:1436-43.
    OpenUrl
  4. 4.↵
    1. Angeles-Han ST,
    2. Ringold S,
    3. Beukelman T, et al
    . 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res 2019;71:703-16.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Musson DG,
    2. Bidgood AM,
    3. Olejnik O
    . An in vitro comparison of the permeability of prednisolone, prednisolone sodium phosphate, and prednisolone acetate across the NZW rabbit cornea. J Ocul Pharmacol 1992;8:139-50.
    OpenUrlPubMed
  6. 6.↵
    1. Slabaugh MA,
    2. Herlihy E,
    3. Ongchin S,
    4. van Gelder RN
    . Efficacy and potential complications of difluprednate use for pediatric uveitis. Am J Ophthalmol 2012;153:932-8.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Ramanan AV,
    2. Dick AD,
    3. Jones AP, et al; SYCAMORE Study Group
    . Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis. N Engl J Med 2017;376:1637-46.
    OpenUrlCrossRefPubMed
  8. 8.
    1. Quartier P,
    2. Baptiste A,
    3. Despert V, et al; ADJUVITE Study Group
    . ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Ann Rheum Dis 2018; 77:1003-11.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Ramanan AV,
    2. Dick AD,
    3. Guly C, et al; APTITUDE Trial management Group
    . Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial. Lancet Rheumatol 2020;2:e135-41.
  10. 10.↵
    1. Schünemann HJ,
    2. Wiercioch W,
    3. Brozek J, et al
    . GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT. J Clin Epidemiol 2017;81:101-10.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Guyatt GH,
    2. Oxman AD,
    3. Vist GE, et al; GRADE Working Group
    . GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6.
    OpenUrlFREE Full Text
  12. 12.↵
    1. Barnabe C,
    2. Pianarosa E,
    3. Hazlewood G
    . Informing the GRADE evidence to decision process with health equity considerations: demonstration from the Canadian rheumatoid arthritis care context. J Clin Epidemiol 2021;138:147-55.
    OpenUrl
  13. 13.↵
    1. Pianarosa E,
    2. Hazlewood G,
    3. Thomas M,
    4. Hsiao R,
    5. Barnabe C
    . Supporting equity in rheumatoid arthritis outcomes in Canada: population-specific factors in patient-centered care. J Rheumatol 2021;48:1793-1802.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Alonso-Coello P,
    2. Oxman AD,
    3. Moberg J, et al; GRADE Working Group
    . GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ 2016;353:i2089.
  15. 15.↵
    1. Heiligenhaus A,
    2. Niewerth M,
    3. Ganser G,
    4. Heinz C,
    5. Minden K; German Uveitis in Childhood Study Group
    . Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines. Rheumatology 2007;46:1015-9.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Rypdal V,
    2. Glerup M,
    3. Songstad NT, et al
    . Uveitis in juvenile idiopathic arthritis: 18-year outcome in the population-based Nordic cohort study. Ophthalmology 2021;128:598-608.
    OpenUrl
  17. 17.↵
    1. Thorne JE,
    2. Woreta FA,
    3. Dunn JP,
    4. Jabs DA
    . Risk of cataract development among children with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. Ophthalmology 2010;117:1436-41.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Kothari S,
    2. Foster CS,
    3. Pistilli M, et al; Systemic Immunosuppressive Therapy for Eye Diseases Research Group
    . The risk of intraocular pressure elevation in pediatric noninfectious uveitis. Ophthalmology 2015;122:1987-2001.
    OpenUrl
  19. 19.↵
    1. Smith JR,
    2. Matthews JM,
    3. Conrad D, et al; Australian and New Zealand Juvenile Idiopathic Arthritis-Uveitis Working Group
    . Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis. Clin Exp Ophthalmol 2021;49:38-45.
    OpenUrl
  20. 20.↵
    1. Constantin T,
    2. Foeldvari I,
    3. Anton J, et al
    . Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative. Ann Rheum Dis 2018;77:1107-17.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Papadopoulou M,
    2. Zetterberg M,
    3. Oskarsdottir S,
    4. Andersson Grönlund M
    . Assessment of the outcome of ophthalmological screening for uveitis in a cohort of Swedish children with juvenile idiopathic arthritis. Acta Ophthalmol 2017;95:741-7.
