RESUMO
PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.
Assuntos
Inibidores da Angiogênese , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Acuidade Visual , Degeneração Macular Exsudativa , Humanos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Tomografia de Coerência Óptica/métodos , Idoso , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia , Inibidores da Angiogênese/administração & dosagem , Idoso de 80 Anos ou mais , Substituição de Medicamentos/métodos , Resultado do Tratamento , Seguimentos , Angiofluoresceinografia/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fundo de OlhoRESUMO
PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.
Assuntos
Inibidores da Angiogênese , Retinopatia Diabética , Injeções Intravítreas , Edema Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Edema Macular/tratamento farmacológico , Edema Macular/diagnóstico , Edema Macular/etiologia , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Pessoa de Meia-Idade , Inibidores da Angiogênese/administração & dosagem , Tomografia de Coerência Óptica/métodos , Seguimentos , Idoso , Resultado do Tratamento , Substituição de Medicamentos/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
CASE PRESENTATION: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years.
Assuntos
COVID-19/diagnóstico , Substituição de Medicamentos/métodos , Lacosamida/administração & dosagem , Doenças Pulmonares Intersticiais , Pulmão , Fenitoína , Convulsões/tratamento farmacológico , Biópsia/métodos , COVID-19/epidemiologia , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Pessoa de Meia-Idade , Fenitoína/administração & dosagem , Fenitoína/efeitos adversos , SARS-CoV-2 , Convulsões/complicações , Convulsões/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversosRESUMO
BACKGROUND: Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma. METHODS: Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained. RESULTS: Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein-Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively. CONCLUSIONS: This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Colite Ulcerativa , Doença de Crohn , Substituição de Medicamentos/métodos , Infliximab , Linfoma , Adolescente , Idade de Início , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfoma/diagnóstico , Linfoma/etiologia , Linfoma/fisiopatologia , Linfoma/terapia , Masculino , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity. AIMS: We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival. METHODS: We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient. RESULTS: Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase. CONCLUSIONS: Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities.
Assuntos
Azatioprina , Colite Ulcerativa , Doença de Crohn , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Mercaptopurina/análogos & derivados , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Antimetabólitos/administração & dosagem , Antimetabólitos/efeitos adversos , Antimetabólitos/farmacocinética , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Azatioprina/farmacocinética , Biomarcadores Farmacológicos/sangue , Criança , Estudos de Coortes , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Substituição de Medicamentos/métodos , Substituição de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Nucleotídeos de Guanina/sangue , Humanos , Masculino , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Mercaptopurina/farmacocinética , Países Baixos/epidemiologia , Estudos Retrospectivos , Tionucleotídeos/sangueAssuntos
Substituição de Medicamentos/métodos , Fatores Imunológicos/administração & dosagem , Leucoencefalopatia Multifocal Progressiva/prevenção & controle , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Natalizumab/efeitos adversos , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/imunologia , Esclerose Múltipla/imunologia , Estudos Observacionais como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Clozapine is an effective drug for the management of schizophrenia that has not responded to other agents, but some patients experience insufficient or adverse effects and discontinue treatment. OBJECTIVE: We investigated a potential association between clozapine serum concentrations and switching to other antipsychotics in a large real-world patient population from a therapeutic drug monitoring service. METHODS: Absolute and dose-adjusted serum concentrations (concentration-to-dose ratios [C/D ratios]) of clozapine during dosing between 100 and 1000 mg/day were measured in 1979 Norwegian patients during the period 2005-2019. These variables were compared in patients switching to other antipsychotic drugs versus maintaining clozapine treatment using linear mixed models. Smoking habits were known for 49% of the patients. To prevent potential nonadherence affecting clozapine switching, only patients with serum concentrations above 50% of the lower reference range were included. RESULTS: In total, 190 patients (9.6%) switched from clozapine to another antipsychotic drug during the study period, whereas the remaining patients were not detected as switchers and were interpreted as maintaining treatment. Patients switching treatment had 23.5% lower absolute concentrations (954 vs. 1245 nmol/L; p < 0.001) and 15.7% lower daily doses (305 vs. 362 mg/day; p < 0.001) of clozapine than did nonswitchers, making the clozapine C/D ratio 9.7% lower in switchers than in nonswitchers after correcting for smoking habits (2.80 vs. 3.10 nmol/L/mg/day; p = 0.032). CONCLUSIONS: The present study suggests that decreased absolute and dose-adjusted serum concentrations of clozapine were associated with clozapine discontinuation. The significantly reduced clozapine concentrations regardless of prescribed dose in switchers versus nonswitchers may indicate a pharmacokinetic mechanism underlying the risk of clozapine discontinuation.
Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Substituição de Medicamentos/métodos , Quimioterapia de Manutenção/métodos , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Noruega/epidemiologia , Estudos Retrospectivos , Esquizofrenia/epidemiologiaRESUMO
OBJECTIVE: To assess the efficacy of golimumab (GLM) as a treatment option for juvenile idiopathic arthritis (JIA)-associated uveitis refractory to adalimumab (ADA). METHODS: Retrospective single-centre study including patients with JIA receiving GLM for active uveitis after failing ADA. JIA- and uveitis-related data, including intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications were evaluated at start of GLM treatment, at 1 month and 3 months, and every 3 months thereafter during GLM administration. We further investigated the association of response to GLM with primary and secondary failure of ADA treatment. RESULTS: Ten patients were studied, all female (17 affected eyes, mean age 14.3 + 6.7 yrs., mean follow-up 25.2 + 21.7 mos). Two patients were switched to GLM because of primary non-response to ADA. Eight were switched because of loss of response (LOR). In 5 of the latter LOR was associated with neutralizing anti-ADA-antibodies. Response to GLM was observed in all 8 patients with LOR, while the 2 patients with primary non-response to ADA also did not respond to GLM. Three of the 8 responders experienced LOR. At the end of follow-up 4 of the 5 remaining responders had achieved complete response. One had achieved partial response. CONCLUSION: GLM is an efficacious therapeutic option in patients who experience LOR to ADA. Our data indicate that patients without primary response to ADA should be rather switched to a biologic agent with a different mode of action instead of further blocking the TNF-alpha pathway.
Assuntos
Adalimumab , Anticorpos Monoclonais/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Substituição de Medicamentos/métodos , Uveíte , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adolescente , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Artrite Juvenil/imunologia , Áustria/epidemiologia , Produtos Biológicos/administração & dosagem , Biomarcadores Farmacológicos , Criança , Monitoramento de Medicamentos/métodos , Duração da Terapia , Feminino , Humanos , Testes Imunológicos/métodos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
OBJECTIVE: To evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF). METHODS: We conducted a cohort study using US Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects. RESULTS: 51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (-1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI. CONCLUSION: ARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.
Assuntos
Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca Sistólica , Neprilisina/antagonistas & inibidores , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Progressão da Doença , Substituição de Medicamentos/métodos , Substituição de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada/métodos , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Insuficiência Cardíaca Sistólica/diagnóstico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca Sistólica/epidemiologia , Insuficiência Cardíaca Sistólica/metabolismo , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Medicare/estatística & dados numéricos , Conduta do Tratamento Medicamentoso/normas , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Mortalidade , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
ABSTRACT: During the last years there has been an increasing availability of drugs (biologics and small molecules) with different mechanisms of action (MoA) in psoriatic arthritis (PsA). New issues about treatment strategies have arisen. The main aim of this study is to verify if there is a difference in terms of clinical efficacy (i.e. retention rate) between cycling (i.e. treating patients with the same MoA after the failure of the previous one) or swap (i.e choosing drugs with a MoA different from the failed previous one) strategies in PsA.In this mono-centric medical records review study, PsA patients treated with biologics, apremilast or tofacitinib were enrolled. Every prescription was clustered in three groups: cycling (CG), swap (SG) or first line