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Magnetic resonance imaging (MRI) of the musculoskeletal system is an examination increasingly performed for suspected juvenile idiopathic arthritis, chronic nonbacterial osteomyelitis and juvenile idiopathic inflammatory myopathies, as well as other rheumatic diseases of developmental age. T1-, T2- and PD-weighted with or without fat suppression or short tau inversion recovery/turbo inversion recovery magnitude (STIR/TIRM) sequences and post-contrast sequences are evaluated to diagnose pathological changes in the synovial membrane, subchondral bone marrow and surrounding soft tissues. Magnetic resonance imaging allows detection of synovitis, tenosynovitis, bursitis, and enthesitis as well as bone marrow edema and soft tissue edema. Several pediatric-specific MRI scoring systems have been developed and validated to standardize and facilitate the assessment of the extent of the inflammatory process and disease activity in MRI. Early detection of inflammatory changes allows the inclusion of comprehensive pharmacotherapy giving the possibility of permanent remission and objective measurement of the effectiveness of treatment.
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OBJECTIVES: To evaluate the pricing of etanercept (ETN) reference and biosimilar drugs in a changing competitive to monopolized market. METHODS: We conducted a comprehensive, retrospective analysis of ETN market competition, specifically changes in tender price based on shifts in market monopoly, including the effects on cost evolution, in the off-patent market in Poland. We included a total of 473 tenders for ETN purchase in dedicated biologic drug reimbursement programs, covering both pre-filled syringes and automatic injectors. This study covers the timeframe from November 2017 to December 2023, throughout which we evaluated a unique setting of ETN market re-monopolization from the perspective of payer, hospital and patient benefits resulting from changing cost calculations. RESULTS: Between 2017 and 2022, Erelzi was recorded as having the largest total tender volume (59%), with a mean price [per ETN daily defined dose (DDD)] of 7.28, followed by Enbrel (31%, 8.34) and Benepali (10%, 9.45), respectively. Over the last 6 months of waning market competition, the mean price for winning bids was estimated at 5.69. After market re-monopolization by an ETN biosimilar, the mean price of winning bids increased to 8.09, and continued to increase (9.71) in the last 6 months of available follow-up. In contrast to the competitive era, no significant relationship between tender volume and winning price was recorded after re-monopolization. In the most recent tenders, mean ETN prices increased up to 15.82, nearly tripling the lowest prices of the competitive market period. In the early re-monopolization market, mean annual treatment cost per patient is estimated at over 3800, which exceeds therapy costs in the prior competitive market years, and is expected to increase to over 6200 based on the most recent tenders. On a healthcare system level, this corresponds to over 3.42 million excess costs due to market monopoly. Higher ETN prices resulted in downstream failure of regulatory incentives to promote affordable biologics. Due to higher pricing, hospitals lost over an estimated 2.52 million, with possible risk of treatment restrictions. For the same reason, the public payer achieved comparable savings, allowing for partial coverage of higher reimbursement expenses. CONCLUSIONS: This nation-level scenario of market re-monopolization by a biosimilar drug confirms net loss and excess costs for the healthcare payer, as can be expected from economic theory. The upwards drug repricing and restriction of treatment availability occurs much more rapidly than the decrement in a period of market competition.
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Medicamentos Biossimilares , Custos de Medicamentos , Etanercepte , Medicamentos Biossimilares/economia , Etanercepte/economia , Etanercepte/uso terapêutico , Polônia , Humanos , Estudos Retrospectivos , Competição EconômicaRESUMO
To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013-2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients' gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.