    OpenUrl
  22. 22.
    1. Sijssens KM,
    2. Rothova A,
    3. Van De Vijver DA,
    4. Stilma JS,
    5. De Boer JH
    . Risk factors for the development of cataract requiring surgery in uveitis associated with juvenile idiopathic arthritis. Am J Ophthalmol 2007;144:574-9.
    OpenUrlCrossRefPubMed
  23. 23.
    1. Shetty AK,
    2. Zganjar BE,
    3. Ellis GS Jr,
    4. Ludwig IH,
    5. Gedalia A
    . Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis. J Pediatr Ophthalmol Strabismus 1999;36:125-8.
    OpenUrlCrossRefPubMed
  24. 24.
    1. Foeldvari I,
    2. Becker I,
    3. Horneff G
    . Uveitis events during adalimumab, etanercept, and methotrexate therapy in juvenile idiopathic arthritis: data from the Biologics in Pediatric Rheumatology Registry. Arthritis Care Res 2015;67:1529-35.
    OpenUrl
  25. 25.
    1. Heiligenhaus A,
    2. Mingels A,
    3. Heinz C,
    4. Ganser G
    . Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication. Eur J Ophthalmol 2007;17:743-8.
    OpenUrlPubMed
  26. 26.
    1. Wieringa WG,
    2. Armbrust W,
    3. Legger GE,
    4. Los LI
    . Efficacy of high-dose methotrexate in pediatric non-infectious uveitis. Ocul Immunol Inflamm 2019;27:1305-13.
    OpenUrl
  27. 27.↵
    1. Kostik MM,
    2. Gaidar EV,
    3. Hynnes AY, et al
    . Methotrexate treatment may prevent uveitis onset in patients with juvenile idiopathic arthritis: experiences and subgroup analysis in a cohort with frequent methotrexate use. Clin Exp Rheumatol 2016;34:714-8.
    OpenUrl
  28. 28.↵
    1. Jari M,
    2. Shiari R,
    3. Salehpour O,
    4. Rahmani K
    . Epidemiological and advanced therapeutic approaches to treatment of uveitis in pediatric rheumatic diseases: a systematic review and meta-analysis. Orphanet J Rare Dis 2020;15:41.
  29. 29.
    1. Ferrara M,
    2. Eggenschwiler L,
    3. Stephenson A, et al
    . The challenge of pediatric uveitis: tertiary referral center experience in the United States. Ocul Immunol Inflamm 2019;27:410-7.
    OpenUrl
  30. 30.↵
    1. Simonini G,
    2. Paudyal P,
    3. Jones GT,
    4. Cimaz R,
    5. Macfarlane GJ
    . Current evidence of methotrexate efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach. Rheumatology 2013;52:825-31.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Ferrara G,
    2. Mastrangelo G,
    3. Barone P, et al
    . Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting. Pediatr Rheumatol Online J 2018;16:46.
  32. 32.↵
    1. Doycheva D,
    2. Zierhut M,
    3. Blumenstock G, et al
    . Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood. Br J Ophthalmol 2016;100:1071-5.
    OpenUrlAbstract/FREE Full Text
  33. 33.
    1. Doycheva D,
    2. Deuter C,
    3. Stuebiger N,
    4. Biester S,
    5. Zierhut M
    . Mycophenolate mofetil in the treatment of uveitis in children. Br J Ophthalmol 2007;91:180-4.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Chang PY,
    2. Giuliari GP,
    3. Shaikh M,
    4. Thakuria P,
    5. Makhoul D,
    6. Foster CS
    . Mycophenolate mofetil monotherapy in the management of paediatric uveitis. Eye 2011;25:427-35.
    OpenUrlCrossRefPubMed
  35. 35.
    1. Goebel JC,
    2. Roesel M,
    3. Heinz C,
    4. Michels H,
    5. Ganser G,
    6. Heiligenhaus A
    . Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis. Br J Ophthalmol 2011;95:209-13.
