RESUMEN

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.

Asunto(s)

Inhibidores de la Angiogénesis , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Anciano , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatología , Inhibidores de la Angiogénesis/administración & dosificación , Anciano de 80 o más Años , Sustitución de Medicamentos/métodos , Resultado del Tratamiento , Estudios de Seguimiento , Angiografía con Fluoresceína/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Fondo de Ojo

RESUMEN

OBJECTIVES: To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. METHODS: RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. RESULTS: A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). CONCLUSION: In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

Asunto(s)

Adalimumab , Antirreumáticos , Teorema de Bayes , Biosimilares Farmacéuticos , Comorbilidad , Humanos , Biosimilares Farmacéuticos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Adulto , Adalimumab/uso terapéutico , Sustitución de Medicamentos/estadística & datos numéricos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Anciano , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Musculoesqueléticas/tratamiento farmacológico , Resultado del Tratamiento

RESUMEN

Mild psoriasis may be burdensome; if symptoms are inadequately controlled, switching therapy may be warranted. In the Phase 3 NAVIGATE trial, patients with moderate-to-severe plaque psoriasis received ustekinumab for 16 weeks. Patients with inadequate response (Investigator's Global Assessment [IGA] ≥ 2) were randomized to switch to guselkumab or continue ustekinumab. This post-hoc analysis evaluated the patient subgroup with residual mild psoriasis (IGA = 2) after initial ustekinumab therapy. Outcomes assessed included the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Psoriasis Symptoms and Signs Diary (PSSD). Initially, 871 patients received ustekinumab. At Week 16, 161 randomized patients had residual mild psoriasis (IGA = 2). Among guselkumab- vs ustekinumab-treated patients at Week 28, 59.0% vs 27.7% achieved PASI 90, and 50.0% vs 21.0% achieved DLQI 0/1. Mean changes from baseline in PSSD score were -44 vs -28 and -50 vs -32, respectively, with thresholds of -40 considered clinically meaningful. Mean changes in PSSD itch score were -4.6 vs -2.9, with reductions ≥ 4.0 considered clinically meaningful. Treatment differences were maintained/increased through Week 52. Among patients with residual mild psoriasis after 16 weeks of ustekinumab, those switching to guselkumab had greater improvements in skin clearance, health-related quality of life, and patient-reported symptoms and signs than those continuing ustekinumab.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Fármacos Dermatológicos , Sustitución de Medicamentos , Medición de Resultados Informados por el Paciente , Psoriasis , Calidad de Vida , Índice de Severidad de la Enfermedad , Ustekinumab , Humanos , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Resultado del Tratamiento , Femenino , Masculino , Adulto , Persona de Mediana Edad , Factores de Tiempo , Inducción de Remisión

RESUMEN

Purpose: To examine the changes in aqueous humor cytokine levels and clinical outcomes of switching from aflibercept to faricimab in eyes with neovascular age-related macular degeneration (nAMD). Methods: Fifty-four eyes of 54 patients with AMD undergoing treatment with aflibercept under a treat-and-extend (TAE) regimen were switched to faricimab and studied prospectively. Best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status were analyzed using optical coherence tomography. Aqueous humor was collected before and after the switch, and angiopoietin-2 (Ang-2), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) A levels were measured. Results: After switching from aflibercept to faricimab, exudative changes improved in 28 eyes (52%), remained stable in eight eyes (15%), and worsened in 18 eyes (33%). BCVA changed from 0.27 ± 0.31 to 0.26 ± 0.29 (P = 0.46), CRT decreased from 306.2 ± 147.5 µm to 278.6 ± 100.4 µm (P = 0.11), and CCT changed from 189.5 ± 92.8 µm to 186.8 ± 93.9 µm (P = 0.21). VEGF-A levels were below the detection sensitivity in many cases throughout the pre- and post-switching periods. Ang-2 significantly decreased from 23.8 ± 23.5 pg/mL to 16.4 ± 21.9 pg/mL (P < 0.001), and PlGF significantly increased from 0.86 ± 0.85 pg/mL to 1.72 ± 1.39 pg/mL (P < 0.001). Conclusions: Switching from aflibercept to faricimab in patients with nAMD may not only suppress VEGF-A but also Ang-2 and reduce exudative changes.

