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1.
Arthritis Rheumatol ; 72(2): 326-334, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31513353

RESUMO

OBJECTIVE: To assess the benefit of the recombinant human interleukin-1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) associated with rheumatic and nonrheumatic conditions. METHODS: A retrospective chart review of all anakinra-treated patients with secondary HLH/MAS was performed at Children's of Alabama from January 2008 through December 2016. Demographic, clinical, laboratory, and genetic characteristics, outcomes data, and information on concurrent treatments were collected from the records and analyzed using appropriate univariate statistical approaches to assess changes following treatment and associations between patient variables and outcomes. RESULTS: Forty-four patients with secondary HLH/MAS being treated with anakinra were identified in the electronic medical records. The median duration of hospitalization was 15 days. The mean pretreatment serum ferritin level was 33,316 ng/ml and dropped to 14,435 ng/ml (57% decrease) within 15 days of the start of anakinra treatment. The overall mortality rate in the cohort was 27%. Earlier initiation of anakinra (within 5 days of hospitalization) was associated with reduced mortality (P = 0.046), whereas thrombocytopenia (platelet count <100,000/µl) and STXBP2 mutations were both associated with increased mortality (P = 0.008 and P = 0.012, respectively). In considering patients according to their underlying diagnosis, those with systemic juvenile idiopathic arthritis (JIA) had the lowest mortality rate, with no deaths among the 13 systemic JIA patients included in the study (P = 0.006). In contrast, those with an underlying hematologic malignancy had the highest mortality rate, at 100% (n = 3). CONCLUSION: These findings suggest that anakinra appears to be effective in treating pediatric patients with non-malignancy-associated secondary HLH/MAS, especially when it is given early in the disease course and when administered to patients who have an underlying rheumatic disease.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31880862

RESUMO

OBJECTIVE: Improved treatments for juvenile idiopathic arthritis (JIA) have increased remission rates. We investigated how patients and caregivers make decisions about stopping medications for well-controlled JIA. 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% <18 years) and 24 were caregivers (50% of children ≤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 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, online support groups. CONCLUSION: When deciding whether to stop medicines for well-controlled JIA, patients and caregivers weigh competing risks between disease and treatment. Based on our results, we suggest specific approaches for clinicians to perform shared decision-making around stopping medicines for JIA.

3.
Pediatr Rheumatol Online J ; 17(1): 77, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775898

RESUMO

BACKGROUND: Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD. METHODS: A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was performed from 1990 through 2017. Relevance screening was performed by two independent reviewers. Inclusion criteria included English-only, original clinical data. Eight studies met the inclusion criteria. Fever resolution, coronary lesions, and adverse event outcomes were extracted and pooled for analysis. RESULTS: Of the 388 patients included from the 8 studies analyzed, a majority received a second IVIg dose (n = 263, 68%). Fever resolution was comparable between IVIg (72%) and IVMP (73%). IFX (88%) significantly increased fever resolution by approximately 20% compared to IVIg re-dose (RR 1.2; [95% CI: 1.1-1.4]; p = 0.03) and IVMP (RR 1.2; [95% CI: 1.0-1.5]; p = 0.04). Clinical significance of differences in coronary outcomes remains unclear. CONCLUSIONS: This combined analysis was limited due to variability in design and data reporting methods between the studies and risk of bias. In the absence of a clinical trial, IFX monotherapy as second-line treatment should be considered in patients who fail to respond to initial IVIg. This conclusion is based on a systematic review of the literature with pooled outcome data analysis suggesting IFX is more effective in fever resolution compared to a second IVIg dose and IVMP.

