Objectives Pompe disease is a progressive neuromuscular disorder due to acid alpha glucosidase (GAA) deficiency. Cross-reacting immunologic material (CRIM)-negative infants with null GAA mutations have the most severe phenotype and develop anti-GAA antibodies following exposure to enzyme replacement therapy (ERT). Antibodies influence bio-distribution, attenuate the beneficial effects of ERT, and are believed to influence infusion-associated reactions (IARs), which occur in nearly all early-onset patients. We evaluated the potential that B-cell depletion prior to ERT initiation would block GAA antibody responses and improve clinical outcome. Study Design Six Pompe subjects (four CRIM-negative) between 2–8 months of age received rituximab and sirolimus or myophenolate prior to ERT. Four subjects continued to receive sirolimus, every 12-week rituximab and monthly intravenous immunoglobulin for the duration of ERT. Sirolimus trough levels, IgG levels, CD3, CD4, CD8, CD19, CD20, NTproBNP, CK, CK-MB, CRP, platelet, alkaline phosphatase, AST, ALT were measured regularly. Results Immunomodulation achieved B-cell depletion without adverse effects. After 17–36 months of rituximab, sirolimus and ERT, all subjects lacked antibodies against GAA, four continued to gain motor milestones, yet two progressed to require invasive ventilation. Absence of infusion associated reactions allowed accelerated infusion rates. No IARs were observed at standard or accelerated infusion rates. Conclusions B-cell depletion and T-cell immunomodulation in infants naïve to ERT was accomplished safely, eliminated immune responses against GAA, thereby optimizing clinical outcome, however this approach did not necessarily influence sustained independent ventilation. Importantly, study outcomes support the concept of initiating immunomodulation prior to beginning ERT since the study regimen allowed for prompt initiation of treatment.
BackgroundThe prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960’s with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011–2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA).MethodsThe JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011–2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013–2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.ResultsOne hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups.ConclusionsOur CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future.Significance and InnovationsThis is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years.This experience with biologic thera...
BackgroundSystemic juvenile idiopathic arthritis (SJIA)/Still's disease is a rare form of chronic arthritis in pediatrics. The patient perspective of living with the disease is not well understood, particularly among adolescent age patients.ObjectivesThe objective was to understand the adolescent SJIA experience as shown by their own social media posts.MethodsEnglish posts from SJIA patients were reviewed on public social media sites.Results71 posts with a date range of 2009–2015 on 15 sites were reviewed in Nov 2015. 24 unique authors were identified: 17 SJIA patients (40 posts) and 7 mothers of SJIA patients (12 posts). Patients were aged 13–20 years. Several patients posted about similar diagnostic experiences marked by 5 stages: (1) misunderstood with their pain and fatigue being overlooked until a crisis occurs, (2) dismissed as “fakers”, where their initial misdiagnosis is often “growing pains” or “fake pains”, (3) misdiagnosis, often as cancer, when the symptoms acutely worsen (4) testing stage that leads to an SJIA diagnosis, and (5) focus on the difficulties of dealing with a chronic invisible disease where they feel ashamed of their arthritis and distressed at being different from their peers. Many adolescent patients, looking back at the onset of the disease when they were children, describe themselves as a “sleeping child” rather than the typical active, playing child. Patients describe trying to hide their illness from friends, but express their concerns more openly online. Patients also describe anger directed at SJIA which is described as a powerful external enemy attacking their body, using terms like “bulldozer,” “dragon”, and “monster'.' Many posters used superhero language or imagery in their social media posts to help them “fight” the disease and their struggle. Mothers of SJIA patients also used warrior-child imagery and language in their posts. Some SJIA patients also posted about the risk of death, or shared stories about other SJIA patients who died which is a distinct difference from non-SJIA patients. Many patients also have adopted the term “spoonie” to describe themselves as living with a chronic disease, a term that originated in the autoimmune community to refer to how people with chronic conditions manage their energy throughout the day. Only the older teenagers used the term Still's.ConclusionsAdolescent SJIA patients posted openly about the difficulties of their disease causing them to be different from their healthy friends, whereas in the real world they tried to minimize or hide the effects of their disease. They frequently used superhero words and images in posts in describing their fight for health. Physicians can use these insights when counseling adolescent SJIA patients to provide a narrative that meshes with the patients' worldview and perhaps, by speaking a similar language, could increase treatment adherence.Disclosure of InterestR. Modica: None declared, K. Lomax Employee of: Novartis Pharmaceuticals Corp, P. Batzel: None declared, A. Cassanas: None declared, M. Elder: ...
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