RESUMO
BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. METHOD: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. RESULT: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. CONCLUSION: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks.
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Artrite Reumatoide , Medicamentos Biossimilares , Reumatologia , Humanos , Rituximab , Medicamentos Biossimilares/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pacientes Ambulatoriais , Noruega , Preparações FarmacêuticasRESUMO
OBJECTIVES: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. METHODS: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. RESULTS: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. CONCLUSIONS: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.
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Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Infecções/epidemiologia , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Feminino , Humanos , Incidência , Infecções/induzido quimicamente , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Noruega/epidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de RegressãoRESUMO
BACKGROUND: In Norway, an annual tender system for the prescription of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) has been used since 2007. This study aimed to explore annual b/tsDMARDs costs and disease outcomes in Norwegian rheumatoid arthritis (RA) patients between 2010 and 2019 under the influence of the tender system. METHODS: RA patients monitored in ordinary clinical practice were recruited from 10 Norwegian centers. Data files from each center for each year were collected to explore demographics, disease outcomes, and the prescribed treatment. The cost of b/tsDMARDs was calculated based on the drug price given in the annual tender process. RESULTS: The number of registered RA patients increased from 4909 in 2010 to 9335 in 2019. The percentage of patients receiving a b/tsDMARD was 39% in 2010 and 45% in 2019. The proportion of b/tsDMARDs treated patients achieving DAS28 remission increased from 42 to 67%. The estimated mean annual cost to treat a patient on b/tsDMARDs fell by 47%, from 13.1 thousand euros (EUR) in 2010 to 6.9 thousand EUR in 2019. The mean annual cost to treat b/tsDMARDs naïve patients was reduced by 75% (13.0 thousand EUR in 2010 and 3.2 thousand EUR in 2019). CONCLUSIONS: In the period 2010-2019, b/tsDMARD treatment costs for Norwegian RA patients were significantly reduced, whereas DAS28 remission rates increased. Our data may indicate that the health authorities' intention to reduce treatment costs by implementing a tender system has been successful.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Preparações Farmacêuticas , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Custos de Medicamentos , Humanos , PrescriçõesRESUMO
BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Hidroxicloroquina/uso terapêutico , Carga Viral/efeitos dos fármacos , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Anticorpos Antivirais/sangue , Biomarcadores/sangue , COVID-19/complicações , COVID-19/mortalidade , Causas de Morte , Feminino , Mortalidade Hospitalar , Humanos , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Orofaringe/virologia , Insuficiência Respiratória/virologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Padrão de Cuidado , Resultado do TratamentoRESUMO
BACKGROUND: Studies exploring risk factors for ankle fractures in adults are scarce, and with diverging conclusions. This study aims to investigate whether overweight, obesity and osteoporosis may be identified as risk factors for ankle fractures and ankle fracture subgroups according to the Danis-Weber (D-W) classification. METHODS: 108 patients ≥40 years with fracture of the lateral malleolus were included. Controls were 199 persons without a previous fracture history. Bone mineral density of the hips and spine was measured by dual-energy x-ray absorptiometry, and history of previous fracture, comorbidities, medication, physical activity, smoking habits, body mass index and nutritional factors were registered. RESULTS: Higher body mass index with increments of 5 gave an adjusted odds ratio (OR) of 1.30 (95% confidence interval (CI) 1.03-1.64) for ankle fracture, and an adjusted OR of 1.96 (CI 0.99-4.41) for sustaining a D-W type B or C fracture compared to type A. Compared to patients with normal bone mineral density, the odds of ankle fracture in patients with osteoporosis was 1.53, but the 95% CI was wide (0.79-2.98). Patients with osteoporosis had reduced odds of sustaining a D-W fracture type B or C compared to type A (OR 0.18, CI 0.03-0.83). CONCLUSIONS: Overweight increased the odds of ankle fractures and the odds of sustaining an ankle fracture with possible syndesmosis disruption and instability (D-W fracture type B or C) compared to the stable and more distal fibula fracture (D-W type A). Osteoporosis did not significantly increase the odds of ankle fractures, thus suffering an ankle fracture does not automatically warrant further osteoporosis assessment.