    OpenUrlAbstract/FREE Full Text
  36. 36.↵
    1. Tappeiner C,
    2. Roesel M,
    3. Heinz C,
    4. Michels H,
    5. Ganser G,
    6. Heiligenhaus A
    . Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye 2009;23:1192-8.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Jundt JW,
    2. Browne BA,
    3. Fiocco GP,
    4. Steele AD,
    5. Mock D
    . A comparison of low dose methotrexate bioavailability: oral solution, oral tablet, subcutaneous and intramuscular dosing. J Rheumatol 1993;20:1845-9.
    OpenUrlPubMed
  38. 38.↵
    1. Tuková J,
    2. Chládek J,
    3. Nemcová D,
    4. Chládková J,
    5. Dolezalová P
    . Methotrexate bioavailability after oral and subcutaneous administration in children with juvenile idiopathic arthritis. Clin Exp Rheumatol 2009;27:1047-53.
    OpenUrlPubMed
  39. 39.↵
    1. Angeles-Han ST,
    2. Lo MS,
    3. Henderson LA, et al; Juvenile Idiopathic Arthritis Disease-Specific and Uveitis Subcommittee of the Childhood Arthritis Rheumatology and Research Alliance
    . Childhood arthritis and rheumatology research alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis. Arthritis Care Res 2019; 71:482-91.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Lee J,
    2. Koreishi AF,
    3. Zumpf KB,
    4. Minkus CL,
    5. Goldstein DA
    . Success of weekly adalimumab in refractory ocular inflammatory disease. Ophthalmology 2020;127:1431-3.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Correll CK,
    2. Bullock DR,
    3. Cafferty RM,
    4. Vehe RK
    . Safety of weekly adalimumab in the treatment of juvenile idiopathic arthritis and pediatric chronic uveitis. Clin Rheumatol 2018;37:549-53.
    OpenUrl
  42. 42.↵
    1. Kahn P,
    2. Weiss M,
    3. Imundo LF,
    4. Levy DM
    . Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006;113:860-4.e2.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Quartier P
    . Tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. The Lancet Rheumatol 2020;2:e122-e3.
  44. 44.
    1. Birolo C,
    2. Zannin ME,
    3. Arsenyeva S, et al
    . Comparable efficacy of abatacept used as first-line or second-line biological agent for severe juvenile idiopathic arthritis-related uveitis. J Rheumatol 2016;43:2068-73.
    OpenUrlAbstract/FREE Full Text
  45. 45.
    1. Tappeiner C,
    2. Miserocchi E,
    3. Bodaghi B, et al
    . Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2015;42:706-11.
    OpenUrlAbstract/FREE Full Text
  46. 46.
    1. Zulian F,
    2. Balzarin M,
    3. Falcini F, et al
    . Abatacept for severe anti-tumor necrosis factor α refractory juvenile idiopathic arthritis-related uveitis. Arthritis Care Res 2010;62:821-5.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Miserocchi E,
    2. Giuffrè C,
    3. Cornalba M,
    4. Pontikaki I,
    5. Cimaz R
    . JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis. Clin Rheumatol 2020;39:847-51.
    OpenUrlPubMed
  48. 48.↵
    1. Sen HN,
    2. Levy-Clarke G,
    3. Faia LJ, et al
    . High-dose daclizumab for the treatment of juvenile idiopathic arthritis-associated active anterior uveitis. Am J Ophthalmol 2009;148:696-703.e1.
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Miserocchi E,
    2. Modorati G,
    3. Berchicci L,
    4. Pontikaki I,
    5. Meroni P,
    6. Gerloni V
    . Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol 2016;100:782-6.
    OpenUrlAbstract/FREE Full Text
  50. 50.↵
    1. Miserocchi E,
    2. Modorati G,
    3. Pontikaki I,
    4. Meroni PL,
    5. Gerloni V
    . Long-term treatment with golimumab for severe uveitis. Ocul Immunol Inflamm 2014;22:90-5.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Palmou-Fontana N,
    2. Calvo-Río V,
    3. Martín-Varillas JL, et al
    . Golimumab in refractory uveitis associated to juvenile idiopathic arthritis: multicentre study of 7 cases and literature review. Clin Exp Rheumatol 2018;36:652-7.
