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1.
Yonsei Med J ; 62(2): 177-181, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527798

RESUMO

We sought to analyze the efficacy of adalimumab in active noninfectious uveitis, and evaluate its efficacy and safety for the management of refractory noninfectious uveitis in Korean patients. A retrospective observational study was conducted. A total of 23 eyes of 14 Korean patients with noninfectious uveitis refractory to conventional treatment, including corticosteroid and immunosuppressive agents, were treated with adalimumab between December 2017 and February 2020. The primary outcomes were vitreous haziness grades, anterior chamber cell grades, and central macular thickness measured prior to injection and at 1, 3, 6, and 12 months after the first adalimumab injection. Among the 23 eyes, 14 eyes (60.9%) were diagnosed with panuveitis and 9 eyes (39.1%) with posterior uveitis [mean follow-up period: 22.3 months (7-27)]. The most common etiologic diagnoses requiring adalimumab injection were Behçet's disease (9 eyes, 39.1%), followed by undifferentiated inflammation (6 eyes, 26.1%), Vogt-Koyanagi-Harada disease (3 eyes, 13.0%), psoriasis (2 eyes, 8.7%), serpiginous chorioretinopathy (2 eyes, 8.7%), and systemic lupus erythematosus (1 eye, 4.3%). At the 1-year follow-up after the first injection, anterior chamber cell grade decreased from 0.5±0.4 to 0.3±0.4, and vitreous haziness grade decreased from 1.1±1.1 to 0.3±0.5 (p<0.05). Central macular thickness improved from 347.2±98.1 µm to 264.3±61.1 µm (p<0.05). Adalimumab injection in patients with refractory noninfectious uveitis decreased the anterior chamber cell grade, vitreous haziness grade, and central macular thickness with no severe side effect. Overall, adalimumab injection may, therefore, be an effective and relatively safe treatment modality for noninfectious uveitis in Korean patients.


Assuntos
Adalimumab/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/fisiopatologia , Acuidade Visual/efeitos dos fármacos , Adulto Jovem
3.
PLoS One ; 15(12): e0244620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373425

RESUMO

BACKGROUND: Real-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations. OBJECTIVES: Our aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan. METHODS: We retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan. RESULTS: A total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers. CONCLUSIONS: This real world data showed differential efficacy and safety of the four biological agents.


Assuntos
Adalimumab/administração & dosagem , Etanercepte/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Fatores Biológicos/administração & dosagem , Fatores Biológicos/efeitos adversos , Etanercepte/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Taiwan , Resultado do Tratamento , Ustekinumab/efeitos adversos , Adulto Jovem
4.
Reumatismo ; 72(3): 173-177, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213130

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adalimumab/administração & dosagem , Adulto , Antivirais/administração & dosagem , Artrite Reumatoide/complicações , Azatioprina/administração & dosagem , Terapia Biológica , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Lopinavir/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Oseltamivir/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prednisolona/administração & dosagem , Ritonavir/administração & dosagem
6.
Medicine (Baltimore) ; 99(28): e21131, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664142

RESUMO

INTRODUCTION: Tumor necrosis factor alpha (TNF-α) mediated inflammation has been implicated, in knee osteoarthritis, despite being a predominantly degenerative condition. PATIENT CONCERNS: A 56-year old female, a case of left knee pain not responding to conventional conservative strategies. DIAGNOSIS: A diagnosis of primary osteoarthritis of the left knee, grade 3 osteoarthritis as per the Kellgren-Lawrence Scale was established. INTERVENTIONS: She was administered an intra-articular injection of 10 mg of Adalimumab, a commonly used anti-TNF agent. OUTCOMES: The patient was evaluated at baseline, 1 month, 3 months, and at 6 months. There was a marked improvement in pain intensity (visual analog scale) and quality of life, despite no objective change on the parameters seen on ultrasound of the knee. CONCLUSION: Injection of adalimumab via the intra-articular route into the knee joint in primary osteoarthritis yields promising results.