4.
ACR Open Rheumatol ; 1(6): 345-349, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31777812

RESUMO

Objective: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA). Early diagnosis is critical. Classification criteria for MAS in sJIA perform less well in the setting of cytokine-directed therapies. The goal herein was to explore a simple ratio of serum ferritin to the erythrocyte sedimentation rate (ESR) for diagnosis of MAS in the setting of sJIA, and to assess ferritin alone as a screening tool for identifying MAS of multiple etiologies. Methods: Data from a large international cohort of sJIA patients with and without MAS, and from hospitalized patients with systemic infection (SI), were assessed for the ferritin:ESR ratio and ferritin alone to identify MAS among sJIA patients. Moreover, data from a smaller cohort of MAS patients associated with multiple etiologies and febrile hospitalized controls were explored. For both cohorts and controls, receiver operating characteristic curves (ROCs) for the ferritin:ESR ratio and ferritin alone were constructed, and areas under the curves (AUCs) were calculated. The Youden index was used to determine the optimal ferritin:ESR ratio and ferritin alone cut points for diagnosis. Results: A ferritin:ESR ratio of 21.5 was 82% sensitive and 78% specific for diagnosing sJIA-MAS versus active sJIA without MAS. Ferritin alone with a set sensitivity of 95% (screening tool) had an 89.3% specificity of identifying all-cause MAS versus febrile hospitalized children. Conclusion: The ferritin:ESR ratio is a practical tool for diagnosing MAS among sJIA patients, and serum ferritin alone is a remarkable screening tool for identifying MAS among febrile hospitalized children.

5.
Arthritis Rheumatol ; 71(12): 1976-1984, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31313532

RESUMO

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.

6.
Arthritis Rheumatol ; 71(6): 864-877, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31021511

RESUMO

OBJECTIVE: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). METHODS: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. RESULTS: Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. CONCLUSION: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/terapia , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/uso terapêutico , Administração Oftálmica , Artrite Juvenil/complicações , Humanos , Infliximab/uso terapêutico , Programas de Rastreamento , Uveíte/diagnóstico , Uveíte/etiologia
7.
Arthritis Care Res (Hoboken) ; 71(6): 717-734, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31021516

RESUMO

OBJECTIVE: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. METHODS: The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. RESULTS: Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. CONCLUSION: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

8.
Arthritis Rheumatol ; 71(6): 846-863, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31021537

RESUMO

OBJECTIVE: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. METHODS: The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. RESULTS: Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. CONCLUSION: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/terapia , Entesopatia/terapia , Glucocorticoides/uso terapêutico , Sacroileíte/terapia , /uso terapêutico , Artrite/terapia , Humanos , Injeções Intra-Articulares , Terapia Ocupacional , Modalidades de Fisioterapia
9.
Arthritis Care Res (Hoboken) ; 71(6): 703-716, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31021540

RESUMO

OBJECTIVE: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). METHODS: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. RESULTS: Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. CONCLUSION: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

10.
J Oral Maxillofac Surg ; 77(6): 1180-1186, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30776331

RESUMO

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that commonly affects the lungs, lymph nodes, and skin. The disease often presents in patients between the third and sixth decade and its pathology is defined by the presence of noncaseating granulomas within organs throughout the body. Oral and neurologic involvement of sarcoid is extremely rare and occurs in approximately 1% and 5% of patients with the disease, respectively. A case of sarcoidosis involving the gingiva and submandibular lymph nodes is described in a 14-year-old girl. Further neural involvement of the disease was recognized after initial biopsy examinations and systemic evaluation. This presentation is especially rare given the patient's lack of symptoms, age at diagnosis, and initial oral manifestations.

12.
Arthritis Care Res (Hoboken) ; 71(4): 482-491, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29806733

RESUMO

OBJECTIVE: Systemic immunosuppressive treatment of pediatric chronic anterior uveitis (CAU), both juvenile idiopathic arthritis-associated and idiopathic anterior uveitis, varies, making it difficult to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments using comparative effectiveness analysis techniques. METHODS: A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup that performed a literature review on pharmacologic treatments, held teleconferences, and developed a case-based survey administered to the CARRA membership to delineate treatment practices. We held 3 face-to-face consensus meetings using nominal group technique to develop CTPs. RESULTS: The survey identified areas of treatment practice variability. We developed 2 CTPs for the treatment of CAU, case definitions, and monitoring parameters. The first CTP is directed at children who are naive to steroid-sparing medication, and the second at children initiating biologic therapy, with options for methotrexate, adalimumab, and infliximab. We defined a core data set and outcome measures, with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted to accept the CTPs with a >95% approval (n = 233). CONCLUSION: Using consensus methodology, 2 standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/complicações , Metotrexato/uso terapêutico , Uveíte Anterior/tratamento farmacológico , Criança , Protocolos Clínicos , Técnica Delfos , Humanos , Uveíte Anterior/etiologia
13.
Arthritis Rheumatol ; 71(3): 451-459, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225949

