Treatment Withdrawal Following Remission in Juvenile Idiopathic Arthritis: A Systematic Review of the Literature

Halyabar, Olha; Mehta, Jay; Ringold, Sarah; Rumsey, Dax G.; Horton, Daniel B.

doi:10.1007/s40272-019-00362-6

Cited by 43 publications

(37 citation statements)

References 84 publications

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“…The task force also discussed plans for de‐escalation of therapy for patients who remain in clinical remission while on medications. While the task force agreed that patients should not be kept on prolonged immunomodulatory therapy unnecessarily, shared decision‐making among patients, families, and providers was recommended to discuss potential consequences of withdrawing medications, including risks of disease flare, followed by a need for increased in‐person visits, laboratory monitoring, and, potentially, the need for escalation of therapy (including the use of glucocorticoids) (40–42).…”

Section: Resultsmentioning

confidence: 99%

American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID‐19 Pandemic: Version 1

Wahezi

Rubinstein

et al. 2020

Arthritis & Rheumatology

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Objective To provide clinical guidance to rheumatology providers who treat children with pediatric rheumatic disease (PRD) in the context of the coronavirus disease 2019 (COVID‐19) pandemic. Methods The task force, consisting of 7 pediatric rheumatologists, 2 pediatric infectious disease physicians, 1 adult rheumatologist, and 1 pediatric nurse practitioner, was convened on May 21, 2020. Clinical questions and subsequent guidance statements were drafted based on a review of the queries posed by the patients as well as the families and healthcare providers of children with PRD. An evidence report was generated and disseminated to task force members to assist with 3 rounds of asynchronous, anonymous voting by email using a modified Delphi approach. Voting was completed using a 9‐point numeric scoring system with predefined levels of agreement (categorized as disagreement, uncertainty, or agreement, with median scores of 1–3, 4–6, and 7–9, respectively) and consensus (categorized as low, moderate, or high). To be approved as a guidance statement, median vote ratings were required to fall into the highest tertile for agreement, with either moderate or high levels of consensus. Results The task force drafted 33 guidance statements, which were voted upon during the second and third rounds of voting. Of these 33 statements, all received median vote ratings within the highest tertile of agreement and were associated with either moderate consensus (n = 6) or high consensus (n = 27). Statements with similar recommendations were combined, resulting in 27 final guidance statements. Conclusion These guidance statements have been generated based on review of the available literature, indicating that children with PRD do not appear to be at increased risk for susceptibility to SARS–CoV‐2 infection. This guidance is presented as a “living document,” recognizing that the literature on COVID‐19 is rapidly evolving, with future updates anticipated.

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Section: Resultsmentioning

confidence: 99%

American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID‐19 Pandemic: Version 1

Wahezi

Rubinstein

et al. 2020

Arthritis & Rheumatology

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“…However, stopping treatment also poses risks of subsequent disease flares, which may or may not respond to the same regimens that once kept the disease well‐controlled. Decisions about when to stop effective medicines are particularly challenging given the lack of high‐quality evidence on individual risks of flare after treatment withdrawal, reliable strategies for withdrawing treatment, and the likelihood of regaining disease control (i.e., recapture) after treatment reinitiation (20). Clinicians may have different priorities (e.g., maintaining remission) from patients and families (e.g., achieving a sense of normalcy, eliminating ongoing side effects or costs, or avoiding long‐term treatment‐related harms).…”

Section: Discussionmentioning

confidence: 99%

“…Biomarkers for guiding decisions on treatment withdrawal have been tested (17) but not sufficiently validated for routine clinical use (18). Choices about stopping treatment are further complicated by insufficient data on effective withdrawal strategies (19,20).…”

Section: Introductionmentioning

confidence: 99%

Making Decisions About Stopping Medicines for Well‐Controlled Juvenile Idiopathic Arthritis: A Mixed‐Methods Study of Patients and Caregivers

Horton

Salas

Wec

et al. 2021

Arthritis Care & Research

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Objective Improved treatments for juvenile idiopathic arthritis (JIA) have increased remission rates. We conducted this study to investigate how patients and caregivers make decisions about stopping medications when JIA is inactive. Methods We performed a mixed‐methods study of caregivers and patients affected by JIA, recruited through social media and flyers, and selected by purposive sampling. Participants discussed their experiences with JIA, medications, and decision‐making through recorded telephone interviews. Of 44 interviewees, 20 were patients (50% ages <18 years), and 24 were caregivers (50% caring for children ages ≤10 years). We evaluated characteristics associated with high levels of reported concerns about JIA or medicines using Fisher’s exact testing. Results Decisions about stopping medicines were informed by competing risks between disease activity and treatment. Participants who expressed more concerns about JIA were more likely to report disease‐related complications (P = 0.002) and more motivated to continue treatment. However, participants expressing more concern about medicines were more likely to report treatment‐related complications (P = 0.04) and felt more compelled to stop treatment. Additionally, participants considered how JIA or treatments facilitated or interfered with their sense of normalcy and safety, expressed feelings of guilt and regret about previous or potential adverse events, and reflected on uncertainty and unpredictability of future harms. Decision‐making was also informed by trust in rheumatologists and other information sources (e.g., family and online support groups). Conclusion When deciding whether to stop medicines whenever JIA is inactive, patients and caregivers weigh competing risks between disease activity and treatment. Based on our results, we suggest specific approaches for clinicians to perform shared decision‐making regarding stopping medicines for JIA.

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“…The ultimate goal for patients with JIA, as with other chronic diseases, is to achieve remission off medications, with obvious benefits for the patient as well as society, through improved productivity and reduced costs of health care. A systematic review of treatment withdrawal in JIA patients in remission described that the frequency of flares ranged from 30 to 100% in different studies ( Halyabar et al, 2019 ). Data from a Canadian inception cohort showed that the probability of flare (defined as no longer fulfilling the criteria of inactive disease) within 12 months of attaining inactive disease was 42.5% and that of requiring treatment intensification was 26.6% ( Guzman et al, 2016 ).…”

Section: Various Predictor Biomarkers For Successful Withdrawal Of Bimentioning

confidence: 99%

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis

et al. 2021

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Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA.Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA.Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA.Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications.Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.

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Treatment Withdrawal Following Remission in Juvenile Idiopathic Arthritis: A Systematic Review of the Literature

Cited by 43 publications

References 84 publications

American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID‐19 Pandemic: Version 1

American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID‐19 Pandemic: Version 1

Making Decisions About Stopping Medicines for Well‐Controlled Juvenile Idiopathic Arthritis: A Mixed‐Methods Study of Patients and Caregivers

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis

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