RESUMEN
Clinically meaningful benefits in the signs, symptoms, and impacts of #PKDeficiency as assessed by disease-specific patient-reported outcome measures were observed in mitapivat-treated adult patients in two phase 3 clinical trials.
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Medición de Resultados Informados por el Paciente , Piruvato Quinasa , Errores Innatos del Metabolismo del Piruvato , Humanos , Piruvato Quinasa/deficiencia , Adulto , Masculino , Femenino , Persona de Mediana Edad , Anemia Hemolítica Congénita no Esferocítica , Resultado del TratamientoRESUMEN
Real-world studies of pyruvate kinase (PK) deficiency and estimates of mortality are lacking. This retrospective observational study aimed to identify patients with PK deficiency and compare their overall survival (OS) to that of a matched cohort without PK deficiency. Patients with ≥1 diagnosis code related to PK deficiency were selected from the US Veterans Health Administration (VHA) database (01/1995-07/2019); patients with a physician-documented diagnosis were included (PK deficiency cohort; index: date of first diagnosis code related to PK deficiency). Patients in the PK deficiency cohort were matched 1:5 to patients from the general VHA population (non-PK deficiency cohort; index: random visit date during match's index year). OS from index was compared between the two cohorts. Eighteen patients in the PK deficiency cohort were matched to 90 individuals in the non-PK deficiency cohort (both cohorts: mean age 57 years, 94% males; median follow-up 6.0 and 8.0 years, respectively). At follow-up, patients in the non-PK deficiency cohort had significantly longer OS than the PK deficiency cohort (median OS: 17.1 vs. 10.9 years; hazard ratio: 2.3; p = 0.0306). During their first-year post-index, 75% and 40% of the PK deficiency cohort had laboratory-confirmed anemia and iron overload, respectively. Among patients who died, cause of death was highly heterogeneous. These results highlight the increased risk of mortality and substantial clinical burden among patients with PK deficiency. While the intrinsic characteristics of the VHA database may limit the generalizability of the results, this is the first real-world study to characterize mortality in patients with PK deficiency.
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Anemia Hemolítica Congénita no Esferocítica , Errores Innatos del Metabolismo del Piruvato , Veteranos , Masculino , Humanos , Persona de Mediana Edad , Femenino , Piruvato Quinasa , Anemia Hemolítica Congénita no Esferocítica/diagnóstico , Anemia Hemolítica Congénita no Esferocítica/etiología , Errores Innatos del Metabolismo del Piruvato/diagnóstico , Errores Innatos del Metabolismo del Piruvato/complicacionesRESUMEN
BACKGROUND: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220). METHODS: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline. Completion rates and baseline response distributions were characterized using descriptive statistics. Item response modelling was used to inform a weighted scoring system. Reliability was assessed by internal consistency and test-retest reliability; and validity by convergent and known-groups analyses. RESULTS: Of the 80 adults enrolled, baseline data were available for 77 (96.3%) and 78 (97.5%) patients for the PKDD and PKDIA, respectively. Item responses skewed right, indicating that mean values exceeded median values, especially for items utilizing a 0-10 numeric scale, which were subsequently recoded to a 0-4 scale; 4 items were removed from the PKDIA due to redundancy or low relevance to the trial population. Both the PKDD and PKDIA demonstrated high internal consistency (McDonald's coefficient ω = 0.86 and 0.90, respectively), test-retest reliability (intra-class coefficients of 0.94 and 0.87, respectively), and convergent validity with other PROs (linear correlation coefficients [|r|] between 0.30-0.73 and 0.50-0.82, respectively). CONCLUSIONS: The findings provide evidence of validity and reliability for the PKDD and PKDIA, the first disease-specific PRO measures for PK deficiency, and can therefore increase understanding of, and more accurately capture, the wider impact of PK deficiency on health-related quality of life. Trial registration ClinicalTrials.gov, NCT03548220. Registered June 07, 2018; https://www. CLINICALTRIALS: gov/ct2/show/NCT03548220 .