RESUMO

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Calgranulina A/sangue , Calgranulina B/sangue , Proteína S100A12/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento
14.
Pediatr Rheumatol Online J ; 16(1): 71, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428889

RESUMO

BACKGROUND: Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is characterized by non-thrombocytopenic purpura, abdominal pain, arthritis, and glomerulonephritis. Typically, HSP is self-limited requiring only supportive care, but more severe cases may require corticosteroid (CS) treatment. Rarely, a subset of these patients has persistent rash, arthritis, abdominal involvement, or renal disease despite treatment with CS, or has disease recurrence on CS tapering. Refractory HSP has been effectively treated with a variety of CS sparing therapies. For life-threatening refractory HSP, the B cell depleting agent, rituximab (RTX), has been reported as beneficial for children with substantial renal or central nervous system involvement. However, RTX use for children with less severe HSP, but chronic CS dependent disease refractory to CS sparing immunomodulatory agents, has been less well explored. Herein, we describe 8 children treated with RTX for chronic refractory HSP and report a reduction in recurrent hospitalizations and eventual CS discontinuation. METHODS: This is a retrospective analysis of eight children who were treated with RTX for chronic CS dependent HSP during the years 2006-2014 at a single institution. A chart review of the electronic medical record was performed to determine the presenting symptoms, the type and duration of treatment received, and the number of hospitalizations prior to and after RTX. The number of hospitalizations and oral corticosteroid burden were analyzed using the Wilcoxon signed rank test. RESULTS: Prior to receiving RTX, seven patients had at least one hospitalization for HSP (median 1.5, range 0-3). Following RTX, only two patients were hospitalized, each a single time for recurrent abdominal pain. The median oral CS burden was 0.345 mg/kg/day before RTX and 0 mg/kg/day at 6 months (p = 0.078), 1 year (p = 0.0625), and 2 years (p = 0.03) following RTX infusion. Seven out of eight children met remission criteria, defined as no active rash, arthritis, nephritis (hematuria and proteinuria), or gastrointestinal distress following RTX. No serious adverse events were noted. CONCLUSION: Overall, RTX effectively reduced the number of hospital admissions and oral CS burden. RTX also helped most all children achieve clinical remission. RTX appears to be an effective and safe alternative for chronic CS dependent and immunomodulatory refractory childhood HSP.


Assuntos
Glucocorticoides/administração & dosagem , Fatores Imunológicos/uso terapêutico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Retrospectivos
15.
JAMA Intern Med ; 178(9): 1224-1229, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30073275