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Antirreumáticos , Artrite Reumatoide , Humanos , Polônia/epidemiologia , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Masculino , Feminino , Incidência , Pessoa de Meia-Idade , Adulto , Idoso , Prevalência , Adolescente , Adulto Jovem , Antirreumáticos/uso terapêutico , Distribuição por Idade , Distribuição por Sexo , Criança , Pré-Escolar , Idoso de 80 Anos ou mais , LactenteRESUMO
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves, infection management in vulnerable populations requires formalized guidance. Although low-virulence variants of SARS-CoV-2 remain predominant, they pose an increased risk of severe illness in adults with rheumatic and musculoskeletal diseases (RMDs). Several disease-specific (chronic long-grade inflammation, concomitant immunosuppression) and individual (advanced age, multimorbidity, pregnancy, vaccination status) factors contribute to excess risk in RMD populations. Various post-COVID-19 manifestations are also increasingly reported and appear more commonly than in the general population. At a pathogenetic level, complex interplay involving innate and acquired immune dysregulation, viral persistence, and genetic predisposition shapes a unique susceptibility profile. Moreover, incident cases of SARS-CoV-2 infection as a trigger factor for the development of autoimmune conditions have been reported. Vaccination remains a key preventive strategy, and encouraging active education and awareness will be crucial for rheumatologists in the upcoming years. In patients with RMDs, COVID-19 vaccines' benefits outweigh the risks. Derivation of specialized diagnostic and therapeutic protocols within a comprehensive COVID-19 care plan represents an ideal scenario for healthcare system organization. Vigilance for symptoms of infection and rapid diagnosis are key for introducing antiviral treatment in patients with RMDs in a timely manner. This review provides updated guidance on optimal immunization, diagnosis, and antiviral treatment strategies.
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INTRODUCTION: By reducing treatment costs, biosimilars provide an opportunity to improve accessibility to highly effective drugs. OBJECTIVES: This study aimed to evaluate access to biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) among patients with rheumatic musculoskeletal diseases within a 10 year timeframe in Poland. PATIENTS AND METHODS: We performed a retrospective analysis using a nationwide public payer database. RESULTS: By 2022, 11 102, 6602, and 4400 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were treated with bDMARDs or JAKis. Peak drug utilization was observed for adalimumab, followed by etanercept and tocilizumab. Within the study timeframe, the estimated access to innovative drugs increased from 0.8%, 1.4%, and 0.8% to 3.2%, 8.7%, and 3.5% for RA, PsA, and axSpA patients, respectively. Affordable tumor necrosis factor inhibitors (TNFis) still predominate among innovative therapeutics, but their market share declined from 87% to 46%. The number of patients treated with other bDMARDs/JAKis almost doubled within the prespecified timeframe. Overall, the average annual treatment cost per patient decreased by 60%, from 7315 EUR to 2886 EUR. Despite recent safety warnings, JAKis appear to be increasingly utilized. Additional analyses regarding the COVID19 pandemic showed impaired access to intravenous therapies, but not subcutaneous or oral formulations. CONCLUSIONS: In Poland, biosimilarsrelated savings improved availability of higherpriced innovative drugs rather than less costly TNFis. Datadriven resource allocation and dedicated policy solutions facilitating access to affordable biologics are recommended.
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Antirreumáticos , Medicamentos Biossimilares , Inibidores de Janus Quinases , Doenças Reumáticas , Humanos , Polônia , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/economia , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Antirreumáticos/economia , Inibidores de Janus Quinases/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Produtos Biológicos/uso terapêutico , Produtos Biológicos/economia , Adulto , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Etanercepte/economiaRESUMO
The growing use of biological drugs in immune-mediated chronic diseases has undoubtedly revolutionized their treatment. Yet, the topic of vaccinations in this group of patients still raises many concerns and implies many therapeutic problems that require discussion and standardization of management. The aim of this literature review is to present current knowledge regarding safety and efficacy of vaccinations in dermatological and rheumatological patients treated with biological drugs and JAK inhibitors. Additionally, this article provides recommendation from experts of the Polish Dermatological Society about proper use of vaccinations during therapy with biologics. Generally, all live attenuated vaccines are contraindicated during immunosuppressive/immunomodulatory therapy. If there is need, they should be administered long enough prior to the therapy or after cessation. Yet, inactivated vaccines mostly can be safely used, but the problem in this case is the effectiveness of the vaccination. Most studies report that the immune response in patients on biologics after administration of different inactivated vaccines is similar to or even better than in the control group. Thus, the importance of vaccination among patients on biologics must be emphasized to reduce omissions and the fear of possible side effects or insufficient post-vaccination response.
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OBJECTIVES: CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. METHODS: Participants with eoJIA (2-17 years old), ERA or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. RESULTS: Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months' follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS: Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favourable. TRIAL REGISTRATION: ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).