group (1LG). Kaplan-Meier analysis and Cox test estimated and compared drugs' retention rate in CG, SG and 1LG. Pâ<â.05 was considered statistically significant.One hundred eighty-three PsA patients were enrolled (9967 patient-months). In CG and 1LG the more prescribed drugs were tumor necrosis factor inhibitor (respectively 99% and 89%), in SG interleukin 17 inhibitor (60%). There were no differences in terms of sex, age, disease duration, and retention rate between CG and SG. The 18-months retention rate of 1LG, SG and CG was 77%, 60%, and 51% respectively. The CG retention rate was lower than in 1LG (Pâ=â.03).The findings of this study suggest that in PsA the swap strategy gives no remarkable advantage compared to cycling. However, patients undergoing swap strategy may experience the same failure rate observed in naives.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Substituição de Medicamentos/métodos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Análise por Conglomerados , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do TratamentoRESUMO
The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing-remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR 0.485, CI 95% 0.264-0.893, p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR 0.248 CI 95% 0.065-0.948, p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Assuntos
Substituição de Medicamentos/métodos , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Cladribina/administração & dosagem , Substituição de Medicamentos/tendências , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/epidemiologia , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Natalizumab/administração & dosagem , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Rituximab/administração & dosagem , Adulto JovemAssuntos
Monofosfato de Adenosina/análogos & derivados , Oclusão Coronária , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Dispneia , Infarto Miocárdico de Parede Inferior , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST , Ticagrelor , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Idoso , Ansiedade/etiologia , Ansiedade/terapia , Dor no Peito/diagnóstico , Angiografia Coronária/métodos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/tratamento farmacológico , Oclusão Coronária/cirurgia , Substituição de Medicamentos/métodos , Stents Farmacológicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Dispneia/etiologia , Dispneia/fisiopatologia , Dispneia/terapia , Eletrocardiografia/métodos , Humanos , Infarto Miocárdico de Parede Inferior/diagnóstico , Infarto Miocárdico de Parede Inferior/fisiopatologia , Infarto Miocárdico de Parede Inferior/terapia , Masculino , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
PURPOSE: To compare outcomes of a treatment algorithm that allows for switching treatment-resistant neovascular age-related macular degeneration (nAMD) eyes to aflibercept with continuing bevacizumab. METHODS: Retrospective study of nAMD patients who initiated treatment in 2012 (aflibercept unavailable) and 2018 (aflibercept available). Eyes were included in the case of residual macular fluid after a minimum of 4 monthly bevacizumab injections. Only eyes in the 2018 group could then switch to aflibercept. RESULTS: The study included 40 eyes from 2012 and 88 eyes from 2018. Patient characteristics were similar across the groups at baseline and 4 months. In 2018, 59 eyes (67%) were switched to aflibercept after 4 months. Mean change in BCVA from 4 months to one year was +2.8 letters in 2018 versus -1.7 letters in 2012 (p = 0.043). Mean change in BCVA from baseline to one year was +9.4 letters in 2018 (p < 0.001) and +4.4 letters in 2012 (p = 0.073). Mean change in CRT from 4 months to one year was -36 µm in 2018 versus -23 µm in 2012 (p = 0.373). Mean change in CRT from baseline to one year was -100 µm in 2018 (p < 0.001) and -75 µm in 2012 (p < 0.001). Mean number of injections given in one year was 11.8 in 2018 versus 10.4 in 2012 (p < 0.001). After one year, a majority of eyes in both groups still received treatment at 4-week intervals. CONCLUSION: The study suggests that the possibility of switching eyes with treatment-resistant nAMD to aflibercept leads to a modest visual benefit compared with continuing first-line bevacizumab therapy.
