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1.
Medicine (Baltimore) ; 99(2): e18723, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914087

RESUMO

Effectiveness, efficacy and safety of biosimilar infliximab (CT-P13) in inflammatory bowel disease (IBD) patients has been shown in previous studies. Limited data exist on health-related quality of life (HRQoL) of switching originator to biosimilar infliximab (IFX) in IBD patients. The objective of this study was to evaluate impact of switching originator to biosimilar IFX on HRQoL, disease activity, and health care costs in IBD maintenance treatment.In this single-center prospective observational study, all IBD patients receiving maintenance IFX therapy were switched to biosimilar IFX. HRQoL was measured using the generic 15D health-related quality of life instrument (15D) utility measurement and the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ). Crohn Disease Activity Index (CDAI) or Partial Mayo Score (pMayo), and fecal calprotectin (FC) served for evaluation of disease activity. Data were collected at time of switching and 3 and 12 months after switching. Patients' characteristics, clinical background information and costs were collected from patient records and the hospital's electronic database.Fifty-four patients were included in the analysis. No statistically significant changes were observed in 15D, CDAI, pMayo, and FC during 1-year follow-up. IBDQ scores were higher (P = .018) in Crohn disease 3 months after switching than at time of switching. Costs of biosimilar IFX were one-third of costs of originator one. Total costs related to secondary health care (excluding costs of IFX), were similar before and after the onset of biosimilar IFX.HRQoL and disease activity were after switching from originator to biosimilar IFX comparable, but the costs of biosimilar IFX were only one-third of those of the originator one.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Qualidade de Vida , Adulto , Anticorpos Monoclonais/economia , Medicamentos Biossimilares/economia , Substituição de Medicamentos/economia , Feminino , Fármacos Gastrointestinais/economia , Recursos em Saúde/economia , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão
5.
Gastroenterology ; 158(1): 189-199, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600487

RESUMO

BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. METHODS: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P = 5.88 × 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P = 6.60 × 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57-2.58). CONCLUSIONS: In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.


Assuntos
Adalimumab/imunologia , Doença de Crohn/terapia , Cadeias alfa de HLA-DQ/genética , Infliximab/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Alelos , Doença de Crohn/sangue , Feminino , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
12.
S D Med ; 72(10): 454-458, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31816206

RESUMO

Several immunotherapeutic agents function against the T cell immune checkpoint inhibitor pathways thereby reestablishing immune response to elusive malignancies. Namely, the programmed death-1 co-receptor (PD-1) or ligand (PD-L1) and cytotoxic T lymphocyte- associated protein 4 (CTLA-4) are well known checkpoint targets of current FDA approved drugs. Among these drugs nivolumab, an IgG4 anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, are used to treat numerous malignancies but carry a large list of potential side effects termed immune-related adverse effects (irAEs). We describe the presentation, clinical course, and resolution of steroid-resistant immune checkpoint inhibitor-induced colitis secondary to administration of these two drugs in a 66-year-old female patient treated with infliximab.


Assuntos
Anticorpos Monoclonais , Colite , Infliximab/uso terapêutico , Idoso , Anticorpos Monoclonais/uso terapêutico , Colite/induzido quimicamente , Colite/imunologia , Colite/terapia , Feminino , Humanos , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos , Resultado do Tratamento
13.
Clin Exp Rheumatol ; 37 Suppl 121(6): 111-115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856937