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Fraturas do Tornozelo , Osteoporose , Absorciometria de Fóton , Adulto , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/epidemiologia , Densidade Óssea , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologiaRESUMO
Importance: Proactive therapeutic drug monitoring (TDM), defined as individualized drug dosing based on scheduled monitoring of serum drug levels, has been proposed as an alternative to standard therapy to maximize efficacy and safety of infliximab and other biological drugs. However, whether proactive TDM improves clinical outcomes when implemented at the time of drug initiation, compared with standard therapy, remains unclear. Objective: To assess whether TDM during initiation of infliximab therapy improves treatment efficacy compared with standard infliximab therapy without TDM. Design, Setting, and Participants: Randomized, parallel-group, open-label clinical trial of 411 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis initiating infliximab therapy in 21 hospitals in Norway. Patients were recruited from March 1, 2017, to January 10, 2019. Final follow-up occurred on November 5, 2019. Interventions: Patients were randomized 1:1 to receive proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 207) or standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 204). Main Outcomes and Measures: The primary end point was clinical remission at week 30. Results: Among 411 randomized patients (mean age, 44.7 [SD, 14.9] years; 209 women [51%]), 398 (198 in the TDM group and 200 in the standard therapy group) received their randomized intervention and were included in the full analysis set. Clinical remission at week 30 was achieved in 100 (50.5%) of 198 and 106 (53.0%) of 200 patients in the TDM and standard therapy groups, respectively (adjusted difference, 1.5%; 95% CI, -8.2% to 11.1%; P = .78). Adverse events were reported in 135 patients (68%) and 139 patients (70%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance: Among patients with immune-mediated inflammatory diseases initiating treatment with infliximab, proactive therapeutic drug monitoring, compared with standard therapy, did not significantly improve clinical remission rates over 30 weeks. These findings do not support routine use of therapeutic drug monitoring during infliximab induction for improving disease remission rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.
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Artrite/tratamento farmacológico , Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adulto , Doença Crônica , Relação Dose-Resposta a Droga , Feminino , Humanos , Quimioterapia de Indução , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Indução de Remissão , Padrão de CuidadoRESUMO
Importance: Proactive therapeutic drug monitoring (TDM), consisting of individualized treatment based on scheduled assessments of serum drug levels, has been proposed as an alternative to standard therapy to optimize efficacy and safety of infliximab and other biologic drugs. However, it remains unclear whether proactive TDM improves clinical outcomes during maintenance therapy. Objective: To assess whether proactive TDM during maintenance therapy with infliximab improves treatment efficacy by preventing disease worsening compared with standard infliximab therapy without TDM. Design, Setting, and Participants: Randomized, parallel-group, open-label clinical trial including 458 adults with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease, or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospitals. Patients were recruited from June 7, 2017, to December 12, 2019. Final follow-up took place on December 14, 2020. Interventions: Patients were randomized 1:1 to proactive TDM with dose and interval adjustments based on scheduled monitoring of serum drug levels and antidrug antibodies (TDM group; n = 228) or to standard infliximab therapy without drug and antibody level monitoring (standard therapy group; n = 230). Main Outcome and Measures: The primary outcome was sustained disease control without disease worsening, defined by disease-specific composite scores or consensus about disease worsening between patient and physician leading to a major change in treatment (switching to another biologic drug, adding an immunosuppressive drug including glucocorticoids, or increasing the infliximab dose), during the 52-week study period. Results: Among 458 randomized patients (mean age, 44.8 [SD, 14.3] years; 216 women [49.8%]), 454 received their randomly allocated intervention and were included in the full analysis set. The primary outcome of sustained disease control without disease worsening was observed in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group. The estimated adjusted difference was 17.6% (95% CI, 9.0%-26.2%; P < .001) favoring TDM. Adverse events were reported in 137 patients (60%) and 142 patients (63%) in the TDM and standard therapy groups, respectively. Conclusions and Relevance: Among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening. Further research is needed to compare proactive TDM with reactive TDM, to assess the effects on long-term disease complications, and to evaluate the cost-effectiveness of this approach. Trial Registration: ClinicalTrials.gov Identifier: NCT03074656.
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Artrite/tratamento farmacológico , Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Algoritmos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Padrão de Cuidado , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
BACKGROUND: It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures. METHODS: In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex). RESULTS: Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture. CONCLUSIONS: Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention.