Pyruvate kinase (PK) deficiency is a rare genetic blood disorder with a wide range of signs and symptoms that may have a negative impact on patients' quality of life. Patient-reported outcome (PRO) instruments are tools that assess how a disease affects a patient from the patient's perspective. These instruments must go through a validation process to make sure they truly capture the patient's experience with their condition or its treatment. This study aimed to validate two new PRO instruments in adult patients enrolled in the ACTIVATE clinical trial (NCT03548220), where patients with PK deficiency received the drug mitapivat or a placebo. These two new PRO instruments are the first to be developed specifically for PK deficiency: the PK Deficiency Diary (PKDD), a daily diary that asks 7 questions to measure the core signs and symptoms of PK deficiency, and the PK Deficiency Impact Assessment (PKDIA), a weekly questionnaire with 12 questions to assess the impact of PK deficiency on a patient's life. The results of this study showed that the PKDD and PKDIA properly and reliably measured the signs, symptoms, and impacts of PK deficiency that they aimed to capture. These findings indicate that the PKDD and PKDIA are the first validated PROs specifically for PK deficiency and can help improve the understanding of the impact of PK deficiency on patients' quality of life.
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Piruvato Quinasa , Calidad de Vida , Adulto , Humanos , Psicometría , Enfermedades Raras , Reproducibilidad de los ResultadosRESUMEN
This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha- and beta-thalassemia. Embase, MEDLINE, and the Cochrane Library were searched for observational studies published January 1, 2000, to September 21, 2021. Of 2093 unique records identified, 69 studies reported across 70 publications met eligibility criteria, including 6 records identified from bibliography searches. Thalassemia prevalence estimates varied across countries and even within countries. Across 23 population-based studies reporting clinically significant alpha-thalassemia (e.g., hemoglobin H disease and hemoglobin Bart's hydrops fetalis) and/or beta-thalassemia (beta-thalassemia intermedia, major, and/or hemoglobin E/beta-thalassemia), prevalence estimates per 100 000 people ranged from 0.2 in Spain (over 2014-2017) to 27.2 in Greece (2010-2015) for combined beta- plus alpha-thalassemia; from 0.03 in Spain (2014-2017) to 4.5 in Malaysia (2007-2018) for alpha-thalassemia; and from 0.2 in Spain (2014-2017) to 35.7 to 49.6 in Iraq (2003-2018) for beta-thalassemia. Overall, the estimated prevalence of thalassemia followed the predicted pattern of being higher in the Middle East, Asia, and Mediterranean than in Europe or North America. However, population-based prevalence estimates were not found for many countries, and there was heterogeneity in case definitions, diagnostic methodology, type of thalassemia reported, and details on transfusion requirements. Limited population-based birth prevalence data were found. Twenty-seven studies reported thalassemia prevalence from non-population-based samples. Results from such studies likely do not have countrywide generalizability as they tended to be from highly specific groups. To fully understand the global prevalence of thalassemia, up-to-date, population-based epidemiological data are needed for many countries.
