A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

The effectiveness and pharmacoeconomic study of using different corticosteroids in the treatment of hypersensitivity pneumonitis.

PURPOSE: Interstitial lung diseases (ILDs) are caused by inflammation and/or fibrosis of alveolar walls resulting in impaired gas exchange. Hypersensitivity pneumonitis (HP) is the third most common type of ILDs. Corticosteroids are the mainstay treatment for HP. The use of intramuscular (IM) betamethasone or intravenous (IV) dexamethasone as weekly pulse doses has shown higher benefit than daily oral prednisolone for HP patients. The aim of this study is to directly compare different corticosteroids in terms of effectiveness and in monetary values and perform an economic evaluation. METHODS: One hundred and seven patients were tested for pulmonary function tests (PFTs) and inflammatory markers to assess the treatment effectiveness. A cost-effectiveness analysis (CEA) was performed. ICERs between 3 treatment groups were calculated. RESULTS: Post treatment, Krebs von den Lungen-6 (KL-6) levels significantly improved in betamethasone group from 723.22 ± 218.18 U/ml to 554.48 ± 129.69 U/ml (p = 0.001). A significant improvement in erythrocyte sedimentation rate (ESR) occurred in the dexamethasone group from 56.12 ± 27.97 mm to 30.06 ± 16.04 mm (p = 0.048). A significant improvement in forced expiratory volume (FEV1), forced vital capacity (FVC) and six-minute walk distance (6MWD) was observed within the three treatment groups. A significant improvement in oxygen desaturation percentage (SpO2) occurred within dexamethasone and betamethasone groups. Betamethasone and dexamethasone were found more cost-effective than prednisolone as their ICERs fell in quadrant C. Furthermore, ICER between betamethasone and dexamethasone was performed; a small difference in cost was found compared to the higher benefit of betamethasone. CONCLUSION: Betamethasone and dexamethasone were found to be more effective than prednisolone in improving the inflammatory reaction and the clinical features of HP patients. Betamethasone was found to be the best intervention in terms of cost against the effect.

High-dose pulse methylprednisolone vs. dexamethasone standard therapy for severe and critical COVID-19 pneumonia: Efficacy assessment in a retrospective single-centre experience from Malaysia.

INTRODUCTION: The use of dexamethasone (DXM) has been associated with decreased mortality in the patients with hypoxemia during the coronavirus disease-2019 (COVID-19) pandemic, while the outcomes with methylprednisolone (MTP) have been mixed. This real-life study aimed to evaluate the outcomes of patients with severe respiratory failure due to COVID-19 who were treated with high doses of MTP. MATERIALS AND METHODS: This retrospective cohort study enrolled hospitalised patients between May 2021 and August 2021, aged 18 years and above, with severe respiratory failure defined by a ratio of oxygen saturation to fraction of inspired oxygen (SF ratio) of less than 235. The treatment protocol involved administering high-dose MTP for 3 days, followed by DXM, and the outcomes were compared with those of patients who received DXM alone (total treatment duration of 10 days for both groups). RESULTS: A total of 99 patients were enrolled, with 79 (79.8%) receiving pulse MTP therapy and 20 (20.2%) being treated with DXM only. The SF ratio significantly improved from a mean of 144.49 (±45.16) at baseline to 208 (±85.19) at 72 hours (p < 0.05), with a mean difference of 63.51 (p < 0.001) in patients who received ≤750 mg of MTP. Additionally, in patients who received >750 mg of MTP, the SF ratio improved from a baseline mean of 130.39 (±34.53) to 208.44 (±86.61) at 72 hours (p < 0.05), with a mean difference of 78.05 (p = 0.001). In contrast, patients who received DXM only demonstrated an SF ratio of 132.85 (±44.1) at baseline, which changed minimally to 133.35 (±44.4) at 72 hours (p = 0.33), with a mean difference of 0.50 (p = 0.972). The incidence of nosocomial infection was higher in the MTP group compared with the DXM group (40.5% vs. 35%, p = 0.653), with a relative risk of 1.16 (95% CI: 0.60-2.23). CONCLUSION: MTP did not demonstrate a significant reduction in intubation or intensive care unit admissions. Although a high dose of MTP improved gas exchange in patients with severe and critical COVID-19, it did not provide an overall mortality benefit compared to standard treatment.

