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BACKGROUND: Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. AIMS: To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. METHODS: We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. RESULTS: For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. CONCLUSION: Methotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.
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OBJECTIVES: Clinical inertia, or therapeutic inertia (TI), is the medical behaviour of not initiating or intensifying treatment when recommended by clinical recommendations. To our knowledge, our survey is the first to assess TI around psoriatic arthritis (PsA). METHODS: Eight hundred and twenty-five French rheumatologists were contacted via email between January and March 2021 and invited to complete an online questionnaire consisting of seven clinical vignettes: five cases ('oligoarthritis', 'enthesitis', 'polyarthritis', 'neoplastic history', 'cardiovascular risk') requiring treatment OPTImization, and two 'control' cases (distal interphalangeal arthritis, atypical axial involvement) not requiring any change of treatment-according to the most recent PsA recommendations. Rheumatologists were also questioned about their routine practice, continuing medical education and perception of PsA. RESULTS: One hundred and one rheumatologists completed this OPTI'PsA survey. Almost half the respondents (47%) demonstrated TI on at least one of the five vignettes that warranted treatment optimization. The complex profiles inducing the most TI were 'oligoarthritis' and 'enthesitis' with 20% and 19% of respondents not modifying treatment, respectively. Conversely, clinical profiles for which there was the least uncertainty ('polyarthritis in relapse', 'neoplastic history' and 'cardiovascular risk') generated less TI with 11%, 8% and 6% of respondents, respectively, choosing not to change the current treatment. CONCLUSION: The rate of TI we observed for PsA is similar to published data for other chronic diseases such as diabetes, hypertension, gout or multiple sclerosis. Our study is the first to show marked clinical inertia in PsA, and further research is warranted to ascertain the reasons behind this inertia.
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Artrite Psoriásica , Entesopatia , Hipertensão , Humanos , Estudos Prospectivos , Reumatologistas , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sjögren's syndrome-related non-Hodgkin lymphoma (primary SS-NHL). METHODS: Peripheral whole blood samples were collected from 345 well-phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i-primary SS-NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS-NHL, including those with a history of lymphoma (h-primary SS-NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group. RESULTS: Twenty-one patients with primary SS-NHL (including 8 with i-primary SS-NHL and 13 h-primary SS-NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell-related genes. Bruton's tyrosine kinase (BTK) and a proliferation-inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up-regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS. CONCLUSION: BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS-NHL requires confirmation in other prospective cohorts.
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Linfoma , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Tirosina Quinase da Agamaglobulinemia/genética , Estudos Prospectivos , Linfoma/genética , Linfoma/complicações , Fatores de RiscoRESUMO
OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.
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Doenças Autoimunes , COVID-19 , Adolescente , Feminino , Humanos , Pessoa de Meia-Idade , Interleucina-23 , Uso Off-Label , Estudos Prospectivos , Sistema de RegistrosRESUMO
OBJECTIVES: To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). METHODS: Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. RESULTS: A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. CONCLUSION: Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability.
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Lúpus Eritematoso Sistêmico , Médicos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Estrogênios , Fadiga/diagnóstico , Fadiga/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estados UnidosRESUMO
OBJECTIVE: Among the most significant challenges in SLE are the excessive diagnosis delay and the lack of coordinated care. The aim of the study was to investigate patient pathways in SLE in order to improve clinical and organisational challenges in the management of those with suspected and confirmed SLE. METHODS: We conducted a cross-sectional study of patients with SLE, healthcare providers and other representative stakeholders. Focus groups were conducted, and based on the collected data the most impactful disruption points in SLE patient pathways were identified. A novel framework to improve individual patient pathways in SLE was developed, discussed and validated during a consensus meeting with representative stakeholders. RESULTS: Six thematic clusters regarding disruption in optimal patient pathways in SLE were identified: appropriate and timely referral strategy for SLE diagnosis; the need for a dedicated consultation during which the diagnosis of SLE would be announced, and following which clarifications and psychological support offered; individualised patient pathways with coordinated care based on organ involvement, disease severity and patient preference; improved therapeutic patient education; prevention of complications such as infections, osteoporosis and cancer; and additional patient support. During the consensus meeting, the broader panel of stakeholders achieved consensus on these attributes and a framework for optimising SLE patient pathways was developed. CONCLUSIONS: We have identified significant disruption points and developed a novel conceptual framework to improve individual patient pathways in SLE. These data may be of valuable interest to patients with SLE, their physicians, health organisations as well as policy makers.
