Assuntos
Alopecia em Áreas , Análise Custo-Benefício , Medicamentos Genéricos , Piperidinas , Pirimidinas , Pirróis , Humanos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/economia , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/economia , Pirimidinas/economia , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Medicamentos Genéricos/economia , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/uso terapêutico , Feminino , Masculino , Adulto , Resultado do Tratamento , Pirróis/economia , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/uso terapêutico , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: The study aimed to assess the effectiveness of Imatinib in chronic myeloid leukaemia (CML) in our hospital population. In addition to identify which brand of imatinib (Gleevec/Veenat) is cost effective for CML patients and to assess the possible adverse drug reactions during the treatment for chronic myeloid leukaemia. METHODS: A non-interventional (observational), both retrospective and prospective study was carried out in the department of Medical Oncology and Haematology of our hospital. A total of 152 patients were enrolled in the study. Patients who satisfied the inclusion and exclusion criteria were selected for the study. RESULTS: Evaluation of baseline characteristics of study population (n = 152) showed predominance of males (65.1%). The mean age was 49.80 ± 16.561 years. The overall clinical outcome of the sample population, BCR ABL value responses during 3,6 and 12 months are the main indicators for the prediction of outcome in CML -CP patients. Using Independent sample t test, it was found that the difference in response to Imatinib therapy during 3,6 & 12 months were statistically significant and showed a statistically significant difference between the good and adverse outcome (p < 0.001). CONCLUSION: Our study concluded that Imatinib showed a benefit in treating the condition without any life-threatening adverse events and also the drug exhibits a complete haematological and optimal response based on European Leukaemia Net criteria during the period of study. From which, it can be concluded that imatinib appears to be a safe and well-tolerated treatment for the chronic-phase chronic myeloid leukaemia population.
Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Mesilato de Imatinib/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Estudos Prospectivos , Pirimidinas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Antineoplásicos/efeitos adversos , Resultado do Tratamento , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
BACKGROUND: The burden of chronic myeloid leukaemia (CML) is increasing due to longer patient survival, better life expectancy of the general population, and increasing drug prices. Funding is one of the main concerns in the choice of CML medication used worldwide; thus, patient assistance programmes were introduced to ensure accessibility to affordable treatment. In this study, we evaluated CML drug distribution inequality in Malaysia through patient assistance programmes, using pharmaco-economics methods to evaluate CML treatment from the care provider's perspective. METHODS: Patients with CML were recruited from outpatient haematological clinics at the national centre of intervention and referral for haematological conditions and a public teaching hospital. The health-related quality of life or utility scores were derived using the EuroQol EQ-5D-5L questionnaire. Costing data were obtained from the Ministry of Health Malaysia Casemix MalaysianDRG. Imatinib and nilotinib drug costs were obtained from the administration of the participating hospitals and pharmaceutical company. RESULTS: Of the 221 respondents in this study, 68.8% were imatinib users. The total care provider cost for CML treatment was USD23,014.40 for imatinib and USD43,442.69 for nilotinib. The governmental financial assistance programme reduced the total care provider cost to USD13,693.51 for imatinib and USD19,193.45 for nilotinib. The quality-adjusted life years (QALYs) were 17.87 and 20.91 per imatinib and nilotinib user, respectively. Nilotinib had a higher drug cost than imatinib, yet its users had better life expectancy, utility score, and QALYs. Imatinib yielded the lowest cost per QALYs at USD766.29. CONCLUSION: Overall, imatinib is more cost-effective than nilotinib for treating CML in Malaysia from the care provider's perspective. The findings demonstrate the importance of cancer drug funding assistance for ensuring that the appropriate treatments are accessible and affordable and that patients with cancer use and benefit from such patient assistance programmes. To establish effective health expenditure, drug distribution inequality should be addressed.
Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Mesilato de Imatinib/uso terapêutico , Dasatinibe/uso terapêutico , Análise Custo-Benefício , Qualidade de Vida , Malásia/epidemiologia , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pirimidinas/efeitos adversos , Doença Crônica , Uso de MedicamentosRESUMO
Background: Although nilotinib hepatotoxicity can cause severe clinical conditions and may alter treatment plans, risk factors affecting nilotinib-induced hepatotoxicity have not been investigated. This study aimed to elucidate the factors affecting nilotinib-induced hepatotoxicity. Methods: This retrospective cohort study was performed on patients using nilotinib from July of 2015 to June of 2020. We estimated the odds ratio and adjusted odds ratio from univariate and multivariate analyses, respectively. Several machine learning models were developed to predict risk factors of hepatotoxicity occurrence. The area under the curve (AUC) was analyzed to assess clinical performance. Results: Among 353 patients, the rate of patients with grade I or higher hepatotoxicity after nilotinib administration was 40.8%. Male patients and patients who received nilotinib at a dose of ≥300 mg had a 2.3-fold and a 3.5-fold increased risk for hepatotoxicity compared to female patients and compared with those who received <300 mg, respectively. H2 blocker use decreased hepatotoxicity by 11.6-fold. The area under the curve (AUC) values of machine learning methods ranged between 0.61-0.65 in this study. Conclusion: This study suggests that the use of H2 blockers was a reduced risk of nilotinib-induced hepatotoxicity, whereas male gender and a high dose were associated with increased hepatotoxicity.
Assuntos
Fígado/efeitos dos fármacos , Aprendizado de Máquina , Pirimidinas/efeitos adversos , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Área Sob a Curva , Doença Hepática Induzida por Substâncias e Drogas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Estudos Retrospectivos , Risco , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: To evaluate the cost-effectiveness of tofacitinib versus other treatment options currently available for the management of adult patients with moderate-to-severe ulcerative colitis, who have had an inadequate response, loss of response, or were intolerant to conventional therapy or a biologic agent, in Greece. METHODS: A Markov model was adapted for projecting lifetime costs and outcomes, for a cohort of patients with moderate-to-severe ulcerative colitis from a Greek payer perspective. Patients entered the model in the active ulcerative colitis state and transitioned to a remission or response state or they underwent colectomy. Following an initial 8-week induction treatment period, patients received maintenance therapy until loss of response. Nonresponders could switch to up to two subsequent biologic lines. Clinical efficacy, adverse event rates and utilities derived from OCTAVE trials and a network-meta-analysis (NMA), while adverse event-related disutilities were obtained from the literature. Information on treatment pathways and resource use was provided by an advisory board due to a lack of local data. Unit costs derived from official national sources (, 2018). RESULTS: Over a life-time horizon, treating moderate-to-severe active ulcerative colitis with tofacitinib resulted in additional quality-adjusted life-years (QALYs) and lower total costs compared to vedolizumab (0.018; 6408), infliximab (biosimilar) (0.009; 3031), golimumab (0.042; 1988) and infliximab (originator) (0.009; 6724). Hence, tofacitinib was estimated to be dominant over all comparators. CONCLUSION: The results of the analysis suggest that in the Greek setting, tofacitinib could be considered a cost-effective (dominant) treatment option for the treatment of patients with moderate-to-severe active ulcerative colitis.
Assuntos
Colite Ulcerativa , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Análise Custo-Benefício , Grécia , Humanos , Piperidinas , Pirimidinas/efeitos adversosRESUMO
BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. METHODS: Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. RESULTS: In the Induction Cohort [Nâ =â 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [Nâ =â 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [Nâ =â 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. CONCLUSIONS: During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.