Olanzapine cost-effectiveness in vomiting and nausea from highly emetogenic chemotherapy in children and adolescents.

OBJECTIVES: To assess the cost-effectiveness of addition of olanzapine to a prophylactic antiemetic regimen containing aprepitant, dexamethasone and ondansetron among children receiving highly emetogenic chemotherapy (HEC) in India, Bangladesh, Indonesia, the UK and the USA. METHODS: Health states were estimated using individual patient-level outcome data from a randomised trial. The incremental cost-utility ratio (ICUR), incremental cost-effectiveness ratio and net monetary benefit (NMB) were calculated from the patient perspective for India, Bangladesh, Indonesia, the UK and the USA. One-way sensitivity analysis was done by varying the cost of olanzapine, cost of hospitalisation and utility values by ±25%. RESULTS: The olanzapine arm had an increment of 0.0018 quality-adjusted life-years (QALY) over the control arm. The mean total expenditure in the olanzapine arm was greater by US$0.51, US$0.43, US$6.73, US$11.05 and US$12.35 in India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR($/QALY) was US$282.60 in India, US$241.42 in Bangladesh, US$3755.93 in Indonesia, US$6161.83 in the UK and US$6887.41 in the USA. The NMB was US$9.86, US$10.12, US$14.08, US$44.74 and US$98.79 for India, Bangladesh, Indonesia, the UK and the USA, respectively. The ICUR estimates of the base case and sensitivity analysis were below the willingness-to-pay threshold in all scenarios. CONCLUSION: The addition of olanzapine as a fourth agent for antiemetic prophylaxis is cost-effective despite an increase in overall expenditure. Olanzapine should be uniformly considered for children receiving HEC.

A Phase II Study to Evaluate the Efficacy of Bortezomib in Combination with Thalidomide in Treatment-Naïve Waldenstrom Macroglobulinemia Patients.

PURPOSE: Despite the recent success of Bruton's tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM. MATERIALS AND METHODS: Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM. RESULTS: A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade ≥ 3 AE was anemia (21.4%). CONCLUSION: All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity.

Daratumumabe em combinação com bortezomibe e dexametasona para o tratamento de pacientes com mieloma múltiplo recidivado e/ou refratário que receberam uma única terapia prévia no Sistema Único de Saúde (SUS) / Daratumumab in combination with bortezomib and dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma who have received a single prior therapy in the Unified Health System (SUS)

INTRODUÇÃO: O mieloma múltiplo (MM) é uma neoplasia maligna, caracterizada pela proliferação desregulada de plasmócitos (responsáveis pela produção de anticorpos), resultando principalmente em produção exacerbada de imunoglobulina não funcional. As manifestações clínicas mais comuns são dores ósseas e fraturas, anemia, insuficiência renal e infecções recorrentes. É a segunda neoplasia hematológica mais frequente (10-15% dos casos) e representa 1% de todos os tumores malignos, sendo considerada uma doença progressiva e sem cura, com a maioria dos pacientes apresentando múltiplas remissões e recidivas. O manejo terapêutico de MM recidivado e /ou refratário (MMRR) ainda é um desafio devido ao aumento da resistência às terapias, piora do prognóstico e declínio da qualidade de vida desses pacientes conforme progridem nas linhas de tratamento. HISTÓRICO DE RECOMENDAÇÕES DA CONITEC: Em fevereiro de 2022 foi publicado o Relatório de Recomendação nº 702 analisando o uso de daratumumabe para o controle do MMRR. A recomendação da Conitec e decisão do Ministério da Saúde foi pela não incorporação no SUS, considerando os indicadores de eficiência apresentados e a estimativa elevada de impacto orçamentário. Diferente da demanda de 2022, a solicitação atual, propõe o uso de daratumumabe em associação com bortezomibe e dexametasona apenas para pacientes com MMRR que receberam uma única terapia prévia. PE

Implante biodegradável de dexametasona para o tratamento do edema macular diabético em maiores de 18 anos, conforme Protocolo Clínico do Ministério da Saúde / Biodegradable dexamethasone implant for the treatment of diabetic macular edema in people over 18 years of age, according to the Clinical Protocol of the Ministry of Health

