RESUMEN
BACKGROUND: Anti-vascular endothelial growth factors (VEGFs) treatment has been associated with an increased risk of thromboembolic events. Therefore, the use of anti-VEGFs for patients with colorectal cancers (CRC) has raised concerns about the potential risk of retinal vein occlusion (RVO), an ocular disease caused by embolism or venous stasis. This study aims to evaluate the risk of RVO in patients with CRC treated with anti-VEGFs. METHOD: We conducted a retrospective cohort study using the Taiwan Cancer Registry and National Health Insurance Database. The study cohort comprised patients newly diagnosed with CRC between 2011 and 2017, who received anti-VEGF treatment. For each patient in the study cohort, a control group comprising four patients newly diagnosed with CRC, but not receiving anti-VEGF treatment, was randomly selected. A washout period of 12 months was implemented to identify new cases. The index date was defined as the date of the first prescription of anti-VEGF drugs. The study outcome was the incidence of RVO, as identified by ICD-9-CM (362.35 and 362.36) or ICD-10-CM codes (H3481 and H3483). Patients were followed from their index date until the occurrence of RVO, death or the end of the study period. Covariates, including patients' age at index date, sex, calendar year of CRC diagnosis, stage of CRC and comorbidities related to RVO, were included. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with adjustments for all covariates to compare the risk of RVO between the anti-VEGF and control groups. RESULTS: We recruited 6285 patients in the anti-VEGF group and 37,250 patients in the control group, with mean ages of 59.49 ± 12.11 and 63.88 ± 13.17 years, respectively. The incidence rates were 1.06 per 1000 person-years for the anti-VEGF group, and 0.63 per 1000 person-years for the controls. There was no statistically significant difference in RVO risk between the anti-VEGF and control groups (HR: 2.21, 95% CI: 0.87-5.61). CONCLUSION: Our results indicated no association between use of anti-VEGF and occurrence of RVO among CRC patients, although the crude incidence rate of RVO was higher in patients receiving anti-VEGF, compared to control patients. Future study with larger sample size is required to confirm our findings.
Asunto(s)
Neoplasias Colorrectales , Oclusión de la Vena Retiniana , Tromboembolia , Humanos , Persona de Mediana Edad , Anciano , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/epidemiología , Estudios de Cohortes , Estudios Retrospectivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/epidemiologíaRESUMEN
BACKGROUND: Amyloidosis is a rare, progressive and variable group of diseases characterized by extracellular deposits of amyloid protein in different tissues and organs. It is a protein-misfolding disease in which small proteins of about 10 to 15 kDa acquire an alternative and relatively misfolded state at minimum energy and subsequently aggregate into oligomers and polymers. It mimics other eyelid diseases, such as involutional ptosis, eyelid granulomatous or cancerous lesions. Misdiagnosis of eyelid amyloidosis is usual when the lesion grows slowly and insidiously. Definite diagnosis depends on clinical suspicion and tissue-proven biopsy. CASE PRESENTATION: A 50-year-old female had painless progressive ptosis in both eyes for 6 months. She presented with limited upward gaze due to swelling of the upper eyelids OU. She complained of mild foreign body sensation. Upon examination, we observed an infiltrated irregular yellowish mass on the surface of her upper palpebral conjunctiva in both eyes. The mass was non-movable without tenderness. We performed excisional biopsy for the masses and subsequent histopathology of the biopsy specimens revealed amyloidosis. Systemic workup showed no other lesions. Unfortunately, her ptosis and upward gaze restriction was not improved after the operation. However, the masses did not enlarge in the following 3 months. CONCLUSIONS: The varied presentations of ocular adnexal and orbital amyloidosis often lead to a significant delay between first symptoms and diagnosis. Immediate confirmatory biopsy and subsequent systemic workup should be performed whenever amyloidosis is highly suspected.