Assuntos
Colite Ulcerativa , Herpes Zoster , Hospedeiro Imunocomprometido/efeitos dos fármacos , Infecções , Infecções Oportunistas , Piperidinas , Pirimidinas , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/imunologia , Relação Dose-Resposta a Droga , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/epidemiologia , Humanos , Incidência , Infecções/diagnóstico , Infecções/epidemiologia , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/efeitos adversos , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/epidemiologia , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de DoençaRESUMO
The introduction of novel, small-molecule Janus kinase inhibitors namely tofacitinib, baricitinib and upadacitinib has provided an alternative treatment option for patients with rheumatoid arthritis outside of traditional drugs and expensive biologics. This review aimed to critically assess the drug-drug interaction potential of tofacitinib, baricitinib and upadacitinib and provide a balanced perspective for choosing the most appropriate Janus kinase inhibitor based on the needs of patients with rheumatoid arthritis including co-medications and renal/hepatic impairment status. Based on the critical assessment, all three approved Janus kinase inhibitors generally provide a favourable opportunity for co-prescription with a plethora of drugs. While cytochrome P450 3A4-related inhibition or induction altered the exposures (area under the curve) of tofacitinib and upadacitinib, it did not impact the exposure of baricitinib. Transporter drug-drug interaction studies revealed that the disposition of baricitinib was altered with certain transporter inhibitors as compared with either tofacitinib or upadacitinib. Adjustment of tofacitinib or baricitinib dosages but not that of upadacitinib is required with the progression of renal impairment from a mild to a severe condition. While the dosage of tofacitinib needs to be adjusted for patients with moderate hepatic impairment status, it is not the case for either baricitinib or upadacitinib. Assessment of the drug-drug interaction potential suggests that tofacitinib, baricitinib and upadacitinib generally show a favourable disposition with no perpetrator activity; however, as victim drugs, they show subtle pharmacokinetic differences that may be considered during polypharmacy. Moreover, careful choice of the three drugs could be made in patients with rheumatoid arthritis with varying degrees of renal/hepatic impairments.
Assuntos
Antirreumáticos/efeitos adversos , Azetidinas/efeitos adversos , Interações Medicamentosas , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Janus Quinases/antagonistas & inibidores , Farmacocinética , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Animais , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapêutico , Azetidinas/farmacocinética , Azetidinas/toxicidade , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Piperidinas/farmacocinética , Piperidinas/toxicidade , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Purinas/farmacocinética , Purinas/toxicidade , Pirazóis/farmacocinética , Pirazóis/toxicidade , Pirimidinas/farmacocinética , Pirimidinas/toxicidade , Sulfonamidas/farmacocinética , Sulfonamidas/toxicidadeAssuntos
Colite Ulcerativa , Infecções por Coronavirus , Conduta do Tratamento Medicamentoso , Pandemias , Piperidinas , Pneumonia Viral , Pirimidinas , Pirróis , Adulto , Betacoronavirus/isolamento & purificação , COVID-19 , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/fisiopatologia , Colonoscopia/métodos , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Gravidade do Paciente , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , SARS-CoV-2 , Avaliação de Sintomas , Resultado do TratamentoAssuntos
Bosentana/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Fibrose Pulmonar Idiopática/complicações , Cobertura do Seguro , Fenilpropionatos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/complicações , Pirazóis/uso terapêutico , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Sulfonamidas/uso terapêutico , Cobertura Universal do Seguro de Saúde , Bosentana/efeitos adversos , Humanos , Hipertensão Pulmonar/epidemiologia , Japão , Fenilpropionatos/efeitos adversos , Prevalência , Prognóstico , Pirazóis/efeitos adversos , Piridazinas/efeitos adversos , Pirimidinas/efeitos adversos , Citrato de Sildenafila/efeitos adversos , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
Treatment-free remission (TFR), in which patients discontinue pharmacotherapy and remain in molecular remission, is an emerging treatment goal for patients with chronic myeloid leukemia (CML). Attainment of TFR requires an increased frequency of molecular monitoring, to ensure that patients maintain a deep molecular response. The objective of this analysis was to assess the economic impact of stopping nilotinib among Japanese TFR-eligible patients. A Markov model evaluated the economic impact of TFR among the study population, TFR-eligible CML patients diagnosed since 2012. The model compared patients who had discontinued tyrosine kinase inhibitor (TKI) treatment (ie, attempted TFR) with patients that continued TKI treatment. A 3-y time horizon was modeled from a Japanese public payer perspective. Costs associated with drug treatment, hospital/physician visits, and molecular monitoring were considered. TFR-eligible patients were calculated from Japanese CML incidence rates and efficacy was derived from nilotinib trials. Japanese co-payment maximums were utilized to assess the patient perspective. An estimated 761 and 140 patients were eligible for first- and second-line nilotinib, respectively, in 2019. Assuming that 100% of eligible patients complied, TFR was associated with cost savings of ¥7 625 174 640 (US$66 567 775) over 3 y. In scenarios with reduced willingness to attempt TFR, cost savings persisted. Achievement of TFR was estimated to markedly reduce out-of-pocket expenses for CML patients, regardless of the timing of relapse. Stopping nilotinib for TFR-eligible patients in Japan may result in significant cost savings to both payers and patients. Monitoring costs contributed little to overall annual costs and decreased over time.
