Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

Background: The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. Methods: PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. Results: There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. Conclusion: As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Enhancing Care Partnerships Using a Rheumatology Dashboard: Bringing Together What Matters Most to Both Patients and Clinicians.

OBJECTIVE: Dashboards can support person-centered care by helping people partner with their clinicians to coproduce care based on preferences, shared decision-making, and evidence-based treatments. We engaged caregivers of children with juvenile idiopathic arthritis (JIA), adults with rheumatoid arthritis (RA), and clinicians in a pilot study to assess their experiences and the utility and impact of an electronic previsit questionnaire and point-of-care dashboard to support coproduction of rheumatology care. METHODS: We employed a mixed-methods design to assess users' perceptions of a customized electronic health record rheumatology module at four pediatric rheumatology practices and two adult rheumatology practices. We surveyed a convenience sample of caregivers of children with JIA (n = 113), adults with RA (n = 116), and clinicians (n = 12). We conducted semistructured interviews with 13 caregivers and patients and six care teams. Experiences were evaluated using descriptive statistics and thematic analyses. RESULTS: Caregivers of children with JIA and adults with RA reported the dashboards were useful during discussions (88%) and helped them talk about what mattered most (82%), make health care decisions (83%), and create a treatment plan (77%). Clinicians provided similar feedback. Two-thirds (67%) of caregivers and adults and 55% of clinicians would recommend the dashboard to peers. System usability scores (77.1 ± 15.6) were above average. Dashboards helped users make sense of health information, communicate more effectively, and make decisions. Improvements to the dashboards and workflows could enhance patient self-management and clinician efficiency. CONCLUSION: Visual point-of-care dashboards can support caregivers, patients, and clinicians to coproduce rheumatology care. Findings demonstrate a need to spread and scale for broader benefit and impact.

First-line options for systemic juvenile idiopathic arthritis treatment: an observational study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans.

BACKGROUND: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) to compare treatment initiation strategies for systemic juvenile idiopathic arthritis (sJIA). First-line options for sJIA treatment (FROST) was a prospective observational study to assess CTP outcomes using the CARRA Registry. METHODS: Patients with new-onset sJIA were enrolled if they received initial treatment according to the biologic CTPs (IL-1 or IL-6 inhibitor) or non-biologic CTPs (glucocorticoid (GC) monotherapy or methotrexate). CTPs could be used with or without systemic GC. Primary outcome was achievement of clinical inactive disease (CID) at 9 months without current use of GC. Due to the small numbers of patients in the non-biologic CTPs, no statistical comparisons were made between the CTPs. RESULTS: Seventy-three patients were enrolled: 63 (86%) in the biologic CTPs and 10 (14%) in the non-biologic CTPs. CTP choice appeared to be strongly influenced by physician preference. During the first month of follow-up, oral GC use was observed in 54% of biologic CTP patients and 90% of non-biologic CTPs patients. Five (50%) non-biologic CTP patients subsequently received biologics within 4 months of follow-up. Overall, 30/53 (57%) of patients achieved CID at 9 months without current GC use. CONCLUSION: Nearly all patients received treatment with biologics during the study period, and 46% of biologic CTP patients did not receive oral GC within the first month of treatment. The majority of patients had favorable short-term clinical outcomes. Increased use of biologics and decreased use of GC may lead to improved outcomes in sJIA.

Co-design of an Electronic Dashboard to Support the Coproduction of Care in Pediatric Rheumatic Disease: Human-Centered Design and Usability Testing.

BACKGROUND: The coproduction of care involves patients and families partnering with their clinicians and care teams, with the premise that each brings their own perspective, knowledge, and expertise, as well as their own values, goals, and preferences, to the partnership. Dashboards can display meaningful patient and clinical data to assess how a patient is doing and inform shared decision-making. Increasing communication between patients and care teams is particularly important for children with chronic conditions. Juvenile idiopathic arthritis (JIA), the most common chronic pediatric rheumatic condition, is associated with increased pain, decreased function, and decreased quality of life. OBJECTIVE: The aim of this study is to design a dashboard prototype for use in coproducing care in patients with JIA. We evaluated the use and needs of end users, obtained a consensus on the necessary dashboard data elements, and constructed display prototypes to inform meaningful discussions for coproduction. METHODS: A human-centered design approach involving parents, patients, clinicians, and care team members was used to develop a dashboard to support the coproduction of care in 4 ambulatory pediatric rheumatology clinics. We engaged a multidisciplinary team (n=18) of patients, parents, clinicians, nurses, and staff during an in-person kick-off meeting followed by biweekly meetings. We also leveraged advisory panels. Teams mapped workflows and patient journeys, created personas, and developed dashboard sketches. The final dashboard components were determined via Delphi consensus voting. Low-tech dashboard testing was completed during clinic visits, and visual display prototypes were iterated by using the Plan-Do-Study-Act methodology. Patients and clinicians were surveyed regarding their experiences. RESULTS: Teams achieved consensus on what data mattered most at the point of care to support patients with JIA, families, and clinicians collaborating to make the best possible health care decisions. Notable themes included the right data in the right place at the right time, data in once for multiple purposes, patient and family self-management components, and the opportunity for education and increased transparency. A final set of 11 dashboard data elements was identified, including patient-reported outcomes, clinical data, and medications. Important design considerations featured the incorporation of real-time data, clearly labeled graphs, and vertical orientation to facilitate review and discussion. Prototype paper-testing with 36 patients and families yielded positive feedback, with 89% (8/9) to 100% (9/9) of parents (n=9) and 80% (8/10) to 90% (9/10) of clinicians (n=10) strongly agreeing or agreeing that the dashboard was useful during clinic discussions, helped to talk about what mattered most, and informed health care decision-making. CONCLUSIONS: We developed a dashboard prototype that displays patient-reported and clinical data over time, along with medications that can be used during a clinic visit to support meaningful conversations and shared decision-making among patients with JIA, their families, and their clinicians and care teams.