RESUMO

Importance: Statin medications are widely prescribed for cardiovascular risk reduction. Myalgia and rhabdomyolysis are well-recognized adverse effects of statins, and they resolve with the cessation of statin therapy. Idiopathic inflammatory myositis (IIM) is a heterogeneous group of autoimmune myopathies that may also be associated with statin use. Recently, statin-associated autoimmune myopathy has been recognized as a distinct entity with the presence of specific autoantibodies against hydroxymethylglutaryl-coenzyme A reductase, which results in a necrotizing myositis that does not resolve with cessation of statin therapy and requires treatment with immunosuppressive agents. Objective: To examine the association between histologically confirmed IIM and current exposure to statin medications. Design, Setting, and Participants: Population-based case-control study using the South Australian Myositis Database of all histologically confirmed cases of IIM diagnosed between 1990 and 2014 in patients 40 years or older (n = 221) and population-based controls from the North West Adelaide Health Study (n = 662), matched by age and sex in a 3:1 ratio of controls to cases. Data analysis using conditional logistic regression was performed from June 1, 2016, to July 14, 2017. Exposures: Current statin medication use. Main Outcomes and Measures: Unadjusted and adjusted (for diabetes and cardiovascular disease) odds ratios and 95% CIs for likelihood of inflammatory myositis. Results: A total of 221 IIM cases met the inclusion criteria with a mean (SD) age of 62.2 (10.8) years, and 132 (59.7%) were female. Statin exposure at the time of IIM diagnosis was 68 of 221 patients (30.8%) and 142 of 662 matched controls (21.5%) (P = .005). There was an almost 2-fold increased likelihood of statin exposure in patients with IIM compared with controls (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60; P = .001). Similar results were observed when patients with necrotizing myositis were excluded from the analysis (adjusted odds ratio, 1.92; 95% CI, 1.29-2.86; P = .001). Conclusions and Relevance: In this large population-based study, statin exposure was significantly associated with histologically confirmed IIM. Given the increased use of statins worldwide and the severity of IIM, increased awareness and recognition of this potentially rare adverse effect of statin exposure is needed.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Músculo Esquelético/patologia , Miosite/induzido quimicamente , Vigilância da População , Sistema de Registros , Adulto , Biópsia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Miosite/epidemiologia , Miosite/patologia , Estudos Retrospectivos , Fatores de Risco , Austrália do Sul/epidemiologia
16.
Pediatr Clin North Am ; 65(4): 657-674, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30031492

RESUMO

Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous diseases further divided into various categories based on shared clinical presentation, laboratory markers, and disease prognosis. Extra-articular complications include uveitis and growth abnormalities. Disease course and prognosis vary with respect to each JIA category and subsequently guide respective treatment. Over the past few decades, considerable treatment advances have significantly reduced the morbidity associated with childhood arthritis. Nevertheless, the treatments are not curative; many children continue to have active disease into adulthood. Emphasis is placed on the initiation of early aggressive therapy in hopes of delaying disease progression and inducing remission.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Juvenil/classificação , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Criança , Humanos
17.
J Rheumatol ; 45(9): 1301-1307, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29764966

RESUMO

OBJECTIVE: Intraarticular corticosteroid (IAC) injections are often used to treat temporomandibular joint (TMJ) arthritis associated with juvenile idiopathic arthritis (JIA). One potential complication of IA therapy is heterotopic bone formation (HBF). The purpose of our study was to evaluate risk factors for HBF development in children with JIA who received IA therapy for TMJ arthritis. METHODS: This was a retrospective study of children with JIA who had received ≥ 1 IAC injection into the TMJ. Survival regression analysis was performed to identify risk factors for the development of HBF. RESULTS: There were 238 children included, of whom 33 (14%) developed HBF. No cases of HBF were diagnosed prior to the initial injection. Univariate analysis revealed that the risk factors for development of HBF were the total number of injections received into the TMJ and age at diagnosis of JIA, while the length of time from diagnosis of JIA to the first injection was inversely associated with the risk of HBF formation. The total number of injections was no longer significant following adjusted survival models. Children with HBF had increased physical examination evidence of acute or chronic changes, namely decreased maximal incisal opening and increased likelihood of jaw deviation. CONCLUSION: HBF within the TMJ is relatively common in patients with JIA receiving IAC injections for TMJ arthritis. Future prospective studies are required to delineate the risks posed by the injections themselves as opposed to the underlying disease activity, as well as to evaluate alternative forms of local therapy to the TMJ.


Assuntos
Corticosteroides/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Ossificação Heterotópica/induzido quimicamente , Articulação Temporomandibular/patologia , Adolescente , Corticosteroides/uso terapêutico , Artrite Juvenil/patologia , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intra-Articulares , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos , Fatores de Risco
18.
Arthritis Rheumatol ; 70(9): 1508-1518, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29604189

RESUMO

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/patologia , Quimioterapia de Indução/estatística & dados numéricos , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Tábuas de Vida , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Clin Trials ; 15(3): 268-277, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29542334