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Antirreumáticos , Artrite Juvenil , Artrite Psoriásica , Neoplasias , Criança , Humanos , Adulto Jovem , Pré-Escolar , Adolescente , Etanercepte/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Resultado do Tratamento , Neoplasias/tratamento farmacológicoRESUMO
Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is a rare, inherited lysosomal storage disease. The disease is caused by deficiency of the lysosomal enzyme iduronate-2-sulphatase (I2S) due to mutations in the IDS gene, which leads to accumulation of glycosaminoglycans (GAGs). Deficiency of I2S enzyme activity in patients with MPS II leads to progressive lysosomal storage of GAGs in the liver, spleen, heart, bones, joints, and respiratory tract. This process disturbs cellular functioning and leads to multisystemic disease manifestations. Symptoms and their time of onset differ among patients. Diagnosis of MPS II involves assessment of clinical features, biochemical parameters, and molecular characteristics. Life-long enzyme replacement therapy with idursulfase (recombinant human I2S) is the current standard of care. However, an interdisciplinary team of specialists is required to monitor and assess the patient's condition to ensure optimal care. An increasing number of patients with this rare disease reach adulthood and old age. The transition from pediatric care to the adult healthcare system should be planned and carried out according to guidelines to ensure maximum benefit for the patient.
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BACKGROUND: Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy. METHODS: In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2. RESULTS: A total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population. CONCLUSIONS: Secukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis. TRIAL REGISTRATION NUMBER: NCT03031782.
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Antirreumáticos , Artrite Juvenil , Artrite Psoriásica , Adulto , Criança , Humanos , Adolescente , Artrite Juvenil/tratamento farmacológico , Antirreumáticos/efeitos adversos , Exacerbação dos Sintomas , Resultado do Tratamento , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/induzido quimicamente , Método Duplo-CegoRESUMO
Introduction: Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Material and methods: Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder ("overt CVD"), any traditional CV risk factor ("atCVrisk") and no CV risk factor ("vlCVrisk") groups. Results: Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk (n = 8, 4.2%) or overt CVD (n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02-1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04-1.18; p < 0.01), but not ever smoking (p = 0.93), male sex (p = 0.26), positive RF (p = 0.24), positive ACPA (p = 0.90), or baseline disease activity (p = 0.19), were independent predictor of incident CV risk factors. Conclusions: Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse long-term prognosis.
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Yersinia enterocolitica O:3 (YeO3) is considered to be associated with reactive arthritis (ReA), and its lipopolysaccharide (LPS) has been detected in synovial fluids from patients. Interestingly, YeO3 wild-type LPS was processed by host cells, resulting in truncated LPS molecules presenting the core region. Previously, we reported the immunogenicity but not adjuvanticity of YeO3 LPSs of wild (S) type, Ra, Rd, or Re chemotypes in mice. Here, we demonstrate the presence of YeO3 LPS chemotype-specific antibodies in all analyzed synovial fluids (SF) from patients with juvenile idiopathic arthritis (JIA). Interestingly, the high titer of antibodies specific for the Kdo-lipid A region was found in most tested SF. In contrast, only a few were positive for antibodies recognizing O-specific polysaccharides. Western blot analysis revealed the presence of antibodies reacting with fast-migrating LPS fractions and enterobacterial common antigen (ECA) in synovial fluid samples. Our data also suggest the importance of LPS-associated ECA for the antigenicity of endotoxin. Furthermore, we confirmed in vitro that Yersinia LPS processing leads to the exposure of its core region and enhanced potency of complement lectin pathway activation.