Asunto(s)

Inhibidores de la Angiogénesis , Humor Acuoso , Citocinas , Inyecciones Intravítreas , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda , Humanos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Humor Acuoso/metabolismo , Masculino , Femenino , Anciano , Estudios Prospectivos , Agudeza Visual/fisiología , Tomografía de Coherencia Óptica/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/uso terapéutico , Anciano de 80 o más Años , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/metabolismo , Degeneración Macular Húmeda/fisiopatología , Citocinas/metabolismo , Angiopoyetina 2/metabolismo , Sustitución de Medicamentos , Factor de Crecimiento Placentario/metabolismo , Persona de Mediana Edad

RESUMEN

The real-world outcomes of lonoctocog alfa (rVIII-SingleChain), a long-acting factor VIII (FVIII) with a favorable safety and efficacy profile in trials, were assessed in patients with hemophilia A in Iberian (Spain and Portugal). This was a retrospective study involving patients switching to rVIII-SingleChain from other FVIIIs in 7 Spanish and Portuguese hospitals. The efficacy and safety of replacement therapies were compared between 12 months before switching and the period from switching to the end of the study. Twenty-nine patients (median age 25 years; severe hemophilia A, 37.9%) were recruited. Before switching, 12 were on prophylaxis and were followed-up for a median of 12 months. After switching, 17 received prophylaxis with rVIII-SingleChain and were followed-up for a median of 41 months. Those with ≤2 weekly infusions increased from 37.5% before switching to 60.7% after switching to rVIII-SingleChain. The median monthly consumption was 312 IU/kg with prior FVIIIs and 273 IU/kg with rVII-SingleChain. Six spontaneous bleeds were reported in each period in the prophylaxis patients. In the entire cohort, 50 bleeds were reported with prior FVIIIs and 33 were reported after switching to rVIII-SingleChain. Patients requiring ≤1 dose for hemostasis increased from 44.0% with prior FVIIIs to 60.6% with rVIII-SingleChain. Responses were rated good/excellent in 95.4% of cases. No safety concerns were reported. Patients who switched to rVIII-SingleChain prophylaxis had excellent bleeding control and reduced infusion frequency in regular clinical practice, with the subsequent increase in quality-of-life.

Asunto(s)

Factor VIII , Hemofilia A , Humanos , Hemofilia A/tratamiento farmacológico , Estudios Retrospectivos , Adulto , Masculino , España , Factor VIII/uso terapéutico , Factor VIII/administración & dosificación , Adulto Joven , Portugal , Adolescente , Persona de Mediana Edad , Hemorragia , Resultado del Tratamiento , Niño , Sustitución de Medicamentos , Femenino

RESUMEN

INTRODUCTION: The transition from fingolimod (FIN) to siponimod (SIP) for Multiple Sclerosis (MS) treatment in the occurrence of Secondary Progressive Multiple Sclerosis (SPMS) diagnosis has increasingly attracted considerable interest in the recent literature. METHODS: We evaluated the efficacy and safety of a direct switch from FIN to SIP in nine MS patients who had switched directly from FIN to SIP due to SPMS diagnosis at the Multiple Sclerosis Center of the University Hospital Policlinico of Bari. RESULTS AND CONCLUSION: Real-world results from our cohort demonstrated that the direct switch from FIN to SIP in patients transitioning in SP course is associated with clinical and disability progression stability, with a favorable safety profile.

Asunto(s)

Compuestos de Bencilo , Clorhidrato de Fingolimod , Esclerosis Múltiple Crónica Progresiva , Humanos , Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Compuestos de Bencilo/uso terapéutico , Azetidinas/uso terapéutico , Nortropanos , Inmunosupresores/uso terapéutico , Sustitución de Medicamentos , Progresión de la Enfermedad , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Resultado del Tratamiento

Asunto(s)

Trastorno Depresivo Mayor , Inhibidores Selectivos de la Recaptación de Serotonina , Inhibidores de Captación de Serotonina y Norepinefrina , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/farmacología , Sustitución de Medicamentos , Antidepresivos/efectos adversos , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/administración & dosificación

RESUMEN

INTRODUCTION: This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA). METHODS: Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May 2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6 months from treatment switch. Fatigue and treatment adherence were measured ≥ 6 months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA. RESULTS: Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111). CONCLUSION: Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Compuestos Heterocíclicos con 3 Anillos , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Estudios Transversales , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Anciano , Sustitución de Medicamentos/estadística & datos numéricos , Adulto , Índice de Severidad de la Enfermedad