Assuntos
Adalimumab/administração & dosagem , Artralgia/diagnóstico , Osteoartrite do Joelho/tratamento farmacológico , Medição da Dor/métodos , Antirreumáticos/administração & dosagem , Artralgia/tratamento farmacológico , Artralgia/etiologia , Feminino , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Medicine (Baltimore) ; 99(19): e20201, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384515

RESUMO

Most studies of methotrexate (MTX) in combination with tumor necrosis factor (TNF) inhibitors have focused on treatment-naive patients with early disease. The goal of this study was to evaluate whether previous biologic therapy influenced the impact of concomitant MTX in patients initiating treatment with adalimumab.We retrospectively analyzed data from 2 large noninterventional studies of German patients with active rheumatoid arthritis (RA) who initiated adalimumab therapy during routine clinical practice. Patients were seen between April 2004 and February 2013 for study 1 and between April 2003 and March 2013 for study 2. Key outcomes were Disease Activity Score-28 joints (DAS28), patient global assessment of health (PGA), and pain. Subgroup analyses by prior biologic treatment were performed on patients treated with continuous adalimumab monotherapy or adalimumab plus MTX for 12 months and 2-sample t tests were used to evaluate differences. We also assessed outcomes in subgroups in which MTX had been added or removed at 6 months and compared outcomes with 1-sample t tests.Of 2654 patients, 1911 (72%) were biologic naive and 743 (28%) had received prior biologic therapy, usually with a TNF inhibitor. All subgroups showed improvements following initiation of adalimumab therapy. In patients with no previous biologic treatment, continuous adalimumab plus MTX was associated with greater improvements in DAS28, PGA, and pain at month 12 compared with continuous adalimumab monotherapy (P = .0006, .0031, and .0032, respectively). In patients with previous biologic treatment, concomitant MTX was associated with statistically significant benefits in pain only. Adding MTX at month 6 resulted in additional benefits in patients with no prior biologic therapy, but not those with previous biologics.We conclude that concomitant MTX resulted in additional improvements in DAS28 and PGA vs adalimumab monotherapy in patients with no previous biologic therapy, but changes were not statistically significant in patients treated with prior biologics. These findings may help inform the patient/provider treatment decision during routine clinical care.


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Adalimumab/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/complicações , Produtos Biológicos , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Nível de Saúde , Humanos , Masculino , Metotrexato/administração & dosagem , Dor/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
Lancet ; 395(10235): 1496-1505, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386593

RESUMO

BACKGROUND: Head-to-head trials in psoriatic arthritis are helpful in guiding clinical decision making. The EXCEED study evaluated the efficacy and safety of secukinumab versus adalimumab as first-line biological monotherapy for 52 weeks in patients with active psoriatic arthritis, with a musculoskeletal primary endpoint of American College of Rheumatology (ACR) 20 response. METHODS: This parallel-group, double-blind, active-controlled, phase-3b, multicentre (168 sites in 26 countries) trial enrolled patients aged at least 18 years with active psoriatic arthritis. Eligible patients were randomly assigned (1:1) by means of interactive response technology to receive secukinumab or adalimumab. Patients, investigators, site personnel, and those doing the assessments (except independent study drug administrators) were masked to study assignment. 300 mg secukinumab was administered subcutaneously at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 48 as a pre-filled syringe. Adalimumab was administered every 2 weeks from baseline until week 50 as 40 mg per 0·4 mL citrate free subcutaneous injection. The primary outcome was the proportion of patients with at least 20% improvement in the ACR response criteria (ACR20) at week 52. Patients were analysed according to the treatment to which they were randomly assigned. Safety analyses included all safety data reported up to and including the week 52 visit for each patient who received at least one dose of study drug. The trial is registered at ClinicalTrials.gov, NCT02745080. FINDINGS: Between April 3, 2017 and Aug 23, 2018, we randomly assigned 853 patients to receive secukinumab (n=426) or adalimumab (n=427). 709 (83%) of 853 patients completed week 52 of the study, of whom 691 (81%) received the last study treatment at week 50. 61 (14%) of 426 patients in the secukinumab group discontinued treatment by week 52 versus 101 (24%) of 427 patients in the adalimumab group. The primary endpoint of superiority of secukinumab versus adalimumab for ACR20 response at week 52 was not met. 67% of patients in the secukinumab group achieved an ACR20 response at week 52 versus 62% of patients in the adalimumab group (OR 1·30, 95% CI 0·98-1·72; p=0·0719). The safety profiles of secukinumab and adalimumab were consistent with previous reports. Seven (2%) of 426 patients in the secukinumab group and six (1%) of 427 patients in the adalimumab group had serious infections. One death was reported in the secukinumab group due to colon cancer and was assessed as not related to the study drug by the investigator. INTERPRETATION: Secukinumab did not meet statistical significance for superiority versus adalimumab in the primary endpoint of ACR20 response at week 52. However, secukinumab was associated with a higher treatment retention rate than adalimumab. This study provides comparative data on two biological agents with different mechanisms of action, which could help guide clinical decision making in the management of patients with psoriatic arthritis. FUNDING: Novartis Pharma.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Tomada de Decisão Clínica , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Segurança , Resultado do Tratamento
10.
Aliment Pharmacol Ther ; 51(12): 1342-1352, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32379358