Assuntos
Orçamentos , Análise Custo-Benefício , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Custos de Cuidados de Saúde , Humanos , Japão/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cadeias de Markov , Modelos Teóricos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: To summarize patients' preferences for disease-modifying antirheumatic drug (DMARD) therapy in rheumatoid arthritis (RA). METHODS: We conducted a systematic review to identify English-language studies of adult patients with RA that measured patients' preferences for DMARD or health states and treatment outcomes relevant to DMARD decisions. Study quality was assessed using a published quality assessment tool. Data on the importance of treatment attributes and associations with patient characteristics were summarized across studies. RESULTS: From 7951 abstracts, we included 36 studies from a variety of countries. Most studies were in patients with established RA and were rated as medium- (n = 19) or high-quality (n = 12). The methods to elicit preferences varied, with the most common being discrete choice experiment (DCE; n = 13). Despite the heterogeneity of attributes in DCE studies, treatment benefits (disease improvement) were usually more important than both non-serious (6 of 8 studies) and serious adverse events (5 of 8), and route of administration (7 of 9). Among the non-DCE studies, some found that patients placed high importance on treatment benefits, while others (in patients with established RA) found that patients were quite risk averse. Subcutaneous therapy was often but not always preferred over intravenous therapy. Patient preferences were variable and commonly associated with the sociodemographic characteristics. CONCLUSION: Overall, the results showed that many patients place a high value on treatment benefits over other treatment attributes, including serious or minor side effects, cost, or route of administration. The variability in patient preferences highlights the need to individualize treatment choices in RA.
Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Preferência do Paciente/psicologia , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adalimumab/economia , Administração Intravenosa , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Corticosteroides/economia , Adulto , Idoso , Antirreumáticos/economia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/economia , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Piperidinas/economia , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/economia , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Studies assessing ibrutinib's economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT. MATERIALS AND METHODS: Optum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted. RESULTS: TTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib's higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = -$10,615; P < .0001), yielding net savings (MMCD = -$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = -$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy. CONCLUSION: During front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.
Assuntos
Custos de Cuidados de Saúde , Recursos em Saúde , Leucemia Linfocítica Crônica de Células B/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Tempo para o Tratamento , Adenina/análogos & derivados , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Piperidinas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Retratamento , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: There are limited data on treatment patterns, adverse events (AEs), and economic burden in younger, commercially insured patients treated for mantle cell lymphoma (MCL). METHODS: Adults with ≥1 treatment for MCL between 1 November 2013-31 December 2017 were identified from IQVIA Real-World Data Adjudicated Claims-US; index date was first treatment. Patients carried ≥1 MCL diagnosis, were newly treated, and were enrolled continuously for ≥12 months prior to and ≥30 days following index. Patients receiving the four most common MCL regimens were included. Measures included frequency of incident AEs, resource use, and costs overall and by number of AEs. Adjusted logistic regression and generalized linear modeling evaluated risk of hospitalization and all-cause costs per patient per month (PPPM). RESULTS: Two thousand five hundred and nine treated patients had a drug-specific code and were classified to a specific treatment regimen. Of those patients, 1785 patients received at least one of the four most commonly used MCL regimens (R-CHOP, rituximab