Assuntos
Bevacizumab/administração & dosagem , Resistência a Medicamentos , Substituição de Medicamentos/métodos , Macula Lutea/diagnóstico por imagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Tomografia de Coerência Óptica/métodos , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Inibidores da Angiogênese/administração & dosagem , Feminino , Humanos , Injeções Intravítreas , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnósticoAssuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Substituição de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Azetidinas/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Oximas/administração & dosagem , Piperidinas/administração & dosagem , Prognóstico , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Vemurafenib/administração & dosagemRESUMO
BACKGROUND: Monoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis. METHODS: Between September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1. low-risk patients (HBeAg-negative and HBV DNA < 12 IU/mL before LT) were due to withdraw from HBIg once HBsAg had become negative after a minimum of 7 days of HBIg+NA; 2. high-risk patients were due to receive HBIg for at least 6 months, after which they continued with third-generation NA monotherapy, only. RESULTS: Twenty patients with a median interquartile range (IQR) follow-up of 46 (64-39) months were enrolled in the study (40% receiving ETV, 60% receiving TDF). Two low-risk patients refused early HBIg withdrawal and were therefore treated and analyzed along with the high-risk group. Eventually, there were 2 groups: group A, which included 12 low-risk patients, and group B, which included 8 patients (six high-risk, 2 low-risk). After transplantation, group A and B patients received HBIg+NA for a median (IQR) time of 7 (9-7) days and 9 (13-5) months, respectively. All 20 recipients demonstrated HBV DNA < 12 IU/mL and stable graft function during follow-up. Two patients (10%), 1 from each group, had HBsAg relapse. Notably, both patients who relapsed had hepatocellular carcinoma (HCC) diagnosed before LT and showed very low levels (< 0.25 IU/mL) of HBsAg after recurrence. CONCLUSION: In low-risk HBsAg-positive recipients, HBIg may be safely discontinued within 2 weeks of LT and replaced by ETV or TDF monotherapy.
Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B/prevenção & controle , Transplante de Fígado , Reinfecção/prevenção & controle , Tenofovir/administração & dosagem , Adulto , Substituição de Medicamentos/métodos , Feminino , Seguimentos , Guanina/administração & dosagem , Hepatite B/complicações , Vírus da Hepatite B , Humanos , Imunoglobulinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVES: We sought to evaluate perceptions of biosimilar products among US rheumatologists who prescribe TNF-α inhibitors, given that 10 TNF-α inhibitor biosimilars and two rituximab biosimilars have Food and Drug Administration (FDA) approval. METHODS: A 19-question self-administered online survey was conducted from 6 May to 1 June 2019, and fielded by WebMD, LLC. Rheumatologists (n = 9050) who were members of Medscape.com and its partner panels were invited to participate. Likert and other rating scales were used to collect responses, which were summarized descriptively. RESULTS: Responses were obtained from 320 board-certified US rheumatologists, 85% of whom were fellows of the ACR. Nearly all respondents were familiar with the FDA definition of a biosimilar product and were aware that an infliximab biosimilar was FDA approved; fewer realized that adalimumab, etanercept and rituximab biosimilars were also FDA approved. Most respondents (84%) were aware that an approved biosimilar was not automatically deemed interchangeable by the FDA. Rheumatologists were more likely to initiate biosimilar treatment for a biologic treatment-naïve patient with RA (73%) than they were to switch to the biosimilar for a patient with RA doing well on the reference product (35%). CONCLUSIONS: The results of this survey suggest that US rheumatologists have a good understanding and acceptance of biosimilar products, particularly for the initiation of treatment in biologic-naïve individuals. They were hesitant to switch from a reference product to a biosimilar for a patient doing well on the reference product. Additional education on biosimilars is required to help inform treatment decisions by rheumatologists. A plain language summary of this article has been uploaded as supplementary material, available at Rheumatology online.