RESUMO

BACKGROUND: Virtual clinics represent a novel model of care in inflammatory bowel disease. Their effectiveness in promoting high quality use of biologic therapy and facilitating a treat-to-target approach is unknown. AIM: To evaluate clinical and process-driven outcomes in a virtual clinic compared to standard outpatient care amongst patients receiving intensified anti-TNF therapy for secondary loss of response. METHODS: We performed a retrospective multi-centre, parallel, observational cohort study of Crohn's disease patients receiving intensified anti-TNF therapy for secondary loss of response. Objective assessments of disease activity and anti-TNF trough levels at secondary loss of response and during subsequent 6-month semesters, were compared longitudinally between virtual clinic and standard outpatient care cohorts. The primary endpoint was treatment success, with appropriateness of dose intensification, tight disease monitoring and treatment de-escalation representing secondary outcomes. RESULTS: Of 149 patients with similar baseline characteristics, 69 were managed via a virtual clinic and 80 via standard outpatient care. There were higher rates of treatment success in the virtual clinic cohort (60.9 vs 35.0%, P < 0.002). Rates of appropriate dose intensification (82.6% vs 40.0%, P < 0.001), biomarker remission (faecal calprotectin P = 0.002), tight-disease monitoring (84.1% vs 28.8%, P < 0.001) and treatment de-escalation (21.3% vs 10.0%, P = 0.027) also favoured the virtual clinic cohort. CONCLUSION: This study favoured a virtual clinic-led model-of-care over standard outpatient care in facilitating treatment success as part of an effective treat-to-target approach in Crohn's disease. A virtual clinic model-of-care also improved treatment outcomes and quality of use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and tight-disease monitoring, while encouraging more frequent dose de-escalation.


Assuntos
Assistência Ambulatorial/métodos , Produtos Biológicos/administração & dosagem , Doença de Crohn/tratamento farmacológico , Planejamento de Assistência ao Paciente , Medicina de Precisão/métodos , Telemedicina/métodos , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/normas , Produtos Biológicos/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente/normas , Medicina de Precisão/normas , Estudos Retrospectivos , Índice de Gravidade de Doença , Padrão de Cuidado , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
11.
Ann Rheum Dis ; 79(8): 1023-1030, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32404343

RESUMO

OBJECTIVE: To investigate the association between baseline disease activity and the occurrence of flares after adalimumab tapering or withdrawal in patients with rheumatoid arthritis (RA) in sustained remission. METHODS: The PREDICTRA phase IV, randomised, double-blind (DB) study (ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels, and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Patients) enrolled patients with RA receiving adalimumab 40 mg every other week who were in sustained remission ≥6 months. After a 4-week, open-label lead-in (OL-LI) period, patients were randomised 5:1 to DB adalimumab taper (every 3 weeks) or withdrawal (placebo) for 36 weeks. The primary endpoint was the association between DB baseline hand and wrist MRI-detected inflammation with flare occurrence. RESULTS: Of 146 patients treated during the OL-LI period, 122 were randomised to taper (n=102) or withdrawal (n=20) arms. Patients had a mean 12.9 years of active disease and had received adalimumab for a mean of 5.4 years (mean 2.2 years in sustained remission). Overall, 37 (36%) and 9 (45%) patients experienced a flare in the taper and withdrawal arms, respectively (time to flare, 18.0 and 13.3 weeks). None of the DB baseline disease characteristics or adalimumab concentration was associated with flare occurrence after adalimumab tapering. Approximately half of the patients who flared regained clinical remission after 16 weeks of open-label rescue adalimumab. The safety profile was consistent with previous studies. CONCLUSIONS: Approximately one-third of patients who tapered adalimumab versus half who withdrew adalimumab experienced a flare within 36 weeks. Time to flare was numerically longer in the taper versus withdrawal arm. Baseline MRI inflammation was not associated with flare occurrence. TRIAL REGISTRATION NUMBER: NCT02198651, EudraCT 2014-001114-26.