Asunto(s)
Amiloidosis , Blefaroptosis , Enfermedades de la Conjuntiva , Enfermedades de los Párpados , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Amiloidosis/complicaciones , Amiloidosis/diagnóstico , Blefaroptosis/diagnóstico , Blefaroptosis/etiología , Enfermedades de los Párpados/diagnóstico , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: The association between cardioprotective aspirin and risk of age-related macular degeneration (AMD) is still controversial up to date. We aimed to analyze the risk of AMD between aspirin users and non-aspirin users. METHOD: This was a retrospective cohort study by using claims data from the National Health Insurance Research Database. Patients aged more than 45 years old who initiated aspirin during 2002 to 2012 were followed till 2013. We first selected an age and sex-matched cohort, then identified aspirin users and non-aspirin users as propensity score-matched cohort. Cox proportional hazard regression model was applied to compare their hazards and 95% confidence intervals. Incidence of newly developed AMD, neovascular AMD, and other-AMD was calculated. RESULTS: We identified 204 085 regular aspirin users and 478 048 non-aspirin users from our datasets. The univariate HR was 2.85 (95% CI, 2.75-2.96), and the multivariate HR was 2.54 (95% CI, 2.44-2.65). In the PS-matched cohort, the HR was 2.38 (95% CI, 2.25-2.52). The incidence of aspirin users for AMD risk was 11.95 per 1000 person-year, while the incidence of non-aspirin users was only 3.92 per 1000 person-year. CONCLUSION: Patients with regular use of aspirin had higher risk in developing AMD compared to non-aspirin users and suggest to have regular visual acuity and funduscopic examination.
Asunto(s)
Aspirina , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis , Aspirina/efectos adversos , Estudios de Cohortes , Humanos , Incidencia , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Factor A de Crecimiento Endotelial Vascular , Agudeza VisualRESUMEN
PURPOSE: Case presentation of newly diagnosed systemic lupus erythematosus (SLE) presenting initially as Tolosa-Hunt syndrome (THS). STUDY DESIGN: Retrospective clinical case. METHOD: Case report. RESULTS: A healthy young man developed acute binocular diplopia within 2 days without other neurological deficits. Bilateral 6th cranial nerve palsy was observed with general reduction in the visual field test. Emergent brain magnetic resonance image (MRI) was performed, which revealed severe inflammation in the cavernous sinus, superior orbital fissure, and apex of the orbit. No cavernous thrombosis or intracranial lesion was shown in the MRI. THS was diagnosed and the patient's CN 6 palsy recovered quickly after corticosteroid treatment. However, severe anaemia was discovered during admission (Hb=6.0), so the patient was evaluated by profound laboratory tests, which revealed SLE. CONCLUSION: With painful ophthalmoplegia, cavernous sinus syndrome is highly suspected. THS is one of the differential diagnoses for cavernous sinus syndrome. THS is a rare disease, recognized by the National Organization for Rare Disorders, and characterized by inflammatory changes in the cavernous sinus, superior orbital fissure and/or orbital apex under image study. The inflammatory changes are mostly idiopathic, but secondary causes such as sarcoidosis or other autoimmune diseases need to be ruled out. Physicians should be aware of possible underlying conditions, such as immunosuppressed status as in SLE, as the true cause of THS.
Asunto(s)
Seno Cavernoso , Lupus Eritematoso Sistémico , Síndrome de Tolosa-Hunt , Seno Cavernoso/diagnóstico por imagen , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Síndrome de Tolosa-Hunt/diagnóstico , Síndrome de Tolosa-Hunt/etiologíaRESUMEN
OBJECTIVE: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. DESIGN: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. RESULTS: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. CONCLUSION: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. TRIAL REGISTRATION NUMBER: NCT01235689; Results.
Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Análisis Costo-Beneficio , Enfermedad de Crohn/metabolismo , Hospitalización , Humanos , Complejo de Antígeno L1 de Leucocito/metabolismo , Años de Vida Ajustados por Calidad de Vida , Evaluación de Síntomas , Resultado del Tratamiento , Reino UnidoRESUMEN
OBJECTIVES: TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA. METHODS: We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios for infection associated with TNFIs compared with DMARDs, adjusting for potential confounders with high-dimensional propensity scores and time-varying CS use. RESULTS: We identified 2013 DMARD initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days, respectively. We identified 18 and 11 patients with a serious infection in the DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and 2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models, TNFIs were associated with an increased risk of serious bacterial infection compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86). CONCLUSION: Use of TNFIs poses a higher risk of serious infection compared with DMARDs in children with JIA. Our analysis confirms the US Food and Drug Administration warning about TNFI-associated infection in children with JIA.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Juvenil/tratamiento farmacológico , Infecciones Bacterianas/inducido químicamente , Productos Biológicos/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/efectos adversos , Adolescente , Niño , Etanercept/efectos adversos , Femenino , Humanos , Infliximab/efectos adversos , Masculino , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. METHODS: This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. RESULTS: Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. CONCLUSIONS: Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype.
Asunto(s)
Isquemia Encefálica/epidemiología , Hemorragias Intracraneales/epidemiología , Degeneración Macular/epidemiología , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
Liver cancer is the most endemic cancer in a large region of the world. This study investigated the anti-metastatic effects of an extract of Monascus purpureus CWT715 (MP) fermented from sorghum liquor biowaste and its mechanisms of action in highly metastatic human hepatocarcinoma SK-Hep-1 cells. Kinmen sorghum liquor waste was used as the primary nutrient source to produce metabolites (including pigments) of MP. In the presence of 10 µg/mL MP-fermented broth (MFB), the anti-invasive activity increased with increasing fermentation time reaching a maximum at six days of fermentation. Interestingly, MFB also produced maximal pigment content at six days. Treatment for 24 h with MFB (10-100 µg/mL) obtained from fermentation for six days significantly inhibited cell migration and invasion, and these effects were concentration-dependent. MFB also significantly enhanced nm23-H1 protein expression in a concentration-dependent manner, which was highly correlated with migration and invasion. These results suggest that MFB has significant anti-migration and anti-invasion activities and that these effects are associated with the induction of nm23-H1 protein expression.
Asunto(s)
Monascus/química , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/prevención & control , Extractos Vegetales/farmacología , Sorghum/química , Línea Celular Tumoral , Fermentación , HumanosRESUMEN
Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I-III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for MDS/AML risk. Among 56,251 breast cancer cases, 1.2 % developed MDS/AML during median follow-up of 3.2 years. 47.1 % of women received radiation and 14.3 % received chemotherapy. Compared to breast cancer cases treated with surgery alone, those treated with chemotherapy (HR = 1.38, 95 %-CI 0.98-1.93) and chemotherapy/radiation (HR = 1.77, 95 %-CI 1.25-2.51) had increased risk of MDS/AML, but not radiation alone (HR = 1.08, 95 % CI 0.86-1.36). Among chemotherapy regimens and G-CSF, MDS/AML risk was differentially associated with anthracycline/cyclophosphamide-containing regimens (HR = 1.86, 95 %-CI 1.33-2.61) and filgrastim (HR = 1.47, 95 %-CI 1.05-2.06), but not pegfilgrastim (HR = 1.10, 95 %-CI 0.73-1.66). We observed increased MDS/AML risk among older breast cancer survivors treated with anthracycline/cyclophosphamide chemotherapy that was enhanced by G-CSF. Although small, this risk warrants consideration when determining adjuvant chemotherapy and neutropenia prophylaxis for breast cancer patients.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Leucemia Mieloide Aguda/patología , Síndromes Mielodisplásicos/patología , Anciano , Anciano de 80 o más Años , Antraciclinas/efectos adversos , Neoplasias de la Mama/complicaciones , Quimioterapia Adyuvante/efectos adversos , Ciclofosfamida/efectos adversos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Leucemia Mieloide Aguda/inducido químicamente , Síndromes Mielodisplásicos/inducido químicamente , Estadificación de Neoplasias , Polietilenglicoles , Modelos de Riesgos Proporcionales , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversosRESUMEN
AIMS: The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner. METHODS: We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively. RESULTS: The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBMâ vs.â PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs.â PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22). CONCLUSIONS: MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.