RESUMO

OBJECTIVES: The efficacy and safety of biosimilar infliximab (bio-IFX) was shown in randomised controlled trials and it was approved for all indications of the reference product in several countries. However, a previous case series of 3 patients with Behçet's syndrome (BS) reported disappointing results. We aimed to share our experience with bio-IFX treatment in different types of organ involvement in patients with BS. METHODS: We reviewed the charts of all BS patients who were prescribed reference infliximab (ref-IFX) or bio-IFX in our BS clinic. Among the 181 BS patients who were prescribed IFX since 2003, 6 (3%) were prescribed bio-IFX due to refractory disease despite conventional immunosuppressives. RESULTS: A total of 6 patients (mean age: 32.1±6.2, mean disease duration: 5.3±1.8 years, 5 men and 1 woman) received bio-IFX for uveitis, nervous system, vascular and joint involvement. Four of the 6 patients obtained remission and stayed in remission during the 16±6.5 months they used bio-IFX. Among the 4 patients who obtained remission, 2 were switched to ref-IFX due to unavailability of bio-IFX infusion set and did not experience adverse events or loss of efficacy. However, relapses occurred during tapering. The other 2 patients are still in remission with bio- IFX. Among the remaining 2 patients, one had to be switched to ref-IFX after the first infusion, due to a change in the reimbursement policy and the other was non-responsive. CONCLUSIONS: Our limited experience showed that bio-IFX may be a safe and effective alternative for patients with BS, refractory to conventional immunosuppressives.


Assuntos
Síndrome de Behçet , Medicamentos Biossimilares , Infliximab/uso terapêutico , Adulto , Síndrome de Behçet/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Feminino , Humanos , Masculino , Resultado do Tratamento , Uveíte/tratamento farmacológico
14.
Clin Exp Rheumatol ; 37 Suppl 121(6): 137-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856941

RESUMO

OBJECTIVES: Initial recommendations on anti-TNF treatment for Behçet's disease (BD) included an intravenous infliximab infusion for acute posterior uveitis to achieve a fast-onset response. We aimed to examine the long-term outcome of our patients with acute sight-threatening BD who received successful short-term treatment with infliximab. METHODS: We performed a retrospective longitudinal outcome study including consecutive patients who responded to one infliximab infusion (5mg/kg) for BD-associated acute posterior uveitis or panuveitis, followed, or not, by one or two additional infusions. RESULTS: Twelve patients (aged 51±14 years, mean±SD, 67% men) with bilateral (n=9) or unilateral (n=3) ocular attack (relapsing in 9 patients) achieved resolution of ocular inflammation within 4 weeks after the first infusion of infliximab, given as add-on to azathioprine (n=9) or to azathioprine/cyclosporine combination. Ten of 12 patients received a second infusion at 4 weeks and 9 of them received a third infusion at 8 weeks from baseline. Except from a patient who relapsed after 6 months and responded to infliximab re-treatment, 11 patients remain ocular relapse-free during follow-up, ranging from 4 to 16 years (10±4). Five patients (45%) discontinued azathioprine being in full BD remission and remain any drug-free at end of follow-up. CONCLUSIONS: Successful short-term infliximab treatment combined with conventional immunosuppressives for BD-associated sight-threatening uveitis may lead to remission for many years thereafter. This observation may suggest that infliximab as a first-line therapy should be promptly administered to every patient with ocular BD for rapid remission of ocular inflammation and preservation of visual acuity.


Assuntos
Síndrome de Behçet , Infliximab/uso terapêutico , Uveíte , Adulto , Idoso , Anticorpos Monoclonais , Síndrome de Behçet/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/tratamento farmacológico
15.
Acta Cir Bras ; 34(10): e201901004, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851212

RESUMO

PURPOSE: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. METHODS: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. RESULTS: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. CONCLUSION: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.


Assuntos
Colite/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Infliximab/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Fezes , Trânsito Gastrointestinal/efeitos dos fármacos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Peroxidase/análise , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
17.
Harefuah ; 158(11): 752-754, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721521

RESUMO

INTRODUCTION: TNFα antagonists, such as infliximab and adalimumab, are widely used for induction and maintenance of remission in pediatric patients with inflammatory bowel disease (IBD). Numerous studies in adult and pediatric patients have demonstrated that monitoring of anti-TNFα drug level improves various outcomes, especially in cases of primary non-response or loss-of-response. In this article we present the recommendations of the Israeli Pediatric Gastroenterology Association regarding measuring anti-TNFα drug and anti-drug levels in pediatric IBD patients. The recommendation to perform these studies will be provided only by a pediatric gastroenterologist based on clinical, laboratory, endoscopic or radiologic signs of active inflammation. We also recommend performing these studies once a year in patients with clinical and biochemical remission. We believe that implementing these recommendations will improve the care provided for pediatric patients with IBD.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Criança , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pacientes , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Clin Biochem ; 74: 73-75, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669514