RESUMEN

BACKGROUND: There is a need to understand health care resource utilization (HCRU) and costs associated with treatment-experienced people with HIV (PWH) switching treatment regimens. OBJECTIVE: To describe HCRU and cost during lines of antiretroviral therapy (ART) for treatment-experienced PWH switching to or restarting guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multitablet regimens and single-tablet regimens. METHODS: This retrospective claims study used data from Optum Research Database (January 1, 2010, to March 31, 2020) to identify lines of therapy (LOTs) for treatment-experienced adults who switched to or restarted INSTI-based regimens between January 1, 2018, and December 31, 2019. The first LOT during the study period was included in the analysis. We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). Analysis of HCRU by site of service was conducted following inverse probability treatment weighting. Multivariable regression was conducted using a generalized linear model with stepwise covariate selection to estimate HIV-related medical costs and control for remaining differences after inverse probability treatment weighting. RESULTS: 4,251 PWH were identified: B/F/TAF (n = 2,727; 64.2%), DTG/ABC/3TC (n = 898; 21.1%), DTG+FTC/TAF (n = 539; 12.7%), and DTG+FTC/TDF (n = 87; 2.1%). PWH treated with DTG+FTC/TAF had a significantly higher mean of all-cause ambulatory visits than PWH treated with B/F/TAF (1.8 vs 1.6, P < 0.001). A significantly smaller proportion of PWH treated with DTG/ABC/3TC had an all-cause ambulatory visit vs PWH treated with B/F/TAF (90.6% vs 93.9%, P < 0.001). All-cause total costs were not significantly different between regimens. Mean (SD) medical HIV-related costs per month during the LOT were not significantly different between B/F/TAF $699 (3,602), DTG/ABC/3TC $770 (3,469), DTG+FTC/TAF $817 (3,128), and DTG+FTC/TDF $3,570 (17,691). After further controlling for unbalanced measures, HIV-related medical costs during the LOT were higher (20%) but did not reach statistical significance for DTG/ABC/3TC (cost ratio = 1.20, 95% CI = 0.851-1.694; P = 0.299), 49% higher for DTG+FTC/TAF (cost ratio = 1.489, 95% CI = 1.018-2.179; P = 0.040), and almost 11 times greater for DTG+FTC/TDF (cost ratio = 10.759, 95% CI = 2.182-53.048; P = 0.004) compared with B/F/TAF. CONCLUSIONS: HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Piridonas , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Piridonas/economía , Piridonas/uso terapéutico , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/economía , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Tenofovir/uso terapéutico , Tenofovir/economía , Aceptación de la Atención de Salud/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Combinación de Medicamentos , Oxazinas/uso terapéutico , Oxazinas/economía , Emtricitabina/uso terapéutico , Emtricitabina/economía , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/economía , Piperazinas/economía , Piperazinas/uso terapéutico , Lamivudine/economía , Lamivudine/uso terapéutico , Inhibidores de Integrasa VIH/economía , Inhibidores de Integrasa VIH/uso terapéutico , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Sustitución de Medicamentos/economía , Amidas , Ciclopropanos , Didesoxiadenosina/análogos & derivados

RESUMEN

INTRODUCTION: there is a lack of research evaluating the impact of therapeutic switching from human insulin to analogues, particularly in paediatric populations from low- and middle-income countries. AIM: The study aimed to retrospectively assess the effectiveness and safety of transitioning from human insulin to insulin analogs in Tunisian children with diabetes. METHODS: This retrospective descriptive study included children with type 1 diabetes who changed their insulin therapy protocol after at least one year of treatment with human insulin. Clinical, therapeutic, and glycaemic homeostasis parameters were assessed following the transition from human insulin (NPH + rapid-acting insulin) to the Basal-Bolus insulin analog- protocol. RESULTS: The study included 60 patients. Following the switch, all patients showed a significant reduction in mean fasting blood glucose levels (11.11 mmol/l vs. 8.62 mmol/l; p=0.024). Glycated haemoglobin A1C levels decreased notably in children who adhered to their diet (from 9.93% to 8.38%; p=0.06) and/or engaged in regular physical activity (from 10.40% to 8.61%; p=0.043). The average number of hypoglycemic events per year decreased from 4.03 events/year to 2.36 events/year (p=0.006), along with a decrease in the rate of patients hospitalized for acid-ketotic decompensation (from 27% to 10%; p=0.001). Financial constraints led to 82% of patients reusing microfine needles ≥2 times per day, and 12% were compelled to revert to the initial insulin therapy protocol due to a lack of access to self-financed microfine needles or discontinued social coverage. CONCLUSIONS: Although insulin analogues offer clear benefits, their use poses challenges as a therapeutic choice for children with diabetes in low- to middle-income countries. These challenges hinder the achievement of optimal glycemic control goals.