Asunto(s)
Antitiroideos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hipertiroidismo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antitiroideos/administración & dosificación , Antitiroideos/uso terapéutico , Carbimazol/administración & dosificación , Carbimazol/efectos adversos , Carbimazol/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Estudios de Cohortes , Bases de Datos Factuales , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Metimazol/administración & dosificación , Metimazol/efectos adversos , Metimazol/uso terapéutico , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Propiltiouracilo/administración & dosificación , Propiltiouracilo/efectos adversos , Propiltiouracilo/uso terapéutico , Estudios Retrospectivos , Taiwán , Adulto JovenRESUMEN
INTRODUCTION: Individuals living with Crohn's disease (CD) experience burdensome symptoms. As such, it is important to measure CD symptom severity in clinical research. The goal of this study was to evaluate the content validity, psychometric performance, and score interpretability of a new patient-reported instrument, the Crohn's Symptom Severity (CSS) questionnaire, among adolescents and adults with moderately to severely active CD. METHODS: Cognitive debriefing interviews (N = 30; n = 20 adults, n = 10 adolescents) were conducted to evaluate the content validity of the CSS. Additionally, the CSS scores were evaluated for reliability and validity using data from a phase 3 randomized clinical trial of risankizumab (NCT03105128; N = 850). Meaningful within-patient change (MWPC) thresholds were estimated using anchor-based methods. RESULTS: All interview participants (n = 30/30, 100.00%) reported the CSS was easy to complete and most participants (n = 28/29, 96.55%) reported that the CSS was relevant to their experience of CD. Among the clinical trial subjects (N = 850) the following was found for the CSS: mostly acceptable item-total correlations (0.26-0.79); weak to moderate inter-item correlations (r = 0.07-0.57), good internal consistency (Cronbach's α = 0.76-0.87); intraclass correlation coefficients ranged from 0.48 to 0.70, not consistently exceeding the acceptable range for test-retest reliability (0.70); acceptable convergent validity and known-groups results; and demonstrated sensitivity to change. Analyses supported an MWPC estimate of 6-11 points. CONCLUSIONS: This study supports use of the CSS for measuring CD symptoms and sleep impact among adolescents and adults aged 16 and older with moderately to severely active CD in clinical research. TRIAL REGISTRATION: NCT03105128 (registration date 4 April 2017).
RESUMEN
INTRODUCTION: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD. METHODS: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up. RESULTS: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab. CONCLUSIONS: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab. TRIAL REGISTRATION: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).
RESUMEN
BACKGROUND AND AIMS: Quality of life in patients with active Crohn's disease may be significantly reduced. We evaluated the effects of upadacitinib induction and maintenance therapy on fatigue, quality of life, and work productivity in the phase 3 trials U-EXCEL, U-EXCEED, and U-ENDURE. METHODS: Clinical responders to upadacitinib 45 mg in U-EXCEL and U-EXCEED induction trials were re-randomized 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance in U-ENDURE. Clinically meaningful improvements in Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Work Productivity and Activity Impairment were evaluated. Percentages of patients achieving clinically meaningful improvements were assessed at induction Weeks 4 and 12 and maintenance Week 52. RESULTS: Analysis included 1021 and 502 patients assessed at induction and maintenance, respectively. In U-EXCEL, greater improvements (all p≤0.001) in IBDQ response (71.0% vs 50.2%), IBDQ remission (44.2% vs 23.7%), and FACIT-Fatigue (42.0% vs 27.0%) were observed in upadacitinib-treated patients versus placebo at Week 4. Improvements in IBDQ response, IBDQ remission, and FACIT-Fatigue were similar or greater at Week 12. Clinically meaningful improvement in overall work impairment (52.1% vs 38.1%, p≤0.05) was demonstrated at Week 12. Similar results were observed in U-EXCEED. Improvements were sustained through 52 weeks of upadacitinib maintenance treatment. CONCLUSIONS: In patients with active Crohn's disease, upadacitinib treatment relative to placebo significantly improved fatigue, quality of life, and work productivity as early as Week 4. These effects were sustained through 52 weeks of maintenance.