monotherapy, B-R, and ibrutinib) at some point over follow-up (median 23 months). R-CHOP was the most common regimen observed in the first line (26%), followed by rituximab monotherapy (19%), B-R (15%), and ibrutinib (5%). The median age was 57 years; median Charlson Comorbidity Index was 0. Among patients receiving the four most common regimens, 63% of patients experienced ≥1 incident AE (R-CHOP 77%, B-R 58%, and ibrutinib 52%). An increasing number of incident AEs was associated with increased hospitalization risk (odds ratio = 2.4; 95% Confidence Interval [CI] 2.1-2.7) and increased mean costs PPPM (cost ratio = 1.1; 95% CI 1.1-1.2). DISCUSSION: This is the largest study describing treatment patterns and clinical and economic impact of MCL treatment. The most common regimens were R-CHOP, rituximab monotherapy, B-R, and ibrutinib. The majority of treated patients experienced at least one incident AE, with hospitalization risk and all-cause costs increasing as the number of AEs increased.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Efeitos Psicossociais da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Linfoma de Célula do Manto/tratamento farmacológico , Adenina/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/economia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/economia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Seguimentos , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Seguro Saúde/economia , Seguro Saúde/estatística & dados numéricos , Linfoma de Célula do Manto/economia , Masculino , Pessoa de Meia-Idade , Piperidinas , Padrões de Prática Médica/economia , Padrões de Prática Médica/estatística & dados numéricos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/economia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/economia , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/economia , Estudos Retrospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/economia , Resultado do Tratamento , Estados Unidos/epidemiologia , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/economia , Adulto JovemRESUMO
Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina/efeitos adversos , Deficiência da Di-Hidropirimidina Desidrogenase/diagnóstico , Deficiência da Di-Hidropirimidina Desidrogenase/tratamento farmacológico , Fluoruracila/efeitos adversos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biologia , Pesquisa Biomédica , Neoplasias da Mama/tratamento farmacológico , Capecitabina/uso terapêutico , Neoplasias do Sistema Digestório/tratamento farmacológico , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Feminino , Fluoruracila/uso terapêutico , França , Genótipo , Humanos , Oncologistas , Neoplasias Otorrinolaringológicas/tratamento farmacológico , Farmacovigilância , Guias de Prática Clínica como Assunto , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Mecanismo de ReembolsoRESUMO
Fluoropyrimidines (FLs) have been widely used for more than 60 years against a range of solid tumors and still remains the cornerstone for the treatment of colorectal, gastric, and breast cancer. Here, we performed an economic analysis to estimate the cost of DPYD-guided toxicity management and the clinical benefit expressed as quality adjusted life years (QALYs) in a large group of 571 individuals of Italian origin suffering from cancer and treated with a fluoropyrimidines-based chemotherapy. Individuals suffering from cancer with a histologically confirmed diagnosis of cancer, who received a fluoropyrimidines-based treatment, were retrospectively genotyped in the DPYD gene. Effectiveness was measured as survival of individuals from chemotherapy, while study data on safety and efficacy as well as on resource utilization associated with each adverse drug reaction were used to measure costs to treat these adverse drug reactions. A generalized linear regression model was used to estimate cost differences for both study groups. DPYD extensive metabolizers (528 individuals) had greater effectiveness and lesser cost, representing a cost-saving option over DPYD intermediate and poor metabolizers (43 individuals) with mean QALYs of 4.18 (95%CI: 3.16-5.55) versus 3.02 (95%CI: 1.94-4.25), respectively. Our economic analysis showed that there are some indications for differences in survival between the two groups (p > 0.05), while the cost of DPYD extensive metabolizers was significantly lower (p < 0.01) compared with those belonging to the group of intermediate/poor metabolizers. These findings suggest that DPYD-guided fluoropyrimidines treatment represent a cost-saving choice for individuals suffering