Assuntos
Adalimumab/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Exacerbação dos Sintomas , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão
12.
Acta Cir Bras ; 35(2): e202000202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267288

RESUMO

PURPOSE: To investigate the effects of adalimumab pretreatment on the lipopolysaccharide-mediated myocardial injury. METHODS: Twenty-eight Wistar rats were randomized into four groups (n=7). Control (C) group animals were injected once a day with intraperitoneal (i.p) 0.9 % saline for two days. In the Adalimumab (Ada) group, adalimumab was injected at a dose of 10 mg/kg/ day (i.p) for two days. Lipopolysaccharide (Lps) group rats were injected with a dose of 5 mg/kg (i.p) lipopolysaccharide. Lipopolysaccharide + Adalimumab (Lps+Ada) group rats received adalimumab before the administration of lipopolysaccharide. The animals were sacrificed 24 h after the last injection and blood samples were obtained for determination of biochemical cardiac injury markers and circulating levels of TNF-α and interleukin-6 (IL-6). Hearts were harvested for histological examination. RESULTS: Endotoxin exposure resulted in significant increases in serum cardiac injury markers, serum cytokines and histological myocardial injury scores in the Lps group. The levels of circulating cytokines, cardiac injury markers and histological injury scores for myocardial necrosis, perivascular cell infiltration, and inflammation were significantly reduced in Lps+Ada as compared to Lps group (p<0.05). CONCLUSIONS: Adalimumab pretreatment reduces endotoxin-induced myocardial damage in rats. This beneficial effect is thought to be related to the reduction of cytokine release.


Assuntos
Adalimumab/administração & dosagem , Cardiopatias/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Endotoxinas , Feminino , Cardiopatias/induzido quimicamente , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossíntese
13.
Aliment Pharmacol Ther ; 51(11): 1031-1038, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32329532

RESUMO

BACKGROUND: Biologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates. After multiple failed therapies, combining two biologic therapies is possibly the sole medical alternative to recurrent surgery. However, data on this approach are limited. AIMS: To assess the efficacy and safety of concomitant use of two biologic therapies in the largest cohort to date of refractory Crohn's disease patients. METHODS: Data were extracted from Crohn's disease patients started on dual biologic therapy at two referral centres. Biologics utilised include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab. The primary outcome was endoscopic improvement (>50% reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated). Endoscopic remission (SES-CD < 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 < 8), and C-reactive protein (CRP) were also assessed. RESULTS: A total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified. The majority of patients had prior surgical resections (91%), stricturing (59%) or penetrating (36%) phenotype, and perianal fistulas (50%). Median number of prior failed biologics was 4. Endoscopic improvement occurred in 43% of trials and 26% achieved endoscopic remission. Fifty per cent had clinical response and 41% achieved clinical remission. There were significant post-treatment reductions in median SES-CD (14.0 [12.0-17.5] to 6.0 [2.5-8.0], P = 0.0005], PRO-2 (24.1 [20.3-27.0] to 13.4 [4.6-21.8], P = 0.002] and CRP (17.0 [11.0-24.0] to 9.0 [4.0-14.0], P = 0.02). Presence of perianal fistulas decreased from 50% to 33%. Adverse events occurred in 13% of trials. CONCLUSION: Dual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics. Further studies are needed to validate this approach.