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Hemoglobinas Anormales , Talasemia alfa , Talasemia beta , Embarazo , Femenino , Humanos , Talasemia alfa/epidemiología , Talasemia beta/epidemiología , Diagnóstico Prenatal/métodos , Hidropesía Fetal/diagnóstico , AsiaRESUMEN
BACKGROUND: Mitapivat, an oral activator of pyruvate kinase (PK) in red blood cells (RBCs), has shown significant improvements in haemoglobin and haemolysis among patients with pyruvate kinase deficiency who were not receiving regular transfusions. We aimed to evaluate the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency receiving regular transfusions. METHODS: ACTIVATE-T was an open-label, single-arm, phase 3 trial conducted in 20 centres across Europe, North America, and Asia. Eligible participants were adults (aged ≥18 years) with a clinical laboratory confirmation of pyruvate kinase deficiency receiving regular transfusions (at least six episodes in the previous year). Participants received oral mitapivat during a 16-week dose-optimisation period (5 mg, 20 mg, 50 mg twice daily) and 24-week fixed-dose period. The primary endpoint was a reduction in transfusion burden (≥33% reduction in number of RBC units transfused during the fixed-dose period, compared with the participant's individual historical transfusion burden, standardised to 24 weeks). Efficacy and safety were assessed in all participants who received at least one dose of mitapivat. This trial is registered with ClinicalTrials.gov, NCT03559699, and is complete. FINDINGS: Between June 26, 2018, and Feb 4, 2020, 27 participants (20 [74%] female and seven [26%] male; 20 [74%] White, three [11%] Asian, and four [15%] not reported) were enrolled and received at least one dose of mitapivat. Median duration of exposure to mitapivat was 40·3 weeks (IQR 40·0-41·3). A reduction in transfusion burden by at least 33% was found in ten (37%) participants (95% CI 19-58; p=0·0002). The most common treatment-emergent adverse events were increase in alanine aminotransferase (ten [37%] participants), headache (ten [37%]), increase in aspartate aminotransferase (five [19%]), fatigue (five [19%]), and nausea (five [19%]). Two grade 3 treatment-emergent adverse events were related to study treatment: joint swelling (one participant [4%]) and an increase in aspartate aminotransferase (one participant [4%]). Three participants had serious treatment-emergent adverse events, none related to the study treatment: increased blood triglycerides, ovarian cyst, and renal colic (each in one participant [4%]). No treatment-related deaths were observed. INTERPRETATION: Mitapivat represents a novel therapy that can reduce transfusion burden in some adults with pyruvate kinase deficiency receiving regular transfusions, and is the first disease-modifying agent approved in this disease. FUNDING: Agios Pharmaceuticals.
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Hemoglobinas , Piruvato Quinasa , Adolescente , Adulto , Alanina Transaminasa , Anemia Hemolítica Congénita no Esferocítica , Aspartato Aminotransferasas , Femenino , Humanos , Masculino , Preparaciones Farmacéuticas , Piperazinas , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato , Quinolinas , Resultado del Tratamiento , TriglicéridosRESUMEN
BACKGROUND: Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in patients with pyruvate kinase deficiency. METHODS: In this global, phase 3, randomized, placebo-controlled trial, we evaluated the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency who were not receiving regular red-cell transfusions. The patients were assigned to receive either mitapivat (5 mg twice daily, with potential escalation to 20 or 50 mg twice daily) or placebo for 24 weeks. The primary end point was a hemoglobin response (an increase from baseline of ≥1.5 g per deciliter in the hemoglobin level) that was sustained at two or more scheduled assessments at weeks 16, 20, and 24. Secondary efficacy end points were the average change from baseline in the hemoglobin level, markers of hemolysis and hematopoiesis, and the change from baseline at week 24 in two pyruvate kinase deficiency-specific patient-reported outcome measures. RESULTS: Sixteen of the 40 patients (40%) in the mitapivat group had a hemoglobin response, as compared with none of the 40 patients in the placebo group (adjusted difference, 39.3 percentage points; 95% confidence interval, 24.1 to 54.6; two-sided P<0.001). Patients who received mitapivat had a greater response than those who received placebo with respect to each secondary end point, including the average change from baseline in the hemoglobin level. The most common adverse events were nausea (in 7 patients [18%] in the mitapivat group and 9 patients [23%] in the placebo group) and headache (in 6 patients [15%] and 13 patients [33%], respectively). Adverse events of grade 3 or higher occurred in 10 patients (25%) who received mitapivat and 5 patients (13%) who received placebo. CONCLUSIONS: In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported outcomes. No new safety signals were identified in the patients who received mitapivat. (Funded by Agios Pharmaceuticals; ACTIVATE ClinicalTrials.gov number, NCT03548220.).
Asunto(s)
Piperazinas , Piruvato Quinasa , Quinolinas , Adulto , Anemia Hemolítica Congénita no Esferocítica/tratamiento farmacológico , Método Doble Ciego , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Piperazinas/farmacología , Piperazinas/uso terapéutico , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato/tratamiento farmacológico , Quinolinas/farmacología , Quinolinas/uso terapéuticoRESUMEN
BACKGROUND: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION: NCT01578499.