from cancer in the Italian healthcare setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Análise Custo-Benefício , Di-Hidrouracila Desidrogenase (NADP)/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia , Testes Genéticos/métodos , Neoplasias/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/genética , Neoplasias/patologia , Prognóstico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Sunitinib and pazopanib are extensively used as first-line treatment of metastatic renal cell carcinoma (mRCC). We performed this meta-analysis to assess the anti-tumor effectiveness, toxicity, and total costs of the two drugs among patients with mRCC/advanced RCC (aRCC). MATERIALS AND METHODS: PubMed, ScienceDirect, Scopus, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Google Scholar were searched to obtain eligible articles. The endpoints included progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and per-patient-per-month (PPPM) costs. RESULTS: We included 14 medium- to high-quality studies. Both drugs were valid for mRCC/aRCC, with equivalent PFS (hazard ratio (HR) =1.06, 95% confidence interval [CI]: 0.98-1.15, P = 0.13), OS (HR = 0.92, 95% CI: 0.79-1.07, P = 0.29), objective response rate (ORR, risk ratio (RR) =1.03, 95% CI: 0.93-1.13, p = 0.58), and disease control rate (DCR, RR = 1.03, 95% CI: 0.94-1.22, P = 0.54). Sunitinib had more dosage reductions and higher PPPM (weighted mean difference = - 1.50 thousand US dollars, 95% CI: - 2.27 to - 0.72, P = 0.0002). Furthermore, more incidences of severe fatigue, thrombocytopenia, and neutropenia were recorded for sunitinib, but pazopanib had more liver toxicity. In subgroup analysis, studies from the US reported longer OS (HR = 0.86, 95% CI: 0.77-0.95, P = 0.004) and higher ORR (RR = 1.24, 95% CI: 1.03-1.51, P = 0.03). CONCLUSIONS: Pazopanib provides equivalent anti-tumor effectiveness and lower PPPM as compared with sunitinib for mRCC/aRCC. Great care should be given to pazopanib-treated patients with abnormal liver function. Nevertheless, more large-scale, high-quality studies are required.
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Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico , Idoso , Antineoplásicos/economia , Fadiga/etiologia , Custos de Cuidados de Saúde , Humanos , Indazóis , Fígado/efeitos dos fármacos , Pessoa de Meia-Idade , Neutropenia/etiologia , Pirimidinas/economia , Estudos Retrospectivos , Sulfonamidas/economia , Sunitinibe/economia , Trombocitopenia/etiologia , Resultado do TratamentoRESUMO
Aims: To evaluate the cost differences between a treatment strategy including tofacitinib (TOFA) vs treatment strategies including adalimumab (ADA), golimumab (GOL), infliximab (IFX), and vedolizumab (VEDO) among all patients with moderate-to-severe ulcerative colitis (UC) (further stratified by patients naïve/exposed to tumor necrosis factor inhibitors [TNFis]). Materials and methods: An Excel-based decision-analytic model was developed to evaluate costs from the perspective of a third-party US payer over 2 years. Efficacy and safety parameters were taken from prescribing information and published trials. All patients started induction therapy on the first treatment in the strategy and continued if efficacy criteria were met and no major adverse event occurred (in which cases they proceeded to the next treatment in the strategy). Results: The cost per member per month (PMPM) of the TOFA->IFX->VEDO->GOL strategy ($1.11) was lower than that of the ADA->IFX->VEDO->GOL strategy ($1.34; Δ = $-0.23) among the TNFi-naïve population (n = 204 patients out of a plan of one million members). Similarly, the use of TOFA before ADA (i.e. TOFA->ADA->IFX-> VEDO) was also associated with lower PMPM costs than the use of ADA before TOFA (i.e. ADA->TOFA->IFX->VEDO): $1.15 vs $1.25 (Δ = $-0.10). Similar, and often larger, differences were observed in both the overall moderate-to-severe population and the TNFi-exposed population. Sensitivity analyses resulted in the same conclusions. Limitations: Our model relied on efficacy data from prescribing information and published trials, which were not head-to-head and slightly differed with respect to methods. Additionally, our model used representative minor and major ADRs (and the associated costs) to represent toxicity management, which was a simplifying assumption. Conclusions: This analysis, the first of its kind to evaluate TOFA vis-à-vis other advanced therapies in the US, suggests the early use of TOFA among both TNFi-naïve and TNFi-failure patients results in lower PMPM costs compared with other treatment alternatives.