Assuntos
Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Doença de Crohn/tratamento farmacológico , Resistência a Medicamentos , Quimioterapia Combinada , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Certolizumab Pegol/administração & dosagem , Certolizumab Pegol/efeitos adversos , Estudos de Coortes , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/metabolismo , Resistência a Medicamentos/efeitos dos fármacos , Quimioterapia Combinada/efeitos adversos , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos , Adulto Jovem
14.
Cochrane Database Syst Rev ; 4: CD012005, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32297974

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and ulcerative colitis are the two main types. Fatigue is a common, debilitating and burdensome symptom experienced by individuals with IBD. The subjective, complex nature of fatigue can often hamper its management. The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies. OBJECTIVES: To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment, placebo or active comparator. SEARCH METHODS: A systematic search of the databases Embase, MEDLINE, Cochrane Library, CINAHL, PsycINFO was undertaken from inception to July 2018. A top-up search was run in October 2019. We also searched the Cochrane IBD Group Specialized Register, the Cochrane Central Register of Controlled Trials, ongoing trials and research registers, conference abstracts and reference lists for potentially eligible studies. SELECTION CRITERIA: Randomised controlled trials of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome using a generic or disease-specific fatigue measure, a subscale of a larger quality of life scale or as a single-item measure, were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results and four authors extracted and assessed bias independently using the Cochrane 'Risk of bias' tool. The primary outcome was fatigue and the secondary outcomes included quality of life, adverse events (AEs), serious AEs and withdrawal due to AEs. Standard methodological procedures were used. MAIN RESULTS: We included 14 studies (3741 participants): nine trials of pharmacological interventions and five trials of non-pharmacological interventions. Thirty ongoing studies were identified, and five studies are awaiting classification. Data on fatigue were available from nine trials (1344 participants). In only four trials was managing fatigue the primary intention of the intervention (electroacupuncture, physical activity advice, cognitive behavioural therapy and solution-focused therapy). Electroacupuncture Fatigue was measured with Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (scores range from 0 to 52). The FACIT-F score at week eight was 8.00 points higher (better) in participants receiving electroacupuncture compared with no treatment (mean difference (MD) 8.00, 95% CI 6.45 to 9.55; 1 RCT; 27 participants; low-certainty evidence). Results at week 16 could not be calculated. FACIT-F scores were also higher with electroacupuncture compared to sham electroacupuncture at week eight (MD 5.10, 95% CI 3.49 to 6.71; 1 RCT; 30 participants; low-certainty evidence) but not at week 16 (MD 2.60, 95% CI 0.74 to 4.46; 1 RCT; 30 participants; low-certainty evidence). No adverse events were reported, except for one adverse event in the sham electroacupuncture group. Cognitive behavioural therapy (CBT) and solution-focused therapy Compared with a fatigue information leaflet, the effects of CBT on fatigue are very uncertain (Inflammatory Bowel Disease-Fatigue (IBD-F) section I: MD -2.16, 95% CI -6.13 to 1.81; IBD-F section II: MD -21.62, 95% CI -45.02 to 1.78; 1 RCT, 18 participants, very low-certainty evidence). The efficacy of solution-focused therapy on fatigue is also very uncertain, because standard summary data were not reported (1 RCT, 98 participants). Physical activity advice One 2 x 2 factorial trial (45 participants) found physical activity advice may reduce fatigue but the evidence is very uncertain. At week 12, compared to a control group receiving no physical activity advice plus omega 3 capsules, FACIT-F scores were higher (better) in the physical activity advice plus omega 3 group (FACIT-F MD 6.40, 95% CI -1.80 to 14.60, very low-certainty evidence) and the physical activity advice plus placebo group (FACIT-F MD 9.00, 95% CI 1.64 to 16.36, very low-certainty evidence). Adverse events were predominantly gastrointestinal and similar across physical activity groups, although more adverse events were reported in the no physical activity advice plus omega 3 group. Pharmacological interventions Compared with placebo, adalimumab 40 mg, administered every other week ('eow') (only for those known to respond to adalimumab induction therapy), may reduce fatigue in patients with moderately-to-severely active Crohn's disease, but the evidence is very uncertain (FACIT-F MD 4.30, 95% CI 1.75 to 6.85; very low-certainty evidence). The adalimumab 40 mg eow group was less likely to experience serious adverse events (OR 0.56, 95% CI 0.33 to 0.96; 521 participants; moderate-certainty evidence) and withdrawal due to adverse events (OR 0.48, 95%CI 0.26 to 0.87; 521 participants; moderate-certainty evidence). Ferric maltol may result in a slight increase in fatigue, with better SF-36 vitality scores reported in the placebo group compared to the treatment group following 12 weeks of treatment (MD -9.31, 95% CI -17.15 to -1.47; 118 participants; low-certainty evidence). There may be little or no difference in adverse events (OR 0.55, 95% CI 0.26 to 1.18; 120 participants; low-certainty evidence) AUTHORS' CONCLUSIONS: The effects of interventions for the management of fatigue in IBD are uncertain. No firm conclusions regarding the efficacy and safety of interventions can be drawn. Further high-quality studies, with a larger number of participants, are required to assess the potential benefits and harms of therapies. Future studies should assess interventions specifically designed for fatigue management, targeted at selected IBD populations, and measure fatigue as the primary outcome.