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Lúpus Eritematoso Sistêmico , Estudos Transversais , Grupos Focais , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. METHODS: From 2003 to 2005, 813 patients were included if they had early arthritis (<6 months) with a high probability of RA and had never been prescribed DMARDs. Multivariate analysis was used to evaluate predictors of outcome. RESULTS: In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. CONCLUSIONS: We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Artrite Reumatoide/epidemiologia , Comorbidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
BACKGROUND: Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE. METHODS: This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS). RESULTS: Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4). CONCLUSIONS: A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01738360 registered 30 November 2012.
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Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Adulto , Trióxido de Arsênio , Humanos , Imunossupressores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Upon recognition of microbial DNA or self-DNA, the cyclic-GMP-AMP synthase (cGAS) of the host catalyzes the production of the cyclic dinucleotide cGAMP. cGAMP is the main activator of STING, stimulator of interferon genes, leading to interferon synthesis through the STING-TBK1-IRF3 pathway. STING is also a hub for activation of NF-κB and autophagy. The present review details the striking similarities between T and B cell responses in severe coronavirus disease 2019 (COVID-19) and both animal or human models of STING gain of function (SAVI syndromes: STING-associated vasculopathy with onset in infancy). Those similarities may be further clues for a delayed activation of STING in severe COVID-19 patients, due to DNA damages following severe acute respiratory syndrome coronaviruses (SARS-CoV-2) infection and unusual role of STING in SARS-CoV-2 control. In early stages, Th2 differentiation are noticed in both severe COVID-19 and SAVI syndromes; then, CD4+ and CD8+ T cells functional exhaustion/senescent patterns due to TCR hyper-responsiveness are observed. T cell delayed over-responses can contribute to pneumonitis and delayed cytokine secretion with over-production of IL-6. Last, STING over-activation induces progressive CD4+ and CD8+ T lymphopenia in SAVI syndromes, which parallels what is observed in severe COVID-19. ACE2, the main receptor of SARS-CoV-2, is rarely expressed in immune cells, and it has not been yet proven that some human lymphocytes could be infected by SARS-CoV-2 through CD147 or CD26. However, STING, expressed in humans T cells, might be triggered following excessive transfer of cGAMP from infected antigen presenting cells into activated CD4+ and CD8+ T cells lymphocytes. Indeed, those lymphocytes highly express the cGAMP importer SLC19A1. Whereas STING is not expressed in human B cells, B cells counts are much less affected, either in COVID-19 or SAVI syndromes. The recognition of delayed STING over-activation in severe COVID-19 patients could prompt to target STING with specific small molecules inhibitors already designed and/or aspirin, which inhibits cGAS.
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Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Proteínas de Membrana/imunologia , SARS-CoV-2/imunologia , Células Th2/imunologia , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Linfócitos B/patologia , Basigina/imunologia , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Dipeptidil Peptidase 4/imunologia , Humanos , Fator Regulador 3 de Interferon/imunologia , Nucleotidiltransferases/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Transdução de Sinais/imunologia , Células Th2/patologiaRESUMO
OBJECTIVES: To assess the efficacy and tolerance profile of rituximab in rheumatoid arthritis (RA)-associated large granular lymphocyte leukemia (LGLL). METHODS: Multicenter retrospective case series. Inclusion criteria were RA defined by the ACR/EULAR 2010 criteria and LGLL defined by absolute LGL count ≥ 0.3â¯×â¯109/L with evidence of an expanded clonal LGL population (flow cytometry, TCR-γ polymerase chain reaction, or Stat3 mutation). RESULTS: Fourteen patients (10 women, mean age 55.2 ± 14.2 years) included; 13 were seropositive for anti-cyclic citrullinated peptides (nâ¯=â¯11) or rheumatoid factor (nâ¯=â¯10). LGLL diagnosis was made 9.5 [IQR: 3.25;15.5] years after RA diagnosis. Thirteen patients had T-LGLL. Rituximab was the first-line therapy for LGLL for 4 patients. Previous treatment lines included methotrexate (nâ¯=â¯7), cyclophosphamide (nâ¯=â¯2), cyclosporin A (nâ¯=â¯1), or granulocyte colony-stimulating factor (nâ¯=â¯4). Rituximab was used in monotherapy (nâ¯=â¯8) or associated to methotrexate (nâ¯=â¯3), granulocyte colony-stimulating factor (nâ¯=â¯2), or alkylating agents (nâ¯=â¯1). The number of rituximab cycles ranged from 1 to 11 (median 6), with high heterogeneity in dosing regimens. Median duration response after rituximab initiation was 35 [IQR: 23.5;41] months. The overall response rate was 100%: 8 patients experienced complete response (normalization of blood count and LGL ≤ 0.3â¯×â¯109/L) and 6 experienced partial responses (improvement in blood counts without complete normalization). The tolerance profile was good, with no infectious complications. CONCLUSION: rituximab appears as a valuable therapeutic option for RA-associated LGLL.