INTRODUÇÃO: A retinopatia diabética, a principal causa de cegueira em pessoas em idade laboral, é uma manifestação do diabetes na forma de lesão de órgãos-alvo. Clinicamente, as primeiras lesões são anormalidades vasculares como microaneurismas, hemorragias e exsudatos. O aumento da vasopermeabilidade resulta em espessamento da retina e/ou depósitos lipídicos. Quando esses eventos ocorrem na mácula, instala-se o edema macular diabético (EMD), levando ao risco de perda visual central. Dois mecanismos fundamentais estão envolvidos no EMD: angiogênese e inflamação. A angiogênese é secundária ao aumento da expressão de VEGF, principal molécula envolvida na perda da ruptura da barreira hemato-retiniana, que por sua vez causa a exsudação e espessamento macular. A inflamação pode ser causa ou consequência da angiogênese, atualmente considerada fator interdependente. Citocinas encontram-se elevadas em pacientes com retinopatia diabética e EMD, tendo correlação positiva com a severidade da doença ocular. O PCDT atual de retinopatia diabética, publicado pelo Ministério da Saúde, inclui os antiVEGFs ranibizumabe e aflibercepte para pacientes sem tratamento medicamentoso prévio, associado ou não à fotocoagulação a laser, para o EMD, mas não contempla a corticoterapia para o bloqueio da produção dos mediadores inflamatórios e barreira vascular endotelial. Por este motivo ainda existem necessidades não atendidas no cenário de tratamento das retinopatias diabéticas, especialmente relacionadas ao EMD. De acordo com a literatura, pacientes vitrectomizados, pacientes com eventos tromboembólicos recentes ou que não apresentaram resposta satisfatória ao tratamento com os antiangiogênicos, por exemplo, se encontram desassistidos pelo PCDT, além das dificuldades relacionadas ao regime de aplicações dos anti-VEGFs (injeções frequentes com deslocamentos aos serviços em saúde), complicando o atendimento no SUS. Ainda, relacionado às complicações da retinopatia diabética e qualidade de vida dos pacientes, a falta de tratamento ou tratamento subotimo pode levar à cegueira, além de outras complicações. BREVE HISTÓRICO: Em 2020 a tecnologia foi submetida e teve recomendação desfavorável devido as incertezas frente à ineficácia terapêutica, ausência de evidências robustas e falta de informação sobre delimitação e escopo para uso no SUS. PERGUNTA: O uso do implante intravítreo de dexametasona é seguro e efetivo no tratamento tratamento de adultos com edema macular diabético , como opção terapêutica no SUS? EVIDÊNCIAS CLÍNICAS: As evidências de eficácia e segurança do implante intravítreo de dexametasona são baseadas no estudo pivotal do implante intravítreo de dexametasona e em três estudos de comparação direta com os antiVEGFs, já incorporados ao SUS. O estudo pivotal que comparou o implante de dexametasona ao placebo, utilizando adicionalmente ou não a fotocoagulação a laser, demonstrou melhora da acuidade visual maior ou igual a 15 letras da linha de base do estudo, em ambos os braços de tratamento (DEXi 0,7 e 0,35 mg) em relação ao grupo placebo tratado apenas com fotocoagulação a laser. A melhora significativa no BCVA (do inglês, Best Corrected Visual Acuity) ocorreu independentemente do status do cristalino na linha de base do estudo. Os resultados do primeiro estudo de comparação direta são de não-inferioridade da dexametasona em relação ao ranibizumabe e redução do número de injeções realizadas, com perfil de segurança aceitável. O segundo estudo demonstrou equivalência da dexametasona ao tratamento com aflibercepte, uma vez que a diferença em BCVA não foi clinicamente significativa. O terceiro ECR de comparação direta incluído aponta para a segurança e eficácia em melhorar a BCVA e diminuir a espessura da mácula central, em pacientes com EMD, por ambos os implantes intravítreos (dexametasona vs ranibizumabe). A avaliação da qualidade metodológica dos ECRs foi realizada e os riscos de vieses foram descritos sendo de baixo risco, em sua maioria. AVALIAÇÃO ECONÔMICA: O presente dossiê demonstrou que Ozurdex se configura como uma tecnologia poupadora de recursos para o sistema de saúde, através de apresentação de uma análise de custo-minimização abrangente, que incluiu custos de medicação, custos de administração e custos relativos a potenciais eventos adversos. Através de uma análise de cenários que variou os principais parâmetros tais como horizonte temporal (1 ou 3 anos), e custo de aquisição dos comparadores (anti-VEGFs), valor de APAC (forma de financiamento dos antiangiogênicos) ou custo do frasco-ampola proposto pelos fabricantes em suas solicitações de incorporação, foi possível demonstrar que o tratamento com Ozurdex pode proporcionar economia de recursos que varia de R$ 1.533,21 até R$ 15.651,77 por paciente, em comparação aos anti-VEGFs. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Na análise de impacto orçamentário, foram avaliados sete cenários com combinações de diferentes valores para os comparadores (APAC e custo frasco-ampola), estimativas populacionais (epidemiológica ou demanda aferida) e dois possíveis comportamentos de market shares. A economia projetada foi de pelo menos R$ 8 milhões, avaliando o cenário mais conservador. Nos demais cenários as economias projetadas foram de R$ 16 e R$ 39 milhões, e entre R$ 148 e R$ 716 milhões em estimativa de usuários consideravelmente maior. Os montantes apresentados podem contribuir para a otimização dos recursos no manejo dos pacientes com RD. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas 3 tecnologias para compor o esquema terapêutico do edema macular diabético em adultos. São 3 anticorpos monoclonais inibidores do crescimento do endotélio vascular (VEGF): brolucizumabe, faricimabe e tarcocimabe tedromer, sendo que o segundo apresenta também ação anti-angiopoietina 2 (Ang-2). O brolucizumabe e faricimabe estão registrados na FDA e EMA desde 2022. O tarcocimabe está em fase 3 e pode apresentar resultados dos ensaios a partir de 2023. CONSIDERAÇÕES FINAIS: Adicionalmente às evidências clínicas de qualidade, a avaliação de custo-minimização possui e a análise de impacto orçamentário possuem incertezas em relação à definição de custos e cenários de comparação, mas que sugerem dominância do Implante biodegradável de dexametasona para tratamento do edema macular diabético sob a perspectiva do Sistema Único de Saúde. PERSPECTIVA DO PACIENTE: Foi aberta a Chamada Pública nº 09/2022 de 13 a 26 de fevereiro 2022 e duas pessoas se inscreveram, ambas representantes de associações de pacientes. A definição dos representantes titular e suplente foi determinada por decisão consensual entre o grupo de inscritos. A representante leu três relatos de pacientes que possuem edema macular diabético e recorrem ao DEXi. Os três pacientes iniciaram o tratamento com um antiangiogênico e, após o uso do DEXi, apresentaram melhora dos sintomas e o alcance de maior qualidade de vida. Nenhum deles manifestou eventos adversos após o uso do implante. RECOMENDAÇÃO PRELIMINAR: Os membros do plenário, presentes na 118ª Reunião ordinária da Conitec, no dia 03 de maio de 2023, deliberaram por unanimidade encaminhar para a consulta pública com recomendação favorável a incorporação do implante biodegradável de dexametasona para o tratamento do edema macular diabético (EMD) em maiores de 18 anos no SUS. CONSULTA PÚBLICA: Realizada no período de 03 de julho a 24 de julho do presente ano, teve 62 contribuições de caráter técnico-científico e 146 respostas tidas como de experiência ou opinião. As contribuições recebidas na consulta pública sobre o relatório que avalia a proposta de incorporação do Implante biodegradável de dexametasona para o tratamento do edema macular diabético (EMD) em maiores de 18 anos no SUS foram majoritariamente favoráveis a recomendação preliminar da Conitec, de incorporação. Não foram adicionadas na consulta pública, referências que alterassem a análise da evidência apresentada no relatório, apenas atualização pelo demandante. RECOMENDAÇÃO FINAL: Os membros do plenário, presentes na 121ª Reunião ordinária da Conitec, no dia 02 de agosto de 2023, deliberaram por unanimidade recomendar a incorporação do implante biodegradável de dexametasona para o tratamento do edema macular diabético (EMD) em maiores de 18 anos conforme Protocolo Clínico do Ministério da Saúde, sob registro de deliberação 840/2023. Para tal recomendação, levou-se em consideração, entre outros fatores, que há economia de recursos em todos os cenários analisados e que os estudos demostraram que o benefício clínico do implante de dexametasona é maximizado para algumas populações, que atualmente encontram-se desassistidas ou subtratadas devido à ausência de uma opção de corticoterapia no âmbito do SUS. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, o implante biodegradável de dexametasona para o tratamento do edema macular diabético em maiores de 18 anos, conforme Protocolo Clínico do Ministério da Saúde, publicada no Diário Oficial da União nº 193, seção 1, página 143, em 9 de outubro de 2023.