Assuntos
Fadiga/terapia , Doenças Inflamatórias Intestinais/complicações , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Terapia Cognitivo-Comportamental , Eletroacupuntura , Exercício Físico , Fadiga/etiologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/efeitos adversos , Compostos Férricos/efeitos adversos , Hematínicos/efeitos adversos , Humanos , Psicoterapia Breve , Pironas/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Arch Virol ; 165(5): 1197-1206, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32236683

RESUMO

Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.


Assuntos
Adalimumab/administração & dosagem , Peritonite Infecciosa Felina/terapia , Fatores Imunológicos/administração & dosagem , Itraconazol/administração & dosagem , Animais , Gatos , Quimioterapia Combinada/métodos , Peritonite Infecciosa Felina/patologia , Imunoterapia/métodos , Resultado do Tratamento
16.
Pharmacol Rep ; 72(2): 389-399, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124389

RESUMO

BACKGROUND: Psoriasis is a multifactorial autoimmune disease, which underlies the abnormalities of the apoptotic process. In cases of psoriasis and psoriatic arthritis, biological treatment is used. This study aimed to determine any changes in the expression of the genes associated with apoptosis in patients with psoriatic arthritis treated with adalimumab and to assess any phenotypic modifications based on changes in dermatological indexes. METHODS: The study included 20 patients with psoriatic arthritis treated biologically and 20 healthy volunteers. The research material consisted of peripheral blood mononuclear cells (PBMCs) from which the total RNA was isolated. Changes in the gene expression were determined using oligonucleotide microarrays and RT-qPCR. The clinical condition was assessed based on selected indicators: PASI, BSA [%], DAS28, and DLQI, which were determined every 3 months. RESULTS: There were changes in the expression of genes associated with apoptosis. Significant differences were found for ROCK1, RhoA, and LIMK2 expression profiles in PBMCs. At the initial stage of treatment, a decrease in the PASI and BSA rates was observed. At the later stages, the values of these indicators increased once again. There were correlations between the changes in these genes' expression and the dermatological markers. CONCLUSION: Adalimumab influences the expression of genes related to apoptosis and the values of dermatological indicators of patients. Changes in the expression level of genes associated with apoptosis suggest that ROCK1, RhoA, and LIMK2 may be genes that can potentially be indicators of treatment effectiveness and lack of response to biological treatment.


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Apoptose/efeitos dos fármacos , Artrite Psoriásica/tratamento farmacológico , Quinases Lim/genética , Quinases Associadas a rho/genética , Proteína rhoA de Ligação ao GTP/genética , Adalimumab/administração & dosagem , Antirreumáticos/administração & dosagem , Apoptose/genética , Artrite Psoriásica/sangue , Artrite Psoriásica/genética , Estudos de Casos e Controles , Voluntários Saudáveis , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , RNA Mensageiro/genética , Resultado do Tratamento
17.
BMJ Case Rep ; 13(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32139450

RESUMO

We report the case of a 63-year-old male patient admitted to our emergency department for dyspnoea, peripheral oedema, severe diarrhoea and asthenia. History revealed Crohn's disease (CD) submitted to several intestinal surgical resections in the previous years. He recently started a treatment with adalimumab for the control of CD. Laboratory tests at the admission revealed severe haemolytic anaemia and thrombocytopaenia. Haptoglobin levels were low, schistocyte count was markedly increased. In the suspect of thrombotic microangiopathy, he was admitted to our internal medicine department where we urgently started plasma exchange (PEX). We observed normal ADAMTS-13 activity in absence of Shiga toxin or enterotoxic Escherichia c oli at stool tests. Despite a diagnosis of atypical haemolytic-uraemic syndrome, we observed full platelet count recovery and schistocytes normalisation after the fourth PEX. We then put a diagnosis of adalimumab-induced thrombocytopaenic microangiopathy. Adalimumab was withdrawn. We did not observe relapses in the following 3 months.