RESUMO

BACKGROUND: Infliximab (IFX) is a monoclonal antibody used to treat patients with inflammatory bowel disease (IBD). For IFX therapeutic drug monitoring (TDM), the most commonly used analysis is enzyme-linked immunosorbent assays (ELISA) which do not allow results to be provided in real-time. The aim of this study was to compare the in-house ELISA (Promonitor IFX) with the much faster assay Quantum Blue® IFX (QB) for quantification of serum IFX concentration among IBD patients in maintenance IFX therapy. METHODS: We studied 30 serum samples from outpatients in IFX maintenance therapy at Copenhagen University Hospital Hvidovre, Denmark. Samples were used to compare IFX measurements from Promonitor IFX with QB. Therapeutic intervals of <3 µg/mL, 3-7 µg/mL and >7 µg/mL were equally covered. Differences were evaluated using Bland-Altman plots and Student t-test. Correlation was evaluated using x,y-plot and Pearson's correlation coefficient. The intermediate imprecision (CV%) of QB was measured at two levels (3 µg/mL and 7 µg/mL). For qualitative comparison, weighted kappa statistics (κ) were determined after stratification of results by therapeutic interval. RESULTS: Promonitor IFX and QB were strongly correlated (r = 0.92, p < 0.001). The mean difference between Promonitor IFX and QB was -0.57 µg/mL (p = 0.2). The CV% of QB was 16.3% at 3 µg/mL and 16.7% at 7 µg/mL. Classification of results according to therapeutic interval showed almost perfect agreement (κ = 0.81). CONCLUSIONS: QB is a suitable alternative to Promonitor IFX for TDM in patients treated with IFX for IBD. The results revealed a strong correlation between methods, in particular at lower IFX concentrations, representing the most interesting clinical range. When the samples were stratified according to the therapeutic interval, an almost perfect agreement between the methods was observed.


Assuntos
Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Fármacos Gastrointestinais/sangue , Doenças Inflamatórias Intestinais/sangue , Infliximab/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Dinamarca , Fármacos Gastrointestinais/uso terapêutico , Hospitais Universitários , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pesquisa Qualitativa
20.
Medicine (Baltimore) ; 98(43): e17652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651888

RESUMO

RATIONALE: Intestinal Behçet's disease (BD) is characterized by intestinal ulcerations and gastrointestinal symptoms. Ulcerative intestinal tuberculosis (TB) is usually with dyspepsia, abdominal pain, vomiting, and weight loss. The 2 diseases exhibit similar clinical manifestations, but the most critical aspects of their clinical courses and required treatments are not at all similar. PATIENT CONCERNS: We present a case in which a patient with intestinal Behçet's disease developed a de novo ulcerative intestinal TB infection after the start of anti-tumor necrosis factor-α treatment. This was despite histopathologic examination without caseous necrosis granuloma and negative for acid-fast staining and latent TB screen. DIAGNOSES: Intestinal Behçet's disease and intestinal TB. INTERVENTIONS: The patient was treated with quadruple antituberculous chemotherapy, comprising rifapentine, isoniazid, ethambutol, and pyrazinamide. OUTCOMES: At follow-up about 3 months, the therapy of oral antituberculous drugs and thalidomide was continued and the patient's condition had stabilized. LESSONS: This case illustrates the importance of closely monitoring patients who are on infliximab for possible onset of TB, even without abdominal symptoms, and with negative screening results for latent TB.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/efeitos adversos , Tuberculose Gastrointestinal/induzido quimicamente , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Tuberculose Gastrointestinal/tratamento farmacológico
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