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Artrite Juvenil , Yersinia enterocolitica , Animais , Anticorpos/metabolismo , Antígenos de Bactérias , Lectinas/metabolismo , Lipídeo A , Lipopolissacarídeos , Camundongos , Antígenos O , Líquido SinovialRESUMO
INTRODUCTION: Achieving remission or lowdisease activity (LDA) is an integral principle of treattotarget (T2T) strategy in rheumatoid arthritis (RA). Prior studies have reported that achieving T2T therapeutic goals may be realistic only for a fraction of patients. Prospective, realworld data on achieving target disease control in ambulatory care populations are limited for Central and Eastern European countries. OBJECTIVES: The aim of the study was to analyze the efficacy of treatment and determine simple predictors of achieving T2T therapy goals in daily RA practice. PATIENTS AND METHODS: This multicenter, 6month study evaluated therapy outcomes and clinical characteristics of 791 consecutive RA outpatients, meeting the preset criteria of inadequate disease control. RESULTS: Only 9% of RA patients achieved remission or LAD after 3 months and 35% after 6 months. Achieving treatment targets after 6 months was associated with lower rates of pain, disability, presenteeism and absenteeism, which reflected improved quality of life. Provider views on adherence appeared discordant with patient claims, and did not predict target achievement. Never smoking, lower body mass index, and lower prednisone dose (<7.5 mg daily) were independently associated with a higher likelihood of achieving T2T therapeutic goals after 6 months. CONCLUSIONS: A combination of clinical characteristics and provider treatment decisions shapes the "profile" of a patient failing to achieve T2T goals. Lowdose steroid equivalent, never smoking, and lower body mass index appear as individual characteristics independently associated with achieving LDA / remission at 3 and 6 months.
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Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Prednisona/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Macrophage activation syndrome (MAS) is one of the few entities in rheumatology with the potential to quickly cause multiple organ failure and loss of life, and as such, requires urgent clinical intervention. It has a broad symptomatology, depending on the organs it affects. One especially dangerous aspect of MAS's course of illness is myocarditis leading to acute heart failure and possibly death. Research in recent years has proved that macrophages settled in different organs are not a homogenous group, with particular populations differing in both structure and function. Within the heart, we can determine two major groups, based on the presence of the C-C 2 chemokine receptor (CCR2): CCR2+ and CCR2-. There are a number of studies describing their function and the changes in the population makeup between normal conditions and different illnesses; however, to our knowledge, there has not been one touching on the matter of changes occurring in the populations of heart macrophages during MAS and their possible consequences. This review summarizes the most recent knowledge on heart macrophages, the influence of select cytokines (those particularly significant in the development of MAS) on their activity, and both the immediate and long-term consequences of changes in the makeup of specific macrophage populations-especially the loss of CCR2- cells that are responsible for regenerative processes, as well as the substitution of tissue macrophages by the highly proinflammatory CCR2+ macrophages originating from circulating monocytes. Understanding the significance of these processes may lead to new discoveries that could improve the therapeutic methods in the treatment of MAS.
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Insuficiência Cardíaca/imunologia , Síndrome de Ativação Macrofágica/complicações , Macrófagos/imunologia , Receptores CCR2/metabolismo , Progressão da Doença , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Humanos , Síndrome de Ativação Macrofágica/imunologia , Miocárdio/imunologiaRESUMO
INTRODUCTION: Real-world data indicate disparities in biologic access across Europe. OBJECTIVES: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. METHODS: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. RESULTS: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2-212; 32% < 4 weeks, 29% 5-12 weeks, 26% 13-28 weeks, 13% with >28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with "good" therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. CONCLUSIONS: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.
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The study aimed to evaluate the effect of retinoid treatment on the morphological changes in the nail apparatus in patients with nail psoriasis. MATERIAL AND METHODS: 41 patients aged 32 to 64 with nail psoriasis, without clinical signs of psoriatic arthritis, started on acitretin 0.6 to 0.8 mg kg b.w./d, for six months and 28 people in the control group were included in the study. Both groups had ultrasound examination of fingernails and digital extensor tendon in the distal interphalangeal joints. In psoriatic patients, US examination was conducted before starting the treatment and after six months. A total of 685 nails were examined. RESULTS: After six months of treatment, there was a reduction in the thickness of the nail bed and nail matrix (p = 0.046 and p = 0.031, respectively). The thickness of the nail plates decreased, although it was statistically insignificant (p = 0.059) and it was higher than in the control group (p = 0.034). The reduced severity of clinical nail changes after six months of retinoid treatment did not correlate with the reduction in extensor tendon thickness in any group of patients. CONCLUSIONS: In patients with nail psoriasis, acitretin treatment resulted in a rapid decrease in the thickness of the nail bed and matrix, but it did not affect the thickness of the nail plate after six months. There was no effect of acitretin on the digital extensor tendon thickness or the increased blood supply to the tendon area. The results of the study may indicate the usefulness of ultrasound nail examinations in patients with nail psoriasis not only to assess the advancement of morphological changes and response to treatment, but also to choose the potential treatment.