    OpenUrlPubMed
  52. 52.↵
    1. Skrabl-Baumgartner A,
    2. Erwa W,
    3. Muntean W,
    4. Jahnel J
    . Anti-adalimumab antibodies in juvenile idiopathic arthritis: frequent association with loss of response. Scand J Rheumatol 2015;44:359-62.
    OpenUrl
  53. 53.
    1. Leinonen ST,
    2. Aalto K,
    3. Kotaniemi KM,
    4. Kivelä TT
    . Anti-adalimumab antibodies in juvenile idiopathic arthritis-related uveitis. Clin Exp Rheumatol 2017;35:1043-6.
    OpenUrlPubMed
  54. 54.↵
    1. Cordero-Coma M,
    2. Calleja-Antolín S,
    3. Garzo-García I, et al
    . Adalimumab for treatment of noninfectious uveitis: immunogenicity and clinical relevance of measuring serum drug levels and antidrug antibodies. Ophthalmology 2016;123:2618-25.
    OpenUrlPubMed
  55. 55.↵
    1. Leblanc CM,
    2. Lang B,
    3. Bencivenga A, et al
    . Access to biologic therapies in Canada for children with juvenile idiopathic arthritis. J Rheumatol 2012;39:1875-9.
    OpenUrlAbstract/FREE Full Text
  56. 56.↵
    1. Lee JJY,
    2. Laxer RM,
    3. Feldman BM, et al; Pediatrics Committee of the Canadian Rheumatology Association
    . Variations in pediatric rheumatology workforce and care processes across Canada. J Rheumatol 2021;49:197-204.
    OpenUrl
  57. 57.↵
    1. Bellan L,
    2. Buske L,
    3. Wang S,
    4. Buys YM
    . The landscape of ophthalmologists in Canada: present and future. Can J Ophthalmol 2013;48:160-6.
    OpenUrlCrossRefPubMed

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Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis
Roberta Berard, Hon Yan Ng, Andrea Human, David Piskin, Muhammed Dhalla, Chloe Gottlieb, Michelle Batthish, Gaëlle Chédeville, Christina Forest, Eric Fortin, Jane Gardiner, Kerstin Gerhold, Andre Jastrzebski, Bianca Lang, Paivi M.H. Miettunen, Sabrina Morgenstern, Marie-Paule Morin, Alan Rosenberg, Dax G. Rumsey, Carlos E. Solarte, Nasrin Tehrani, Karen Watanabe Duffy, Jordi Pardo Pardo, Glen S. Hazlewood, Deborah M. Levy
The Journal of Rheumatology Mar 2023, 50 (3) 390-399; DOI: 10.3899/jrheum.220261

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Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis
Roberta Berard, Hon Yan Ng, Andrea Human, David Piskin, Muhammed Dhalla, Chloe Gottlieb, Michelle Batthish, Gaëlle Chédeville, Christina Forest, Eric Fortin, Jane Gardiner, Kerstin Gerhold, Andre Jastrzebski, Bianca Lang, Paivi M.H. Miettunen, Sabrina Morgenstern, Marie-Paule Morin, Alan Rosenberg, Dax G. Rumsey, Carlos E. Solarte, Nasrin Tehrani, Karen Watanabe Duffy, Jordi Pardo Pardo, Glen S. Hazlewood, Deborah M. Levy
The Journal of Rheumatology Mar 2023, 50 (3) 390-399; DOI: 10.3899/jrheum.220261
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Keywords

chronic anterior uveitis
evidence-to-decision framework
GRADE-ADOLOPMENT
GUIDELINES
JUVENILE IDIOPATHIC ARTHRITIS

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Keywords

  • chronic anterior uveitis
  • evidence-to-decision framework
  • GRADE-ADOLOPMENT
  • guidelines
  • juvenile idiopathic arthritis

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