RESUMO

BACKGROUND: Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely. PURPOSE: To describe a pragmatic, observational comparative effectiveness study that takes advantage of diversity in the management of a rare disease: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST), comparing non-biologic and biologic consensus treatment plans for new-onset systemic juvenile idiopathic arthritis within the 60-center Childhood Arthritis and Rheumatology Research Alliance Registry (CARRA). METHODS: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) is a multicenter, prospective, non-randomized study that compares four Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis: (1) glucocorticoids alone, (2) methotrexate, (3) interleukin-1 blockade, and (4) interleukin-6 blockade. Patients consenting to participation in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry are started on one of four Consensus Treatment Plans at the discretion of the treating physician. The outcome of primary interest is clinically inactive disease off glucocorticoids at 9 months, comparing non-biologic (Consensus Treatment Plans 1 + 2) versus biologic (Consensus Treatment Plans 3 + 4) strategies. Bayesian analytic methods will be employed to evaluate response rates, using propensity scoring to balance treatment groups for potential confounding. With 200 patients in a 2:1 ratio of biologic to non-biologic, there is a >90% probability of finding biologic consensus treatment plans more effective if the rate of clinically inactive disease is 30% higher than for non-biologic therapy. Additional outcomes include Patient-Reported Outcomes Measurement Information System measures and other parent-/patient-reported outcomes reported in real time using smartphone technology. Routine operation of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry will allow assessment of outcomes over at least 10 years. RESULTS: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) began enrollment in November 2016. LIMITATIONS: The observational design may not provide balance in measured and unmeasured confounders. Use of consensus treatment plan (CTP) strategies at frequencies more unbalanced than predicted could reduce the chance of finding differences in efficacy. CONCLUSION: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) will provide the first prospective comparison of Childhood Arthritis and Rheumatology Research Alliance's (CARRA's) consensus-derived non-biologic versus biologic management strategies in systemic juvenile idiopathic arthritis, performed in a real-world setting wherein each patient receives standard-of-care treatment selected by the treating physician. Outcomes include clinician- and patient-/family-reported outcomes, empowering both physician and patient decision making in new-onset systemic juvenile idiopathic arthritis.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Terapia Biológica/métodos , Glucocorticoides/administração & dosagem , Metotrexato/administração & dosagem , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos , Teorema de Bayes , Terapia Biológica/efeitos adversos , Criança , Consenso , Glucocorticoides/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Projetos Piloto , Sistema de Registros
20.
Ann Rheum Dis ; 77(7): 1012-1016, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29440001

RESUMO

OBJECTIVE: To determine whether tumour necrosis factor inhibitor (TNFi) use is associated with an increased rate of incident malignancy compared with no TNFi use in the treatment of juvenile idiopathic arthritis (JIA), paediatric inflammatory bowel disease (pIBD) and paediatric plaque psoriasis (pPsO). METHODS: We performed a retrospective cohort study of administrative claims data from the USA from 2000 to 2014. Exposure to TNFi was considered permanent from the first observed exposure onward. The malignancy outcome was defined by diagnosis codes with evidence of cancer treatment. We calculated standardised incidence ratios (SIRs) comparing the observed number of malignancies to the expected numbers according to cancer surveillance data. We used multivariable Cox proportional hazards models to estimate adjusted HRs (aHRs) for incident malignancy. RESULTS: We identified 15 598 children with TNFi use and 73 839 children with no TNFi use (30 703 and 121 801 person-years of follow-up, respectively). We identified 15 malignancies among children with TNFi use (SIR 2.9 (1.6 to 4.9)) and 42 malignancies among children without TNFi use (SIR 2.1 (1.5 to 2.9)). The aHR was 1.58 (0.88 to 2.85) for TNFi use versus no TNFi use. In pIBD, TNFi use with thiopurine use was associated with a higher SIR (6.0 (1.2 to 17.5)) compared with TNFi use without thiopurine use (2.5 (0.7 to 6.4)). CONCLUSION: Children diagnosed with JIA, pIBD and pPsO had an increased rate of malignancy compared with the general population, but treatment with TNFi did not appear to significantly further increase the risk compared with no TNFi use. More data are needed about the long-term risks of TNFi use.


Assuntos
Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Distribuição por Idade , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Análise Multivariada , Neoplasias/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Fator de Necrose Tumoral alfa/administração & dosagem , Estados Unidos
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