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Artrite Reumatoide , Leucemia Linfocítica Granular Grande , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Leucemia Linfocítica Granular Grande/tratamento farmacológico , Metotrexato , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
BACKGROUND: Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). OBJECTIVE: To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT02433522). SETTING: 39 clinical centers in France. PATIENTS: 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy. INTERVENTION: Rituximab or placebo infusion every 6 months for 18 months (4 infusions). MEASUREMENTS: The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0. RESULTS: From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (P = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group. LIMITATION: Potential selection bias based on previous rituximab response and tolerance. CONCLUSION: Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy. PRIMARY FUNDING SOURCE: French Ministry of Health and Hoffmann-La Roche.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Rituximab/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities. METHODS: Prospective, randomized, controlled, open, 12-month trial (NCT02374749). PARTICIPANTS: consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist) THE PROGRAM: A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit. TREATMENT ALLOCATION: random allocation (i.e. either this program or an educational program not presented here and considered here as the control group). MAIN OUTCOME: change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management). RESULTS: 502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p<0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p<0.01). CONCLUSIONS AND RELEVANCE: This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.
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Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática em Enfermagem/organização & administração , Espondilite Anquilosante/enfermagem , Adulto , Comorbidade , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , AutogestãoRESUMO
OBJECTIVE: The randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter's titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12. METHODS: MAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free survival rates in each arm as primary end points. Exploratory subgroup analyses were run according to CYC or rituximab induction and newly diagnosed or relapsing AAV. RESULTS: At M3, M6, M9 and M12, respectively, among the 161 patients included, 79/80 (98.8%), 76/80 (95%), 74/80 (92.5%) and 73/80 (91.3%) from D0, and 80/81 (98.8%), 78/81 (96.3%), 76/81 (93.8%) and 76/81 (93.8%) from D0+D14 groups were alive and relapse-free. No between-group differences were observed. Results were not affected by CYC or rituximab induction, or newly diagnosed or relapsing AAV. CONCLUSIONS: We were not able to detect a difference between the relapse-free survival rates for up to M12 for the D0 and D0+D14 rituximab-infusion groups, which could suggest that omitting the D14 rituximab remission-maintenance dose did not modify the short-term relapse-free rate. Nevertheless, results at M12 may also have been influenced by the rituximab-infusion strategies for both groups.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antirreumáticos/administração & dosagem , Quimioterapia de Manutenção/métodos , Rituximab/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/sangue , Antígenos CD19 , Intervalo Livre de Doença , Esquema de Medicação , HumanosRESUMO
OBJECTIVES: To investigate the frequency and risk factors of postoperative complications in RA patients treated with tocilizumab (TCZ). METHODS: The French registry REGATE recruited 1496 RA patients receiving TCZ in routine care. Data from patients treated with TCZ who underwent surgery were reviewed. Frequency of post-surgery complications was collected and compared in patients with and without complications in order to identify factors associated with complications. Similar analysis was performed in patients with postoperative infection. RESULTS: We identified 167 patients who underwent 175 surgical procedures including 103 orthopaedic surgeries (58.9%). The patients were mainly women (84%) with a mean disease duration of 14.96±11.29 years. The mean delay between surgery and the last TCZ infusion was 4.94±1.74 weeks. Fifteen patients experienced 15 complications (8.6%) with 10 severe infections including 5 surgical site infections (33.3%). There was no significant difference between patients with and without complications. In multivariate analysis, previous treatment with rituximab in the previous year tended to be associated with postoperative complications (OR: 3.27, IC95% 0.92-11.49, p=0.06). Concerning postoperative infections, diabetes mellitus tended to be associated with this complication (OR: 3.73, IC95% 0.88-15.79, p=0.06) in multivariate analysis. CONCLUSIONS: In RA patients treated with TCZ in perfusion, the rate of surgical complications was low: 8.6%. The median time between surgery and last infusion was relatively short according to half-life of TCZ but did not influence the rate of postoperative complications.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Procedimentos Cirúrgicos Operatórios , Feminino , Humanos , Complicações Pós-Operatórias , Sistema de Registros , Rituximab , Infecção da Ferida CirúrgicaRESUMO