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Brentuximab Vedotina/uso terapéutico , Linfoma Cutáneo de Células T/tratamiento farmacológico , Calidad de Vida , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Linfoma Cutáneo de Células T/epidemiología , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/psicología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/psicología , Medición de Resultados Informados por el Paciente , Psicometría/métodos , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/psicología , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Objectives: To summarize the impact of relapsed/refractory primary cutaneous T-cell lymphomas (CTCL) on quality of life (QoL) and the efficacy of available treatments in two systematic reviews (SRs).Methods: Searches were performed on 16 January 2018 and 23 January 2018, respectively, in Medline, Medline in process, the Cochrane database, and EconLit. Studies reporting QoL outcomes in adults with CTCL or treatment efficacy in relapsed/refractory CTCL were included.Results: Based on 15 QoL studies, CTCL symptoms/complications negatively affect patients' physical, emotional, and social functioning. Skin problems pose considerable symptom burden, while advanced disease stage is associated with poorer QoL. CTCL negatively affects caregivers, primarily through family dynamics and relationships. The clinical efficacy SR included 72 publications covering 23 therapies. Overall response rate (ORR) ranged from 14% (belinostat) to 95% (total skin electron beam therapy). ORRs >50% were reported for several therapies including brentuximab vedotin (50-78%) and bexarotene (39-86%). Over half (13 of 23 therapies) had ORRs <30%. Median progression-free survival varied between treatments (3.5-116.4 months) and was >20 months for brentuximab vedotin and alemtuzumab.Conclusion: CTCL negatively affects patients' and caregivers' QoL. A considerable proportion of patients have no response or no sustainable response to current treatments.
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Antineoplásicos/uso terapéutico , Costo de Enfermedad , Linfoma Cutáneo de Células T/mortalidad , Linfoma Cutáneo de Células T/terapia , Calidad de Vida , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Antineoplásicos/efectos adversos , Supervivencia sin Enfermedad , Humanos , Tasa de SupervivenciaRESUMEN
PURPOSE: Multiple new regimens are available for the treatment of relapsed/refractory multiple myeloma (RRMM). In this context, it is increasingly important to understand the differential costs of regimens used to treat RRMM. METHODS: A treatment journey for RRMM during a 12-month period of therapy was developed to reflect real-world clinical practice based on current treatment guidelines and input from hematologists/oncologists. The journey incorporated prescreening visits, laboratory tests, regimen-specific premedication, treatment-related costs, medical costs, and indirect costs. A cost model was constructed from the standard RRMM treatment pathway to compare overall, direct, and indirect costs across therapies over a 12-month period from initiation of second-line therapy and to determine cost offsets (incremental costs) associated with use of ixazomib-based therapy versus comparator regimens. According to the clinical input, the standard pathway was modified for patients with high unmet need to determine specific cost offsets in these subgroups. FINDINGS: Total costs ranged from $93,683 for bortezomib-cyclophosphamide-dexamethasone to $315,296 for daratumumab-bortezomib-dexamethasone. Drug cost comprised the highest proportion (83%-98%) of total costs of second-line therapy across regimens, which were generally highest for regimens based on recently approved agents. Indirect costs were higher for regimens that required more frequent or longer durations of drug administration, and lower for all-oral regimens. Costs were reduced among frail patients because of the use of adjusted dosing, whereas indirect costs were increased for regimens that required a greater number of clinic visits among patients with barriers to physician access. IMPLICATIONS: Cost model analyses highlight the differential direct and indirect costs associated with multiple regimens for the treatment of RRMM, including many recent new regimens. The results indicate the lower treatment burden and indirect costs associated with administering all-oral regimens compared with regimens that require frequent and/or lengthy subcutaneous or intravenous infusions. Understanding comparative costs associated with the treatment journeys of different patients with RRMM may help inform payer and patient therapeutic choices.