RESUMEN
INTRODUCTION: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. METHODS: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). RESULTS: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16. CONCLUSIONS: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422.
Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 12 weeks. The extent of the improvements increased through weeks 46 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis.
RESUMEN
BACKGROUND: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. OBJECTIVE: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. METHODS: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. RESULTS: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. CONCLUSIONS: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018).
Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 12 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis.
Asunto(s)
Dermatitis Atópica , Compuestos Heterocíclicos con 3 Anillos , Inhibidores de las Cinasas Janus , Medición de Resultados Informados por el Paciente , Prurito , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/complicaciones , Masculino , Femenino , Adulto , Adolescente , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Resultado del Tratamiento , Prurito/tratamiento farmacológico , Prurito/etiología , Prurito/diagnóstico , Adulto Joven , Inhibidores de las Cinasas Janus/administración & dosificación , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Persona de Mediana Edad , Método Doble CiegoRESUMEN
Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings. We aimed to estimate the risk of MS in patients with ON using a nationally representative sample. A cohort of 2,741 patients who sought outpatient care for ON in 2000 was identified from Taiwan's National Health Insurance claims. The control group consisted of 27,330 age- and sex-matched subjects randomly selected from all beneficiaries in 2000. The person-year approach with Poisson assumption was used to estimate the incidence rate of MS from 2000 to 2008. The relative risk of outpatient visit or hospitalization for MS was estimated using the Cox proportional hazard model. The incidence rates of MS in the ON and control groups were 25.6 and 0.4, respectively, per 10,000 person-years; these values represent a relative risk estimate of 30.84 (95% confidence interval: 14.48 to 65.73) after the potential confounders were considered. Female or younger patients with ON were associated with a significantly elevated risk of developing MS. This study found that Taiwanese patients with ON are at a substantially high relative risk of developing MS. In addition to patients with ON, female and younger people should also receive intensive neurological care to further reduce their risk of developing MS.
Asunto(s)
Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/etiología , Neuritis Óptica/complicaciones , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: Immune checkpoint inhibitors are rapidly being used in solid and hematologic malignancies, including gynecologic cancers. The high mortality and relapsing rates of advanced gynecologic malignancies remain a challenging issue. This study aimed to identify the predicting factors associated with survival prognosis and disease control in patients with refractory/relapsing (R/R) gynecologic malignancies receiving anti PD-1 therapy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 49 patients diagnosed with R/R gynecologic malignancies between July 2012 and June 2019 in Chang Gung Memorial Hospital, Taiwan. Among the 49 patients, 6 were excluded due to incomplete medical records or not receiving anti PD-1 therapy. The remaining 43 patients were further divided into responsive and non-responsive groups according to disease control for predicting prognostic factor analysis. RESULTS: For the 43 cases, the median age at diagnosis and disease follow-up length were 54 years and 29 months, respectively. Among them, 23 (53%) were categorized into the responsive group, and the remaining 20 (47%) were categorized into the non-responsive group. The mortality rates were 17% and 25% in the responsive and non-responsive groups, respectively. The responsive group had significantly higher absolute lymphocyte count (ALC), higher absolute neutrophil count (ANC) and low platelet to lymphocyte ratio (PLR) than the non-responsive group. A superior long-term survival trend was also observed in the responsive group, but the difference was not statistically significant. CONCLUSIONS: This study reinforced the hypothesis that high ALC, high ANC and low PLR are associated with superior disease control in patients with R/R gynecologic malignancies receiving anti PD-1 therapy.
Asunto(s)
Neoplasias de los Genitales Femeninos , Neutrófilos , Humanos , Femenino , Estudios Retrospectivos , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/patología , Recurrencia Local de Neoplasia/patología , Linfocitos , Recuento de Linfocitos , PronósticoRESUMEN
INTRODUCTION: Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC. METHODS: Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE®, Embase®, and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]). RESULTS: Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies (n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks. CONCLUSION: Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation. PROSPERO REGISTRATION: CRD42021289251.