The most common cause of acute renal failure in systemic sclerosis patients is scleroderma renal crisis but other etiologies have to be considered such as another autoimmune disease. We report the case of a 60-year-old male admitted to our hospital with a renal failure. His medical history included a diagnosis of systemic sclerosis 6 months ago. Antinuclear antibodies were positive at a titer of 1:1280 with positive anti-Scl-70 and anti-myeloperoxidase (34 U/mL) antibodies. Scleroderma renal crisis was suspected. However, antineutrophil cytoplasmic antibody-associated vasculitis could not be excluded and a renal biopsy was performed. Histopathology revealed crescentic glomerulonephritis and rupture of Bowman's capsule. Anti-glomerular basement membrane antibodies were detected in serum and the diagnosis of Goodpasture syndrome was confirmed by kidney's immunofluorescence analysis showing typical deposits. Only three other cases of systemic sclerosis associated with Goodpasture syndrome have been reported in the literature. Also, rapidly progressive glomerulonephritis with positivity of both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibodies has been described. Several studies have suggested that antineutrophil cytoplasmic antibody positivity occurs first leading to damages of the glomerular basement membrane, to the release of alpha-3 NC1 antigen, and ultimately to anti-glomerular basement membrane antibody production. Although rare, antineutrophil cytoplasmic antibody-associated vasculitis and Goodpasture syndrome should be searched for in systemic sclerosis patients with acute renal failure.
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OBJECTIVE: To refine the predictive significance of muscle granuloma in patients with myositis. METHODS: A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM). RESULTS: All but 2 patients with granuloma-myositis had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of patients with granuloma-myositis matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining patients with granuloma-myositis did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis. CONCLUSION: Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.
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Granuloma/epidemiologia , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/patologia , Miosite/epidemiologia , Sarcoidose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Comorbidade , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Background: To comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA). Methods: We evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response. Results: Of the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) -0.12 ng/µg (-0.58 to 0.31) vs 0.04 (-0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (-0.05 g/L (-0.11 to -0.01) vs -0.01 g/L (-0.02 to 0.01), p<0.001). When considering the patients' responses to treatment, improved biomarkers were mainly observed in the EULAR responders in each treatment group. Conclusions: TNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA. Trial registration number: ClinicalTrials.gov Identifier NCT01000441, registered on 22 October 2009.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Doenças Cardiovasculares/sangue , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Abatacepte/uso terapêutico , Adiponectina/metabolismo , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Apolipoproteína A-I/efeitos dos fármacos , Apolipoproteína B-100/efeitos dos fármacos , Artrite Reumatoide/complicações , Artrite Reumatoide/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Resistência à Insulina/fisiologia , Leptina/metabolismo , Lipoproteína(a)/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Rituximab/uso terapêuticoRESUMO
OBJECTIVE: To assess the long-term safety, tolerability, and effectiveness of tocilizumab (TCZ) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in clinical practice in patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patients in the 24-week, open-label ACT-SURE study who had at least a moderate EULAR response by week 24 and were from a participating country were eligible for this long-term extension (LTE); the patients continued to receive TCZ 8 mg/kg intravenously every 4 weeks as monotherapy or in combination with ≥ 1 csDMARD for up to an additional 108 weeks. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Effectiveness endpoints included Disease Activity Score in 28 joints (DAS28) responses, American College of Rheumatology (ACR) responses, and patient-reported outcomes (PROs). RESULTS: Of the 1102 patients who completed the core 24-week study, 934 participated in the LTE; the median exposure to TCZ was 64.3 weeks. From baseline to the end of the LTE, AEs and SAEs occurred in 90% and 9% of patients, respectively. The overall event rates (95% CI) of AEs and SAEs were 406.5 per 100 patient-years (PY) (395.5, 417.8) and 8.8 per 100 PY (7.3, 10.6), respectively. Mean (SD) improvement in DAS28 was 4.12 (1.18), P < 0.0001. The DAS28 remission rates, ACR response rates, and PRO scores were maintained during the LTE study. CONCLUSION: In clinical practice, TCZ as monotherapy or in combination with csDMARDs was safe, well tolerated, and efficacious in patients with moderate to severe RA.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM. METHODS: This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model. RESULTS: Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti-TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality. CONCLUSION: Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.