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Protocolos de Quimioterapia Combinada Antineoplásica/economía , Mieloma Múltiple/economía , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/economía , Antineoplásicos/administración & dosificación , Antineoplásicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bortezomib/administración & dosificación , Bortezomib/economía , Ciclofosfamida/administración & dosificación , Ciclofosfamida/economía , Dexametasona/administración & dosificación , Dexametasona/economía , Costos de la Atención en Salud , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/economía , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
First-line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography-driven strategies and ABVD or BEACOPP variants incorporating the antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under investigation in advanced-stage patients. The present study aimed to elicit preferences for attributes associated with ABVD, BEACOPPescalated and BV-AVD (BV, adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross-sectional online discrete choice experiments were administered to HL patients (n = 381) and haematologists/oncologists (n = 357) in France, Germany and the United Kingdom. Included attributes were progression-free survival (PFS), overall survival (OS), and the risk of neuropathy, lung damage, infertility and hospitalisation due to adverse events. Whereas 5-year PFS and OS were the most important treatment attributes to patients, the relative importance of each attribute and preference weights for each level varied among physicians according to the description of the hypothetical patient for whom treatment was recommended. PFS and OS most strongly influenced physicians' recommendations when considering young female patients who did not want children or young male patients. Infertility was more important to physicians' treatment decision than PFS when considering young women with unknown fertility preferences, whereas hospitalisations due to adverse events played the largest role in treatment decisions for older patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Prioridad del Paciente , Pautas de la Práctica en Medicina , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Estudios Transversales , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Francia/epidemiología , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Tasa de Supervivencia , Reino Unido/epidemiología , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
This retrospective study compared effectiveness of (brentuximab vedotin) BV to other chemotherapies in patients with rrHL following an autologous stem cell transplant (ASCT). Data originated from a medical chart review of patients treated in real-world clinical settings at 50 sites in the United Kingdom and Germany. Inverse probability of treatment weights based on propensity scores were used to adjust for differences in baseline characteristics between treatment groups. Among 312 rrHL patients included, 196 received BV and 116 received physicians' choice chemotherapy. Median PFS was significantly longer (27.0 months vs. 13.4 months; p = .0144) and 12-month OS survival greater (78.1% vs. 65.9%; p = .0129) with BV compared to chemotherapy. Documented adverse events included leukopenia (12.8%) and peripheral neuropathy (8.7%) for BV and leukopenia (12.1%), anemia (5.2%) and diarrhea (5.2%) for chemotherapy. In this real-world study, rrHL patients treated for relapse after ASCT with BV had longer median PFS and 12-month OS than patients receiving chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Inmunoconjugados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina , Resistencia a Antineoplásicos , Femenino , Alemania , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Masculino , Cuidados Posoperatorios , Recurrencia , Retratamiento , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Reino UnidoRESUMEN
The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18-6.07 for patients with ≥2 risk factors, and 2.98-5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3-8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.
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Antineoplásicos Inmunológicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Inmunoconjugados/uso terapéutico , Neoplasia Residual/patología , Adolescente , Adulto , Anciano , Brentuximab Vedotina , Terapia Combinada , Quimioterapia de Consolidación , Progresión de la Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate licensed for the treatment of relapsed/refractory Hodgkin lymphoma (rrHL) following autologous stem cell transplant (ASCT) or at least two prior therapies when ASCT or multiagent chemotherapy is not an option. The objective of this study was to describe real-world outcomes with BV in patients with rrHL considered ASCT ineligible or who refuse ASCT. METHODS: This was a retrospective medical chart review study that enrolled patients ≥18 years old who were initially diagnosed with HL between January 1, 2008 and June 30, 2014, considered ASCT ineligible, and treated in routine care with BV for progressive disease after multidrug chemotherapy regimens. Clinical outcomes included best response to treatment, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: A total of 136 patients were included, with a median age of 70 years at initial HL diagnosis. The most common reasons for ASCT ineligibility were comorbidities (74%) and age (57%). Overall response rate was 74%, and PFS and OS were 15.1 and 17.8 months, respectively. Peripheral neuropathy was observed in 9.6% of patients. CONCLUSION: The results of this study provide real-world evidence on the feasibility and effectiveness of BV in elderly or frail ASCT-ineligible patients with rrHL in a real-world setting.