Assuntos
Atitude do Pessoal de Saúde , Medicamentos Biossimilares/farmacologia , Substituição de Medicamentos/métodos , Doenças Reumáticas/tratamento farmacológico , Reumatologistas , Rituximab/farmacologia , Inibidores do Fator de Necrose Tumoral/farmacologia , Antirreumáticos/farmacologia , Cultura , Aprovação de Drogas/métodos , Humanos , Avaliação das Necessidades , Reumatologistas/psicologia , Reumatologistas/estatística & dados numéricos , Percepção Social , Estados UnidosRESUMO
Initial management of diabetic macular edema (DME) is well-defined, but there is a lack of national or international consensus for patients who do not respond or respond only partially to these treatments. Several studies, mostly retrospective, have assessed medication switches, but currently, the literature contains no randomized studies. The goal of this article is to present an algorithm for switching medications, which can be proposed to DME patients treated with anti-VEGF agents, as defined by a group of French retina experts, supported by the existing literature on the subject. After initiation of an anti-VEGF treatment for DME, the response is usually assessed after 5 monthly injections. A partial anatomical response (reduction of central retinal thickness between 10 and 20%), seen in 30 to 40% of patients, is associated with a favorable visual prognosis according to randomized studies. Continuation of the anti-VEGF injections after the induction phase is thus possible. If the response remains incomplete after 3 additional anti-VEGF injections, a complete ophthalmologic examination should be performed, and a switch to another therapeutic class (corticosteroids) may be proposed in the absence of contraindications. If a complete non-response is seen initially (reduction of central retinal thickness<10%), the switch is proposed immediately after the induction phase.
Assuntos
Algoritmos , Retinopatia Diabética/tratamento farmacológico , Substituição de Medicamentos/normas , Edema Macular/tratamento farmacológico , Guias de Prática Clínica como Assunto , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Retinopatia Diabética/epidemiologia , Substituição de Medicamentos/métodos , Substituição de Medicamentos/estatística & dados numéricos , Humanos , Injeções Intravítreas , Edema Macular/epidemiologia , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Estudos RetrospectivosAssuntos
Dor nas Costas , Denosumab/uso terapêutico , Vértebras Lombares , Osteoporose Pós-Menopausa , Fraturas da Coluna Vertebral , Vértebras Torácicas , Suspensão de Tratamento/normas , Dor nas Costas/diagnóstico , Dor nas Costas/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Diagnóstico Diferencial , Substituição de Medicamentos/métodos , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Risco Ajustado/métodos , Prevenção Secundária/métodos , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Ácido Zoledrônico/administração & dosagemRESUMO
BACKGROUND: Recurrent pericarditis (RP) is a complication (15-30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1ß and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab. CASE PRESENTATION: The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare. The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient's poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up. CONCLUSIONS: We describe two cases of failure of the treatment with anti-IL-1ß monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.
Assuntos
Anticorpos Monoclonais Humanizados , Substituição de Medicamentos/métodos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1beta/antagonistas & inibidores , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pericardite/etiologia , Pericardite/imunologia , Pericardite/fisiopatologia , Pericardite/terapia , Recidiva , Resultado do TratamentoRESUMO
Non-response to intravitreal ranibizumab represents a frequent problem in pachychoroid neovasculopathy (PNV). To investigate the effectivity of switching to aflibercept, the database of the Ludwig Maximilians University, Munich, was screened for patients fulfilling the following inclusion criteria: (i) diagnosis of PNV; (ii) inadequate response to ≥ 3 ranibizumab injections, in spite of monthly dosing, defined as persistence of subretinal-fluid four weeks after the last ranibizumab injection; (iii) resulting switch to aflibercept administered as three monthly injections. Primary outcome measure was percentage of eyes with a dry macula four weeks after the third aflibercept injection. Secondary outcome measures included changes in maximum subretinal fluid (SRF), central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). In total, 14 eyes of 14 patients were included. Mean age was 64.1 ± 7.5 (range: 51-78) years. Switching to aflibercept was performed after mean 8.4 ± 4.1 (3-15) ranibizumab injections. While no eye (0%) achieved a dry macula status during ranibizumab treatment, switching to aflibercept achieved a dry macula status in eight eyes (57.1%) after three injections. While both ranibizumab and aflibercept showed an effect on CST (p = 0.027, p = 0.003), only aflibercept showed a significant effect on SRF (p = 0.0009) and SFCT (p = 0.044). In cases of PNV not responding to intravitreal ranibizumab, switching treatment to aflibercept induces a favorable short-term response resolving persistent fluid and achieving a dry macula. Further studies with longer follow-up are warranted.