Asunto(s)

Glucemia , Diabetes Mellitus Tipo 1 , Hipoglucemiantes , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/sangre , Túnez/epidemiología , Niño , Estudios Retrospectivos , Masculino , Femenino , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/análogos & derivados , Insulina/uso terapéutico , Adolescente , Glucemia/análisis , Glucemia/efectos de los fármacos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Resultado del Tratamiento , Sustitución de Medicamentos/estadística & datos numéricos , Preescolar , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control

RESUMEN

BACKGROUND: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at 6 months after lemborexant initiation. RESULTS: The success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, the success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). CONCLUSION: The proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging.

Asunto(s)

Bases de Datos Factuales , Hipnóticos y Sedantes , Pautas de la Práctica en Medicina , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Hipnóticos y Sedantes/uso terapéutico , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Anciano , Japón , Adulto , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estudios de Cohortes , Quimioterapia Combinada , Sustitución de Medicamentos/estadística & datos numéricos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Adulto Joven , Pirimidinas

RESUMEN

BACKGROUND: Patients often use manufacturer-sponsored coupons to reduce their out-of-pocket spending. However, little is known whether coupon use is associated with medication-switching behaviors. OBJECTIVE: To examine if using a manufacturer-sponsored coupon to initiate a medication is associated with patterns of medication-switching behaviors among patients with type 2 diabetes. METHODS: Using IQVIA's retail pharmacy claims data from October 2017 to September 2019, we analyzed commercially insured patients with type 2 diabetes who had newly started taking the following noninsulin diabetes drugs: generic metformin (nearly no coupon use), Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors (SGLT2, high coupon use), and dipeptidyl peptidase IV inhibitors (DPP-IV inhibitors, moderate coupon use). We assessed if drug-switching behaviors, defined as no switching, switching to a same-class drug, or switching to a drug in a different class, differed among patients who did and did not use coupons to initiate treatments. We performed multinomial logistic regression to estimate the probability of each switching type associated with patients' initial coupon use. RESULTS: Among 9,781 patients in our sample, 83.7% of them initiated treatments with metformin, 8.2% with SGLT2, and 8.1% with DPP-IV inhibitors. The overall switching rate was the lowest for generic metformin (40%) than brand-name drugs (56%-57%). Among the brand-name drug users, patients who used a coupon to initiate these drugs were less likely to switch to any drug compared with patients without coupon use (SGLT2 = -18% [95% CI = -24% to -13%]; DPP-IV inhibitors = -9% [-16% to -2%]). These patients were also less likely to switch to drugs in other competing classes (SGLT2 = -16% [95% CI = -22% to -10%]; DPP-IV inhibitors = -9% [-16% to -2%]). CONCLUSIONS: Patients who started their treatment with generic metformin had the lowest rate of drug switching. Using coupons to initiate brand-name drugs in classes with prevalent coupons was associated with reduced medication switching to other class drugs.

Asunto(s)

Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Femenino , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Anciano , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Sustitución de Medicamentos , Industria Farmacéutica/economía , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Medicamentos Genéricos/uso terapéutico , Adulto , Gastos en Salud