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Doenças Ósseas Metabólicas , Osteoporose , Fraturas do Rádio , Absorciometria de Fóton , Idoso , Densidade Óssea , Humanos , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/epidemiologiaRESUMO
BACKGROUND: Patients with celiac disease (CD), including adults with subclinical disease, have low bone mineral density (BMD), deteriorated bone microarchitecture and meta-analysis show an increased risk of fracture. Immunoglobulin A (IgA) against transglutaminase 2 (IgA TG2) is a highly reliable marker to detect CD. MAIN OBJECTIVE: To explore the prevalence of positive IgA TG2 and CD in patients with distal radius and ankle fracture compared to community-based controls. METHODS: Four hundred patients aged 40 years or above with distal fractures were included in a case-control study. About 197 controls were identified from the National Population Registry, those included had never suffered a fracture. BMD was measured, and comorbidities, medications, physical activity, smoking habits, body mass index (BMI) and nutritional factors were registered. Blood analysis to detect common causes of secondary osteoporosis was performed. RESULTS: About 2.5% of the fracture patients had positive IgA TG2, compared to 1% in the control group. The odds ratio, adjusted for sex and age, of having positive IgA TG2 was 2.50 (95% CI 0.54-11.56). CONCLUSIONS: There were no significantly increased odds of CD in adult patients with fractures compared to controls; however, results imply that positive IgA TG2 is more prevalent in fracture patients than in controls. This study indicates that universal screening for CD in fracture patients is not warranted, but supports current clinical practice in Norway to suspect and investigate for CD in patients with fracture, osteoporosis and other risk factors for CD.
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Fraturas do Tornozelo/sangue , Doença Celíaca/complicações , Proteínas de Ligação ao GTP/imunologia , Imunoglobulina A/sangue , Transglutaminases/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Noruega , Osteoporose/complicações , Proteína 2 Glutamina gama-Glutamiltransferase , Fatores de RiscoRESUMO
Aortitis of ascending aorta is a recognized complication of ankylosing spondylitis (AS). There are a few published cases of diffuse aortitis and aorta collaterals inflammation that fulfill Takayasu's arteritis (TA) criteria coexisting with AS. We have reviewed published cases from literature and present three new cases of such coexistence. We identified three patients who fulfilled definite AS New York criteria in our Takayasu's vasculitis cohort of eight patients. One of this patients had been diagnosed with Crohn's disease before AS and TA diagnosis. Additionally, two other patients had an inflammatory back pain and suffered of chronic uveitis. One of them had increased sacroiliac uptake of isotope in scintigraphy. Those two patients did not fulfil spondyloarthritis criteria. In this paper, we debate if TA type arteritis might be one of the AS cardiovascular complications.
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Espondilite Anquilosante/complicações , Arterite de Takayasu/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/patologia , Arterite de Takayasu/patologiaRESUMO
Objectives: MTX, LEF and SSZ are conventional synthetic DMARDs (csDMARDs) with a well-established role in the treatment of RA. We aimed to estimate and compare the relative risks for adverse events (AEs) and the discontinuation of these drugs owing to AEs. Methods: We included all 3339 patients from the NOR-DMARD study treated with MTX, LEF or SSZ in monotherapy. All reported AEs were compared between treatment groups using quasi-Poisson regression. In addition, drug retention rates were analysed using Kaplan-Meier estimates with Cox regression to control for possible confounders. We analysed drug retention rates and cumulative risk of discontinuation attributable to AEs using the Kaplan-Meier estimator. We assessed age, sex, baseline DAS in 28 joints with ESR (DAS28-ESR), seropositivity, prednisolone use, previous DMARD use, year of inclusion and co-morbidity as possible cofounders. Results: We found that the discontinuation rate attributable to AEs was significantly higher for LEF and SSZ than for MTX. After the first year, it was 13.7% (95% CI 12.2, 15.2), 39.6% (95% CI 34.8, 44) and 43.4% (95% CI 38.2, 48.1) for MTX, SSZ and LEF, respectively. Similar results were found when adjusting for confounders. The overall AEs were comparable across the treatment groups. The AE profile was as expected for each drug. Conclusion: Our work has shown a similar AE profile of csDMARDs to previous data. However, higher discontinuation rates for SSZ and LEF cannot be explained easily from AE profiles.
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OBJECTIVE: To compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA). METHODS: Adult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated. RESULTS: We identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6). CONCLUSION: TNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.