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OBJECTIVE: To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure. RESULTS: Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years. CONCLUSION: Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Infecções/epidemiologia , Adolescente , Artrite Juvenil/fisiopatologia , Bronquite/epidemiologia , Celulite (Flegmão)/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Varicela/epidemiologia , Criança , Pré-Escolar , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Metotrexato/administração & dosagem , Medidas de Resultados Relatados pelo Paciente , Pneumonia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase, which is caused by mutations in the arylsulphatase B (ARSB) gene. To date, 163 different types of mutations in the ARSB have been reported. However, the full mutation spectrum in the MPS VI phenotype is still not known. The aim of this study was to perform molecular testing of the ARSB gene in the patient and his family members to confirm MPS VI. METHODS: Molecular characterisation of the ARSB gene was performed using Sanger sequencing. We studied a child suspected of having MPS VI and 16 other relatives. RESULTS: We identified a C-to-T transition resulting in an exchange of the Arg codon 160 for a premature stop codon (R160*, in exon 2). The transition was in CpG dinucleotides. INTERPRETATION AND CONCLUSIONS: The study provided some insights into the genotype-phenotype relationship in MPS VI and the importance of genetic testing when diagnosing MPS, which is not a mandatory test for the diagnosis and only very occasionally performed. Additionally, we present here the history of a family with confirmed MPS VI, which is extremely rare especially in south-eastern Poland. What is more, the position where the mutation is located is very interesting because it is the region of CpG, which is the site of the methylation process. Thus, this opens the possibility of a new approach indicating the involvement of an epigenetic mechanism that should be examined in the context of the pathomechanism of MPS.
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Immune-mediated inflammatory diseases are a group of diseases characterized by generalized inflammation that results from immune dysregulation, especially involving the mechanisms of acquired immunity. These diseases may be familial, showing that genetic factors play an important role in their development. Additionally, the occurrence of one disease makes a patient prone to other diseases. However, the coexistence of systemic lupus erythematosus (SLE) and psoriasis (Ps) is very rare due to their distinct genetic determinants and mechanisms of pathogenesis. Treatment is also challenging, as medications used to treat one condition exacerbate or even trigger the symptoms of the other. This paper presents the case of a Ps patient with a family history of autoimmune diseases, who developed systemic lupus erythematosus during puberty, as well as a discussion on the coexistence of SLE and Ps in developmental age based on available literature searching for PubMed database and American College of Rheumatology and European League Against Rheumatism abstracts particularly in this subject.
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Vasculitides are a diverse group of diseases. The potential diversity of their clinical symptoms requires the exclusion of other systemic connective tissue diseases, infectious diseases or malignancies. Due to similar clinical manifestations, comprehensive differential diagnosis is needed. This paper presents the case of a boy in whom polyarteritis nodosa, early stage of Behçet's disease or autoimmune/autoinflammatory syndrome induced by adjuvants was suspected following initial diagnostics. He was ultimately diagnosed with cutaneous polyarteritis nodosa.
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Rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) make up a group of chronic immune-mediated inflammatory diseases (IMIDs). The course of these diseases involves chronic inflammation of joints and enthesopathies, which can result in joint damage and disability. Microparticles (MPs) are a group of small spherical membranous vesicles. The structure and cellular origin of MPs, mechanisms that stimulate their secretion and the place of their production, determine their biological properties, which could become manifest in the pathogenesis of immune-mediated inflammatory diseases. Microparticles can stimulate synovitis with proinflammatory cytokines and chemokines. MPs may also contribute to the pathogenesis of rheumatic diseases by the formation of immune complexes and complement activation, pro-coagulation activity, activation of vascular endothelium cells, and stimulation of metalloproteinase production. It seems that in the future, microparticles can become a modern marker of disease activity, a response to treatment, and, possibly, they can be used in the prognosis of the course of arthritis. The knowledge of the complexity of MPs biology remains incomplete and it requires further comprehensive studies to explain how they affect the development of rheumatic diseases. This review focuses on the immunopathogenic and therapeutic role of MPs in chronic immune-mediated inflammatory joint diseases.