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Antineoplásicos/uso terapéutico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Inmunoconjugados/uso terapéutico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Brentuximab Vedotina , Resistencia a Antineoplásicos , Femenino , Alemania , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Retratamiento , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Reino UnidoRESUMEN
BACKGROUND: Rosacea is a condition more common in women than in men, and in people aged ≥30 years than in younger patients. Adverse events associated with the use of topical medications for rosacea may lead to a lack of treatment adherence. Previous studies have reported low treatment adherence rates among patients with rosacea. OBJECTIVE: To describe the rate of treatment discontinuation resulting from adverse events and the associated healthcare costs among patients with rosacea who are receiving a topical medication. METHODS: We conducted a retrospective cohort study of patients diagnosed with rosacea based on International Classification of Diseases, Ninth Revision, Clinical Modification code 695.3 who were newly initiating topical treatment with metronidazole, azelaic acid, sodium sulfacetamide/sulfur, or benzoyl peroxide between January 1, 2009, and September 30, 2013. Patients were identified from the MarketScan Commercial Claims and Encounters database and the Medicare Supplemental database and had to be aged ≥30 years, have continuous coverage with medical and pharmacy benefits ≥12 months before treatment and ≥3 months after treatment inititation, and have no evidence of oral antibiotic use or ocular rosacea during the study period. The 3-month period immediately after the index date (ie, first topical rosacea treatment) was defined as the postindex period and was used to evaluate the outcome measures, which included the rate of adverse events, treatment patterns, and healthcare costs. RESULTS: The final cohort included 49,351 patients, with a mean age of 54 years, and 74.5% of the patients were female. Metronidazole was the most common (72.7%) treatment, followed by azelaic acid (21.7%), sodium sulfacetamide/sulfur (3.4%), and benzoyl peroxide (2.2%). A total of 6270 (12.7%) patients had a coded adverse event, of whom 199 (3.2%) continued treatment despite the adverse event, 466 (7.4%) switched to another treatment within 8.8 days, and 5605 (89.4%) discontinued therapy within 31.1 days. Patients with adverse events incurred, on average, a cost of $325 (medical, $143; pharmacy, $182) in rosacea-related costs; patients without adverse events incurred, on average, a cost of $172 (medical, $14; pharmacy, $157) in rosacea-related costs. CONCLUSIONS: The majority of adverse events associated with current topical drugs for rosacea resulted in treatment switch or discontinuation. Drugs with a different mechanism of action or new formulations of existing drugs may provide additional treatment options for patients and may lead to improved adherence and better symptom control.
RESUMEN
BACKGROUND: Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. METHODS: In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. FINDINGS: Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. INTERPRETATION: Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. FUNDING: Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.
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Linfoma Cutáneo de Células T , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotina , Humanos , Inmunoconjugados , Recurrencia Local de NeoplasiaRESUMEN
AIM: To describe treatments and cost of care for prostate cancer (PCa) in hospital-based outpatient and inpatient settings. METHODS: Hospital encounters associated with PCa (ICD-9 codes 185, 233.4) and PCa-related treatment in a hospital claims database were included. RESULTS: There were 211,440 encounters for PCa between January 2006 and December 2010 (88,151 inpatient and 123,289 outpatient). Average cost per inpatient stay was US$12,286 versus US$4364 per outpatient visit. Most common treatment during an inpatient stay and outpatient visit was surgery (57%) and radiation (76%), respectively. A total of 80% of outpatient visits and 69.9% inpatient stays were associated with a single treatment; remaining encounters were associated with ≥2 treatments. CONCLUSION: Costs are consistent with previous estimates; however, multimodal therapy is an emerging trend that may be related to greater costs in the future which may also be a challenge for hospital decision makers.