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Antirreumáticos , Artrite Juvenil , Artrite Reumatoide , Humanos , Adulto , Metotrexato/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/induzido quimicamente , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Resultado do Tratamento , Fator de Necrose Tumoral alfa , Artrite Reumatoide/tratamento farmacológico , Quimioterapia CombinadaRESUMO
Cytokines are implied in polymyositis/dermatomyositis (PM/DM) pathogenesis. Our aim was to evaluate the serum levels of interleukin-15 (IL-15), soluble receptors for IL-2 (sIL-2R) and TNF-alpha type 1 receptor (sTNF-R1) in PM/DM patients and their relation to disease activity and clinical symptoms. Thirty-eight patients who met definite or probable criteria of Bohan and Peter for DM/PM were included into the study. Results in patients with active (41 observations) and inactive disease (24 observations) were compared with control (15 subjects). The median level of IL-15 was 47.6 ± 170 pg/ml in active patients, 25.15 ± 240 pg/ml in inactive and 28.5 ± 28.89 pg/ml in controls. We demonstrated significant differences between active patients and controls in levels of IL-15 (0.016, 95%CI 1.39-57.1). The median level of sIL-2R was 314 ± 388, 235.3 ± 269 and 144.3 ± 152.9 pg/ml, and the median level of sTNF-R1 was 350 ± 388; 294.7 ± 204.7; 209.5 ± 105.9 pg/ml in active, inactive and control subjects, respectively. There were significantly higher serum levels of these cytokines in active patients than in control subjects (for sIL-2R P = 0.05, CI95% 0.4-331; and sTNF-R1 P = 0.031, CI95% 15.1-321.5). The interleukin levels did not differ between inactive patients and controls. Elevation of IL-15, sIL2-R and sTNF-R1 in active patients provides preliminary evidence for the activation of inflammatory response during PM/DM flares. Further studies may be needed to explain the mechanisms driving these diseases.
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Dermatomiosite/sangue , Interleucina-15/sangue , Receptores de Interleucina-2/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Biomarcadores/sangue , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Pessoa de Meia-Idade , Dermatopatias/sangue , Dermatopatias/complicações , Dermatopatias/diagnósticoRESUMO
OBJECTIVE: The objective of this study was to compare the efficacy and safety of rituximab in older vs younger patients with rheumatoid arthritis. METHODS: Data on 367 patients with rheumatoid arthritis treated with rituximab in the Norwegian Disease-Modifying Antirheumatic Drug (NOR-DMARD) register were analysed, comparing patients aged ≥ 65 years (n = 91) with patients aged < 65 years (n = 276). Drug survival was compared using a Kaplan-Meier analysis and Cox proportional hazard models. Disease activity, as assessed by the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) and the Simplified Disease Activity Index, was analysed with linear mixed models. The occurrence of adverse events was analysed by quasi-Poisson regression models. RESULTS: Drug survival was similar in the two age groups. The proportion of patients who remained taking rituximab over 2 years was 72% in those under aged 65 years vs 74% in those aged ≥ 65 years. No statistically significant association with age was found for drug survival in either the unadjusted (hazard ratio 1.13, p = 0.65) or adjusted Cox proportional hazard analyses for the model with DAS28-ESR as a confounder (effect size 1.11, p = 0.73). Models including the Simplified Disease Activity Index instead of DAS28-ESR yielded similar results. Age was furthermore not significantly associated with disease activity over time, although there was a tendency towards a poorer response in older patients. In the older age group, there was a higher incidence of pneumonia (107 vs 51 per 1000 patient-years) and other serious infections (142 vs 66 per 1000 patient-years). CONCLUSIONS: Rituximab is a reasonable therapeutic option for older patients with rheumatoid arthritis although vigilance is needed with regard to the infection profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01581294.
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Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunossenescência/efeitos dos fármacos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Adulto , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Sistema de Registros , Rituximab/administração & dosagem , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Ultrasound is widely used in the diagnosis and follow-up of chronic arthritis. We present an evaluation of a novel automatic ultrasound diagnostic tool based on image recognition technology. Methods used in developing the algorithm are described elsewhere. For the purpose of evaluation, we collected 140 ultrasound images of metacarpophalangeal and proximal interphalangeal joints from patients with chronic arthritis. They were classified, according to hypertrophy size, into four stages (0-3) by three independent human observers and the algorithm. An agreement ratio was calculated between all observers and the standard derived from results of human staging using κ statistics. Results was significant in all pairs, with the highest p value of 3.9 × 10-6. κ coefficients were lower in algorithm/human pairs than between human assessors. The algorithm is effective in staging synovitis hypertrophy. It is, however, not mature enough to use in a daily practice because of limited accuracy and lack of color Doppler recognition. These limitations will be addressed in the future.