RESUMEN

BACKGROUND: Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV. METHODS: We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group). Participants in the exposed group were matched 1:2 to individuals continuing stable non-doravirine-containing ART, on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4-count, pre-ART plasma viral load (PVL) and anchor drug class before switching. The primary outcome was protocol-defined virological failure (PDVF; PVL of ≥200 copies per mL) in the intention-to-treat (ITT) population at week 104, with participants modifying their regimen or becoming lost to follow-up considered as PDVF (non-inferiority margin +5%). In contrast, in the on-treatment population, those who modified their regimen or became lost to follow-up were censored from that moment onwards. Tolerability was a secondary outcome. FINDINGS: In total, 590 participants in the exposed group and 1180 participants in the unexposed group (of whom 55·3% used integrase strand transfer inhibitor-based regimens) were included. In the ITT analysis, PDVF occurred in 135 (22·9%) exposed participants and in 295 (25·0%) unexposed participants (risk difference -2·12%, upper limit of the one-sided 95% CI +1·40%). In the on-treatment analysis, 10 (2·2%) of 455 non-censored exposed participants and 26 (2·9%) of 885 non-censored unexposed participants had PDVF (risk difference -0·70%, upper limit of the one-sided 95% CI +0·73%). All exposed participants with a PVL of 200 copies or more per mL resuppressed without regimen modification: no confirmed virological failure (two consecutive PVLs of ≥200 copies per mL) was observed. 104 (17·6%) exposed participants and 211 (17·9%) unexposed participants modified their regimen. 73 (12.4%) exposed participants discontinued doravirine due to adverse events: abnormal dreams (1·7%) and insomnia (1·5%) were most common. INTERPRETATION: Switching to doravirine in well suppressed people with HIV without previous virological failure was non-inferior compared with continuing non-doravirine-containing regimens after 2 years in a real-world setting. FUNDING: None.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Piridonas , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Femenino , Estudios Prospectivos , Adulto , Carga Viral/efectos de los fármacos , Persona de Mediana Edad , Piridonas/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Triazoles/uso terapéutico , Triazoles/efectos adversos , Sustitución de Medicamentos , Resultado del Tratamiento , Recuento de Linfocito CD4

RESUMEN

INTRODUCTION: Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment. OBJECTIVES: To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. MATERIALS AND METHODS: An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. RESULTS: A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n=315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p=0.030), with a history of depression (p=0.003) and positive for RF at baseline (p=0.014) in the switch group. In the multivariate analysis, anti-TNF-α agents use (OR 8.3, 95% CI 2.4-28.8, p=0.001), tobacco exposure (OR 2.3, 95% CI 1.1-4.8, p=0.02) and history of depression (OR 3.1, 95% CI 1.3-7.7) seem to predict the need to switch in the first year of treatment due to ineffectiveness. DISCUSSION AND CONCLUSION: In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Sustitución de Medicamentos , Insuficiencia del Tratamiento , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Factores de Riesgo , Anciano , Adulto , Factores de Tiempo

RESUMEN

This study presents a safety analysis of infusion reactions (IRs) in gastric cancer patients who switched from reference trastuzumab to its biosimilar, trastuzumab-NK, at the Saitama Cancer Center in Japan from April 2018 to March 2022. IRs were identified if patients developed symptoms such as fever, chills, infusion-related reactions, hypersensitivity, rash, pruritus, urticaria, systemic disorders, or immune system disorders on the day of administration or the following day. The incidence of IRs was 14% in the reference trastuzumab group, 33% in the trastuzumab-NK group, and 33% in the switching group. There was no significant difference in IR incidence between the reference trastuzumab and trastuzumab-NK groups (p = 0.235). Among the switching group, only one of the three patients who experienced an IR had a reaction associated with the switch. These findings suggest that the frequency of IRs in the switching group gastric cancer is comparable to the other groups, indicating that switching is a viable treatment option with appropriate management. Additionally, 37 of the 45 patients in the study were male, provides new safety information on switching in gastric cancer for male patients that has not been previously reported.

Asunto(s)

Biosimilares Farmacéuticos , Receptor ErbB-2 , Neoplasias Gástricas , Trastuzumab , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/efectos adversos , Trastuzumab/uso terapéutico , Masculino , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Femenino , Persona de Mediana Edad , Anciano , Receptor ErbB-2/metabolismo , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Adulto , Japón , Anciano de 80 o más Años , Sustitución de Medicamentos , Infusiones Intravenosas

RESUMEN

BACKGROUND: A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking. OBJECTIVE: The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations. METHODS: We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres. RESULTS: Altogether, 103 patients (26 Crohn's disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients ( P  = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P  < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml). CONCLUSION: Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Enfermedad de Crohn , Fármacos Gastrointestinales , Quimioterapia de Mantención , Sistema de Registros , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Femenino , Masculino , Adulto , Estudios Retrospectivos , Colitis Ulcerosa/tratamiento farmacológico , Fármacos Gastrointestinales/administración & dosificación , Fármacos Gastrointestinales/sangre , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/farmacocinética , Persona de Mediana Edad , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/sangre , Inyecciones Subcutáneas , Resultado del Tratamiento , Sustitución de Medicamentos , Infusiones Intravenosas , Administración Intravenosa , Adulto Joven , Factores de Tiempo