Translating research into practice-implementation recommendations for pediatric rheumatology; Proceedings of the childhood arthritis and rheumatology research alliance 2020 implementation science retreat.

The translation of research findings into clinical practice is challenging, especially fields like in pediatric rheumatology, where the evidence base is limited, there are few clinical trials, and the conditions are rare and heterogeneous. Implementation science methodologies have been shown to reduce the research- to- practice gap in other clinical settings may have similar utility in pediatric rheumatology. This paper describes the key discussion points from the inaugural Childhood Arthritis and Rheumatology Research Alliance Implementation Science retreat held in February 2020. The aim of this report is to synthesize those findings into an Implementation Science Roadmap for pediatric rheumatology research. This roadmap is based on three foundational principles: fostering curiosity and ensuring discovery, integration of research and quality improvement, and patient-centeredness. We include six key steps anchored in the principles of implementation science. Applying this roadmap will enable researchers to evaluate the full range of research activities, from the initial clinical design and evidence acquisition to the application of those findings in pediatric rheumatology clinics and direct patient care.

Patient Engagement in Pediatric Rheumatology Research.

Patient engagement in pediatric rheumatology research can ensure protocol acceptability, project relevance, facilitate a successful study, and share results with the community. Research partners can collaborate along the entire continuum of research, contributing both lived and professional experience with roles as small as a single point-in-time consultation to as large as multi-year shared leadership. Patient and caregiver partners can be found in the myriad of places-the clinic, in advocacy organizations, on social media, and through networking with existing patient partners. Patient engagement begins with relationship building and requires effective training of both researcher and patient family.

Optimizing the Start Time of Biologics in Polyarticular Juvenile Idiopathic Arthritis: A Comparative Effectiveness Study of Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans.

OBJECTIVE: The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics. METHODS: Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step-up plan (initial nonbiologic disease-modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS-10), and the ACR Pediatric 70 criteria (Pedi 70). RESULTS: Of 400 patients enrolled, 257 (64%) began the step-up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step-up plan, and 24% on the biologic first plan (P = 0.17). Inactive disease according to the clinical JADAS-10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step-up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections). CONCLUSION: Achievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS-10 and ACR Pedi 70, these results require further exploration.

Toward Accelerated Authorization and Access to New Medicines for Juvenile Idiopathic Arthritis.

A meeting was organized to bring together multiple stakeholders involved in the testing and authorization of new medications for juvenile idiopathic arthritis (JIA) to discuss current issues surrounding clinical trials and access to new medications for children and adolescents with JIA. The Childhood Arthritis and Rheumatology Research Alliance invited representatives of regulatory agencies (Food and Drug Administration and European Medicines Agency), and major pharmaceutical companies with JIA-approved products or products in development, patient and parent representatives, representatives of an advocacy organization (Arthritis Foundation), and pediatric rheumatology clinicians/investigators to a 1-day meeting in April 2018. The participants engaged in discussion regarding issues in clinical trials. As the pharmacologic options to treat inflammatory arthritis rapidly expand, registration trial designs to test medications in JIA patients must adapt. Many methodologies successfully used in the recent past are no longer feasible. The pool of patients meeting entry criteria who are willing to participate is shrinking while the number of medications to be tested is growing. Suggested solutions included proposing innovative clinical trial methods to regulatory agencies, as well as open discussions among stakeholders. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critical. Approaches should include open dialog between regulatory agencies, pharmaceutical companies, and other stakeholders to develop and implement novel study designs, including patient and clinician perspectives to define meaningful trial outcomes, and changing existing study plans.

Using registries to identify adverse events in rheumatic diseases.

The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators. In collaboration with the US Food and Drug Administration (FDA), patient and family advocacy groups, biopharmaceutical industry representatives and other stakeholders, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the Duke Clinical Research Institute (DCRI) have developed a novel pharmacosurveillance model (CARRA Consolidated Safety Registry [CoRe]) based on a multicenter longitudinal pediatric rheumatic diseases registry with over 8000 participants. The existing CARRA infrastructure provides access to much larger numbers of subjects than is feasible in single-product registries. Enrollment regardless of medication exposure allows more accurate detection and evaluation of safety signals. Flexibility built into the model allows the addition of specific data elements and safety outcomes, and designation of appropriate disease comparator groups relevant to each product, fulfilling post-marketing requirements and commitments. The proposed model can be applied to other pediatric and adult diseases, potentially transforming the paradigm of pharmacosurveillance in response to the growing public mandate for rigorous post-marketing safety monitoring.