Assuntos
Artrite/complicações , Articulações/diagnóstico por imagem , Aprendizado de Máquina , Sinovite/diagnóstico por imagem , Ultrassonografia/métodos , Artrite/diagnóstico por imagem , Artrite/patologia , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/patologia , Humanos , Articulações/patologia , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação Metacarpofalângica/patologia , Reprodutibilidade dos Testes , Sinovite/complicações , Sinovite/patologia , Articulação do Dedo do Pé/diagnóstico por imagem , Articulação do Dedo do Pé/patologiaRESUMO
Identifying the separate parts in ultrasound images such as bone and skin plays a crucial role in the synovitis detection task. This paper presents a detector of bone and skin regions in the form of a classifier which is trained on a set of annotated images. Selected regions have labels: skin or bone or none. Feature vectors used by the classifier are assigned to image pixels as a result of passing the image through the bank of linear and nonlinear filters. The filters include Gaussian blurring filter, its first and second order derivatives, Laplacian as well as positive and negative threshold operations applied to the filtered images. We compared multiple supervised learning classifiers including Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and Support Vector Machines (SVM) with various kernels, using four classification performance scores and computation time. The Random Forest classifier was selected for the final use, as it gives the best overall evaluation results.
RESUMO
The idiopathic inflammatory myopathies are a heterogeneous group of diseases that can involve various systems. Antibodies directed against aminoacyl-tRNA synthetases, such as anti-Jo-1 antibodies, are strongly associated with a syndrome which consists of myositis, interstitial lung disease (ILD), arthritis and Raynaud's phenomenon. Forty-one patients with various forms of idiopathic inflammatory myopathies were assessed: 14 patients with anti-Jo-1 antibodies and 27 patients without anti-Jo-1 antibodies as a control group. We retrospectively analysed clinical symptoms, treatment and outcome in both groups. Patients with anti-Jo-1 antibodies more often had ILD (64.2 vs. 11.1%), arthritis (64.2 vs. 18.1%) and Raynaud's phenomenon (38 vs. 0%). Patients without the anti-Jo-1 antibody presented worse muscle strength and more frequently myalgia (37 vs. 21%), cutaneous rash (18.5 vs. 7%), heliotrope rash (29% vs. 7%) and periungueal changes (22 vs. 0%) than the anti-Jo-1-positive patients. Outcome was good in both groups. Improvement was achieved in the 14 (100%) Jo-1 positive patients, and in 25 (92.5%) controls. Two (7.5%) patients from control group achieved remission.
Assuntos
Anticorpos Antinucleares/sangue , Miosite/diagnóstico , Artrite/diagnóstico , Artrite/fisiopatologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Miosite/imunologia , Miosite/fisiopatologia , Prognóstico , Doença de Raynaud/diagnóstico , Doença de Raynaud/fisiopatologia , Estudos RetrospectivosRESUMO
In recent years new potential therapies of systemic lupus erythematosus, called biological therapies, have been developed. These agents influence some immunological reactions, essential for genesis of systemic lupus erythematosus, ie. T cells and B cells activation, antibodies production, cytokines and complement components activation. Pathogenic basis of using these therapies, their safety and efficacy assessment have been presented.
Assuntos
Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Imunoterapia/tendências , Lúpus Eritematoso Sistêmico/terapia , Complexo Antígeno-Anticorpo/metabolismo , Ativação do Complemento/efeitos dos fármacos , Citocinas/farmacologia , Citocinas/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
The connection between scleroderma and lymphoma is uncommon and its pathogenic relationship is a much debated subject. We describe the case of a patient with mucosa-associated lymphoid tissue lymphoma (MALT) of both parotid glands without clinical signs of Sjögren's syndrome who simultaneously developed scleroderma. Independently of the pathogenic mechanism of these two diseases, it seems very important to emphasize that scleroderma may be the first manifestation of lymphoma.