Consensus Approach to a Treat-to-target Strategy in Juvenile Idiopathic Arthritis Care: Report From the 2020 PR-COIN Consensus Conference.

OBJECTIVE: Treat to target (T2T) is a strategy of adjusting treatment until a target is reached. An international task force recommended T2T for juvenile idiopathic arthritis (JIA) treatment. Implementing T2T in a standard and reliable way in clinical practice requires agreement on critical elements of (1) target setting, (2) T2T strategy, (3) identifying barriers to implementation, and (4) patient eligibility. A consensus conference was held among Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) stakeholders to inform a statement of understanding regarding the PR-COIN approach to T2T. METHODS: PR-COIN stakeholders including 16 healthcare providers and 4 parents were invited to form a voting panel. Using the nominal group technique, 2 rounds of voting were held to address the above 4 areas to select the top 10 responses by rank order. RESULTS: Incorporation of patient goals ranked most important when setting a treatment target. Shared decision making (SDM), tracking measurable outcomes, and adjusting treatment to achieve goals were voted as the top elements of a T2T strategy. Workflow considerations, and provider buy-in were identified as key barriers to T2T implementation. Patients with JIA who had poor prognostic factors and were at risk for high disease burden were leading candidates for a T2T approach. CONCLUSION: This consensus conference identified the importance of incorporating patient goals as part of target setting and of the influence of patient stakeholder involvement in drafting treatment recommendations. The network approach to T2T will be modified to address the above findings, including solicitation of patient goals, optimizing SDM, and better workflow integration.

Whole-body MRI Quantification for Assessment of Bone Lesions in Chronic Nonbacterial Osteomyelitis Patients Treated With Pamidronate: A Prevalence, Reproducibility, and Responsiveness Study.

OBJECTIVE: The purpose of this study was (1) to assess the interreader reliability in detecting and scoring the inflammatory bone lesions in pediatric patients with chronic nonbacterial osteomyelitis (CNO) by using whole-body magnetic resonance imaging (WB-MRI), and (2) to evaluate the responsiveness of the MRI-detected CNO lesions to pamidronate therapy. METHODS: Eighty-eight WB-MRI examinations were independently reviewed and scored by 2 radiologists blinded to clinical details in 32 retrospectively enrolled pediatric patients with CNO. Inflammatory bone lesions, soft tissue abnormality, and bony structural changes were scored before and after pamidronate therapy. Lesion responsiveness was calculated by using standardized response mean and interreader reliability was assessed by k statistics. RESULTS: There was good to excellent interreader agreement for the detection and quantification of bone lesions. After the first cycle of pamidronate in all 32 patients, 96 of the 279 lesions (34%; after excluding 108 lesions of hand and feet) resolved, whereas in a subset of 11 patients with 2 or more cycles, 76% of lesions resolved after the second cycle. Twenty-one (7.5%) lesions worsened and 46 (16.4%) new lesions developed after 1 cycle in all 32 patients. In these 11 patients, the number of worsened lesions reduced to 2 (2%) and new lesions to 14 (14.9%) after the second cycle as detected on MRI. Vertebral lesions had the highest response to treatment. CONCLUSION: WB-MRI is a reliable tool for objective quantification and assessment of response to treatment of pediatric CNO bone lesions and could be used to monitor disease activity for clinical and research purposes.

The use of biologic response modifiers in polyarticular-course juvenile idiopathic arthritis: a systematic review.

OBJECTIVE: To systematically review the clinical efficacy and safety evidence of biologic drugs used to treat the polyarticular category of juvenile idiopathic arthritis (JIA). METHODS: The literature was searched between 2000 and September 2012 for randomized controlled trials (RCTs), non-randomized comparative studies, and non-comparative observational cohort studies. The drugs evaluated included etanercept, infliximab, adalimumab, abatacept, anakinra, and ritixumab. Eligible studies included 20 or more patients with JIA, the majority of whom had polyarticular course disease. Outcomes of interest were disease improvement defined by the American College of Rheumatology criteria for Pediatrics, disease flares, rates of inactive disease, remissions, discontinuations, and adverse events (severe and non-severe). RESULTS: Thirty-seven studies were included, the majority focused on etanercept. Seven RCTs were identified, including one each for etanercept, infliximab, adalimumab, abatacept, and anakinra, and one each looking at etanercept or infliximab as first-line therapies. There was strong evidence to support the efficacy and safety of biologics over the short-term, but a lack of long-term data for treatments other than etanercept. Several high-quality patient registries confirmed the efficacy and safety of etanercept over the long-term. CONCLUSIONS: Current evidence shows that a short-term improvement in treatment response is achieved when patients with polyarticular JIA with an inadequate response to conventional treatment are treated with biologics. Long-term effectiveness data, however, are sparse leaving many questions regarding switches between biologics, handling patients that achieve disease remission, and long-term safety. Study designs other than RCTs may be important in understanding the role of biologics in JIA over the long-term.

Cost-effectiveness of biologics in polyarticular-course juvenile idiopathic arthritis patients unresponsive to disease-modifying antirheumatic drugs.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease and can have long-term effects leading to disability in adulthood. Biologics are a new class of drugs increasingly used to treat JIA. The primary study objective was to determine the incremental costs of biologics per additional responder compared to conventional treatment (methotrexate). METHODS: A separate decision model was created for etanercept, infliximab, adalimumab, and abatacept. The study population consisted of polyarticular-course JIA patients with a prior inadequate response or intolerance to disease-modifying antirheumatic drugs (DMARDs). The effectiveness measure was the proportion of patients who had a treatment response at 1 year according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) improvement criteria. Direct and indirect costs were calculated in 2008 Canadian dollars. Incremental cost-effectiveness ratios and 95% confidence intervals (95% CIs) were calculated for each biologic agent using probabilistic sensitivity analyses. RESULTS: The additional costs per additional ACR Pedi 30 responder at 1 year were $26,061 (95% CI $17,070, $41,834), $46,711 (95% CI $30,042, $75,787), $16,204 (95% CI $11,393, $22,608), and $31,209 (95% CI $16,659, $66,220) for etanercept, adalimumab, abatacept, and infliximab, respectively. CONCLUSION: Biologics are more effective than methotrexate in achieving a short-term response in JIA patients with prior inadequate responses to DMARDs; however, this comes at a high annual cost. Adequate long-term data with respect to both safety and effectiveness are not currently available, nor are utility estimates. Such data will be important to estimate value for money for treating JIA with biologic drugs over the long term.