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Costos de la Atención en Salud , Pacientes Internos , Pacientes Ambulatorios , Neoplasias de la Próstata/epidemiología , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Hospitalización/economía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Since 2010, several new treatments for prostate cancer (PCa), which have entered the US market, are poised to have an impact on treatment approaches; however, there is a paucity of evidence with respect to treatment patterns and costs. As new treatment patterns emerge, it will be imperative to understand treatment patterns and costs of care prior to the advent of novel treatments. OBJECTIVE: As the PCa treatment landscape is evolving, this study sought to compare the hospital-based utilization and costs in two cohorts of patients with PCa: patients with bone metastases (w/BM) and patients without bone metastases (w/oBM). Comparisons were also made for patients with inpatient versus outpatient encounters. METHODS: Patients in the Premier Perspective Database, a US hospital database, between January 2006 and December 2010, treated in an inpatient or outpatient setting for PCa (International Classification of Diseases, 9th Revision [ICD-9] diagnosis codes 185, 233.4) were included. Patients were required to be ≥40 years of age with no additional cancers. Patients were put into cohorts on the basis of the presence of bone metastases (ICD-9 code 198.5 or use of zoledronic acid or pamidronate disodium). Utilization of PCa-related treatments was compared, controlling for age, race, hospital type, payer type, bed size, and admission source and type. Differences in treatments were assessed utilizing logistic regression, while differences in costs were analyzed using gamma-distributed generalized linear models with a log-link function. All costs are reported in US$ 2010. RESULTS: There were 23,747 hospitalizations for men w/BM (13,716 inpatient; 10,031 outpatient) and 187,708 hospitalizations (74,435 inpatient; 113,258 outpatient) for men w/oBM. The mean length of stay for men w/BM was 4 days compared with 2 days for men w/oBM (P < 0.0001). Overall, the mean cost per encounter was US$9,728 in men with w/BM and US$7,405 in men w/oBM (P = 0.0006). For inpatient stays, the mean cost per encounter was US$14,145 for men w/BM and US$11,944 for men w/oBM. For outpatient visits, the mean cost per encounter was US$3,688 for men w/BM and US$4,422 for men w/oBM. Men w/BM received hormone therapy (44.3%) and secondary hormone therapy (46.4%) most often, while men w/oBM received radiation (48.8%) and surgery (31.9%) most often. CONCLUSION: Costs and utilization of PCa-related treatments vary on the basis of the presence of metastases and treatment setting (inpatient vs. outpatient).
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Atención Ambulatoria/economía , Neoplasias Óseas/secundario , Costos de la Atención en Salud , Hospitalización/economía , Neoplasias de la Próstata/economía , Neoplasias de la Próstata/terapia , Asignación de Recursos/economía , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/economía , Neoplasias Óseas/terapia , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Asignación de Recursos/organización & administración , Asignación de Recursos/estadística & datos numéricosRESUMEN
BACKGROUND: A patient-reported outcome (PRO) is a subjective report that comes from a patient without interpretation by a clinician. Because of the increasingly significant role of PROs in the development and evaluation of new medicines, the US Food and Drug Administration (FDA) issued a formal guidance to describe how PRO instruments will be reviewed and evaluated with respect to claims in approved medical product labeling. Meanwhile, PROs continue to appear in oncology clinical trials more frequently; however, it is unclear how payers and policymakers can use PRO data in the context of decision-making for cancer treatments. OBJECTIVE: The objective of this article is to discuss the challenges and opportunities of incorporating oncology-related PRO data into payer decision-making. DISCUSSION: Payer concerns with PRO instruments are often related to issues regarding measurement, relevance, quality, and interpretability of PROs. Payers may dismiss PROs that do not independently predict improved outcomes. The FDA guidance released in 2009 demonstrates, as evidenced by the case of ruxolitinib, how PRO questionnaires can be generated in a relevant, trustworthy, and meaningful way, which provides an opportunity for payers and policy decision makers to focus on how to use PRO data in their decision-making. This is particularly relevant in oncology, where a recent and sizable number of clinical trials include PRO measures. CONCLUSION: As an increasing number of oncology medications enter the market with product labeling claims that contain PRO data, payers will need to better familiarize themselves with the opportunities associated with PRO questionnaires when making coverage decisions. PRO measures will continue to provide valuable information regarding the risk-benefit profile of novel agents. As such, PRO measures may provide evidence that should be considered in payers' decisions and discussions; however, the formal role of PROs and the pertinence of PROs in decision-making has yet to be understood.