RESUMEN

Palmoplantar pustulosis (PPP) is a chronic inflammatory recurrent disease characterized by sterile pustules involving palms and/or feet. Presently, there are no standard recommended treatment regimens. Tofacitinib is an oral Janus kinase (JAK) inhibitor, mainly acts on JAK 1 and 3 and has been approved for the treatment of rheumatoid arthritis in adults. Herein, we present a case of a patient with PPP who did not respond to IL-17A inhibitor secukinumab but was successfully treated by the JAK inhibitor tofacitinib.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Inhibidores de las Cinasas Janus , Piperidinas , Psoriasis , Pirimidinas , Humanos , Pirimidinas/uso terapéutico , Piperidinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Psoriasis/tratamiento farmacológico , Sustitución de Medicamentos , Interleucina-17/antagonistas & inhibidores , Pirroles/uso terapéutico , Femenino , Masculino , Resultado del Tratamiento , Persona de Mediana Edad

RESUMEN

BACKGROUND: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are similar disease-modifying therapies (DMTs) that reduce disease activity in patients with relapsing-remitting multiple sclerosis (MS). We expect that patients on DRF would experience a similar incidence and severity of lymphopenia, given that it is a well-documented side effect of DMF treatment. METHODS: We utilized linear mixed-effects models to test for differences in white blood cell count (WBC), absolute lymphocyte count (ALC), absolute CD3+ count, absolute CD4+ count, and absolute CD8+ count over time in clinically stable patients with MS on DMF who switched to DRF. RESULTS: Twenty-two patients with MS who were clinically stable on DMF switched to DRF. Linear mixed-effects models showed a decrease in ALC when switching medications (ß = -225.70, p < 0.040). In addition, the models showed a decrease in absolute CD8+ counts after switches from DMF to DRF (ß = -85.59, p = 0.034). CONCLUSION: Patients with MS who are stable on DMF and switch to DRF may experience worsening of lymphopenia and lower absolute CD8+ counts, which may increase their risk of opportunistic infections. These findings indicate that close lymphocyte subset monitoring is clinically important when switching patients with MS from DMF to DRF.

Asunto(s)

Dimetilfumarato , Inmunosupresores , Linfopenia , Esclerosis Múltiple Recurrente-Remitente , Humanos , Dimetilfumarato/efectos adversos , Linfopenia/inducido químicamente , Femenino , Masculino , Adulto , Inmunosupresores/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Persona de Mediana Edad , Recuento de Linfocitos , Sustitución de Medicamentos

Asunto(s)

Antiparkinsonianos , Indoles , Enfermedad de Parkinson , Parche Transdérmico , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/uso terapéutico , Masculino , Femenino , Indoles/administración & dosificación , Persona de Mediana Edad , Administración Oral , Anciano , Resultado del Tratamiento , Sustitución de Medicamentos

RESUMEN

With the continued development of biologics for the treatment of psoriasis, some patients have achieved optimal control, but a recommended biologic sequence if a biologic fails to initially improve the skin, termed primary nonresponse, or loses efficacy after initial improvement, termed secondary nonresponse, is still lacking. Primary and secondary nonresponse can occur with any class of biologics, and the type of nonresponse can drive the choice of whether to switch within a biologic class or to a different biologic class. The choice of biologic can also be challenging when managing psoriasis and concomitant psoriatic arthritis, as treatment differs on the basis of the severity of both diseases and further classification of axial and peripheral joint involvement. When choosing a biologic, each patient's comorbidities and preferences are also taken into account to provide the optimal therapy. With this lack of an established biologic sequence after biologic failure, the objective of our review is to define a therapy sequence for the tumor necrosis factor (TNF), interleukin-17 (IL-17), and interleukin-23 (IL-23) inhibitor classes in the treatment of psoriasis and psoriatic arthritis. Our proposed biologic sequence was derived through an analysis of the efficacy of each biologic class, primary and secondary nonresponse rates from clinical trials, and clinical experience with expert opinion.

Asunto(s)

Artritis Psoriásica , Productos Biológicos , Interleucina-17 , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Productos Biológicos/uso terapéutico , Productos Biológicos/administración & dosificación , Interleucina-17/antagonistas & inhibidores , Artritis Psoriásica/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Resultado del Tratamiento , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Índice de Severidad de la Enfermedad , Sustitución de Medicamentos , Insuficiencia del Tratamiento