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Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/economia , Fármacos Gastrointestinais/uso terapêutico , Gastos em Saúde/estatística & dados numéricos , Piperidinas/economia , Piperidinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Pirróis/economia , Pirróis/uso terapêutico , Adalimumab/economia , Adalimumab/uso terapêutico , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Análise Custo-Benefício , Fármacos Gastrointestinais/efeitos adversos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Infliximab/economia , Infliximab/uso terapêutico , Modelos Econométricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/agonistas , Estados UnidosRESUMO
On December 22, 2017, the U.S. Food and Drug Administration (FDA) updated the product label for nilotinib to include information for providers on how to discontinue this drug in certain patients. With the updated dosing recommendations, select patients with chronic phase myeloid leukemia (CML) taking nilotinib for 3 years or more and whose leukemia has responded with sustained molecular remission (MR4.5, BCR-ABL transcripts of ≤0.0032%) as determined by a FDA-approved test may be eligible to discontinue nilotinib. The updated dosing regimen was based on the efficacy results from two trials that measured how long patients could stop taking nilotinib without the leukemia returning (treatment-free remission). Trial results demonstrated that, among selected patients who received nilotinib as first-line therapy or after transition from imatinib, approximately 50% continued to be in remission at 96 weeks after stopping therapy. Relapses continued to occur throughout the study, indicating that long-term monitoring is needed for safety and disease monitoring. Discontinuation of treatment was associated with an increased risk of low grade musculoskeletal adverse events, some of which were prolonged. Overall, the results support the approval of updates to the dosing recommendations with regard to treatment discontinuation in selected patients who have received nilotinib for at least 3 years, are in a sustained molecular remission, and who can undergo appropriate monitoring. IMPLICATIONS FOR PRACTICE: The updated dosing information provides eligibility criteria for treatment discontinuation, strict monitoring criteria after nilotinib discontinuation, and guidance for treatment reinitiation in eligible patients with chronic phase myeloid leukemia. About half of appropriately selected patients remained in remission 96 weeks after treatment discontinuation. Patients may experience musculoskeletal pain on withdrawal of treatment, incidence of which appears to decrease over time; however, some patients may have long lasting events. The decision to withdraw or continue treatment with nilotinib should be based on clinical condition and patient preferences.
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Antineoplásicos/administração & dosagem , Rotulagem de Medicamentos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pirimidinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Esquema de Medicação , Humanos , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Indução de Remissão/métodos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Adulto JovemRESUMO
OBJECTIVE: Increased incidence of herpes zoster (HZ) has been observed with JAK inhibitors such as tofacitinib. However, whether concomitant methotrexate (MTX) and/or glucocorticoids confer additional (additive or multiplicative) risk is unclear. We evaluated HZ risk in tofacitinib users with and without MTX and glucocorticoids. METHODS: Within MarketScan and Medicare data (2011-2016), we identified all patients with rheumatologist-diagnosed rheumatoid arthritis initiating treatment with tofacitinib (index date); demographics and baseline covariates were evaluated in the year prior to the index date. HZ was ascertained using International Classification of Diseases, Ninth Revision or Tenth Revision codes with antiviral drug use (±7 days). Multivariable Cox regression was used to evaluate hazard ratios (HRs) for HZ in tofacitinib users with and without current concomitant MTX and glucocorticoids, controlling for baseline covariates. RESULTS: We studied 8,030 new tofacitinib users (83.3% women). The mean ± SD age was 60.3 ± 12.6 years. HZ incidence in tofacitinib users was numerically lowest in the absence of glucocorticoids (3.4 per 100 patient-years with MTX; 3.7 per 100 patient-years without MTX). An approximately 2-fold increased incidence of HZ was observed for tofacitinib users receiving either glucocorticoids alone (6.0 per 100 patient-years) or both MTX plus glucocorticoids (6.5 per 100 patient-years). The adjusted HR for HZ in tofacitinib users was unchanged (HR 0.99 [95% confidence interval (95% CI) 0.64-1.54]) when given only with MTX, but was increased (HR 1.96 [95% CI 1.33-2.88]) for tofacitinib plus glucocorticoids. Older age and female sex were also risk factors, while prior vaccination was associated with a strong trend for lower risk. CONCLUSION: In tofacitinib users, HZ occurred at a rate of approximately 4% per year and was further doubled with glucocorticoid exposure. Concomitant MTX did not confer additional risk. Zoster vaccination may decrease risk.