Assuntos
Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Microangiopatias Trombóticas/induzido quimicamente , Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Doença de Crohn/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade
18.
Aliment Pharmacol Ther ; 51(9): 852-860, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32201971

RESUMO

BACKGROUND: Few data exist to help select a second biologic agent in patients with refractory ulcerative colitis (UC). AIM: To compare the efficacy of infliximab (IFX) and vedolizumab (VDZ) in UC patients who failed a first subcutaneous anti-tumor necrosing factor (TNF) agent. METHODS: Consecutive UC patients from 12 French centres starting IFX or VDZ after at least one injection of adalimumab or golimumab have been included in a retrospective study. Outcomes were clinical remission at week 14, survival without treatment discontinuation and survival without UC-related event. RESULTS: Among the 225 patients included, clinical remission at week 14 was achieved in 40/154 (26%) patients treated with IFX and in 35/71 (49%) treated with VDZ (P = 0.001). After a propensity score matching analysis, this difference remained significant (odds ratio: 1.67; 95% confidence interval: 1.08-2.56; P = 0.02). With a median follow-up of 117 weeks, survival rates without treatment discontinuation at years 1 and 3 were 50% and 29% with IFX, and 80% and 55% with VDZ, respectively (P < 0.001). Regarding survival without UC-related event, they were 49% and 27% with IFX, and 74% and 52% with VDZ (P < 0.01). CONCLUSION: After failure of a first subcutaneous anti-TNF agent, UC patients were more likely to achieve clinical remission with VDZ than those treated with IFX. Although due to prescription habits patients in the IFX group had a significantly more severe disease, these differences remained after adjustments and subgroup analyses. Such results have to be confirmed prospectively and warrant dedicated head-to-head trials.


Assuntos
Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Fatores Biológicos/administração & dosagem , Fatores Biológicos/efeitos adversos , Estudos de Coortes , Colite Ulcerativa/patologia , Pesquisa Comparativa da Efetividade , Substituição de Medicamentos , Feminino , Humanos , Infliximab/efeitos adversos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
19.
Medicine (Baltimore) ; 99(10): e18925, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150045

RESUMO

There is little consensus on the optimal timing of anti-tumor necrosis factor (anti-TNF) therapy to decrease the rates of hospitalization and surgery in Crohn disease (CD). We aimed to assess the real-world outcomes of anti-TNF therapy and estimate the optimal timing of anti-TNF therapy in Korean patients with CD.Claims data were extracted from the Korean Health Insurance Review and Assessment Service database. Incident patients diagnosed with CD between 2009 and 2016, with at least 1 anti-TNF drug prescription, and with follow-up duration > 6 months were stratified according to the number of relapses prior to initiation of anti-TNF therapy: groups A (≤1 relapse), B (2 relapses), C (3 relapses), and D (≥4 relapses). The cumulative survival curves free from emergency hospitalization (EH) and surgery were compared across groups.Among the 2173 patients analyzed, the best and worst prognoses were noted in groups A and D, respectively. The incidences of EH and surgery decreased significantly as the use of anti-TNF agents increased. The 5-year rate of hospitalization was significantly lower in group A than in groups C and D (P = .004 and .020, respectively), but similar between groups A and B. The 5-year rate of surgery was lower in group A than in group C (P = .024), but similar among groups A, B, and D.In Asian patients with CD, anti-TNF therapy reduces the risk of EH and surgery and should be considered before three relapses, regardless of disease duration.


Assuntos
Doença de Crohn/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Administração Oral , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Incidência , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Revisão da Utilização de Seguros , Masculino , Recidiva , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
20.
Drugs Aging ; 37(5): 383-392, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32016824

RESUMO

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. RESULTS: We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60-80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18-59 years; 57 males). Older patients with Crohn's disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. CONCLUSION: Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento/estatística & dados numéricos , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
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