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies.

INTRODUCTION: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN. METHODS: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022). RESULTS: In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports. CONCLUSION: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).

Antiemetic Administration and Its Association with Race: A Retrospective Cohort Study.

BACKGROUND: Anesthesiologists' contribution to perioperative healthcare disparities remains unclear because patient and surgeon preferences can influence care choices. Postoperative nausea and vomiting is a patient- centered outcome measure and a main driver of unplanned admissions. Antiemetic administration is under the sole domain of anesthesiologists. In a U.S. sample, Medicaid insured versus commercially insured patients and those with lower versus higher median income had reduced antiemetic administration, but not all risk factors were controlled for. This study examined whether a patient's race is associated with perioperative antiemetic administration and hypothesized that Black versus White race is associated with reduced receipt of antiemetics. METHODS: An analysis was performed of 2004 to 2018 Multicenter Perioperative Outcomes Group data. The primary outcome of interest was administration of either ondansetron or dexamethasone; secondary outcomes were administration of each drug individually or both drugs together. The confounder-adjusted analysis included relevant patient demographics (Apfel postoperative nausea and vomiting risk factors: sex, smoking history, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use; as well as age) and included institutions as random effects. RESULTS: The Multicenter Perioperative Outcomes Group data contained 5.1 million anesthetic cases from 39 institutions located in the United States and The Netherlands. Multivariable regression demonstrates that Black patients were less likely to receive antiemetic administration with either ondansetron or dexamethasone than White patients (290,208 of 496,456 [58.5%] vs. 2.24 million of 3.49 million [64.1%]; adjusted odds ratio, 0.82; 95% CI, 0.81 to 0.82; P < 0.001). Black as compared to White patients were less likely to receive any dexamethasone (140,642 of 496,456 [28.3%] vs. 1.29 million of 3.49 million [37.0%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.78; P < 0.001), any ondansetron (262,086 of 496,456 [52.8%] vs. 1.96 million of 3.49 million [56.1%]; adjusted odds ratio, 0.84; 95% CI, 0.84 to 0.85; P < 0.001), and dexamethasone and ondansetron together (112,520 of 496,456 [22.7%] vs. 1.0 million of 3.49 million [28.9%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.79; P < 0.001). CONCLUSIONS: In a perioperative registry data set, Black versus White patient race was associated with less antiemetic administration, after controlling for all accepted postoperative nausea and vomiting risk factors.

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

Importance: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. Objective: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants. Design, Setting, and Participants: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Exposure: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. Main Outcomes and Measures: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age. Results: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Conclusions and Relevance: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

Cost-Effectiveness of Dexamethasone Intravitreal Implant in Naïve and Previously Treated Patients with Diabetic Macular Edema.

PURPOSE: To compare the direct costs associated with the dexamethasone intravitreal implant (DEX-i) in treatment-naïve and previously treated eyes with diabetic macular edema (DME) in a real clinical setting. METHODS: Retrospective and single-center study conducted in a real clinical scenario. Consecutive DME patients, either naïve or previously treated with vascular endothelial growth factor inhibitors (anti-VEGF), who received treatment with one or more DEX-i between May 2015 and December 2020, and who were followed-up for a minimum of 12 months, were included in the study. The cost analysis was performed from the perspective of the Andalusian Regional Healthcare Service. The primary effectiveness endpoint was the probability of achieving an improvement in best-corrected visual acuity (BCVA) ≥ 15 ETDRS letters after 1 year of treatment. The incremental cost-effectiveness ratio (ICER) of different improvements in BCVA was calculated. RESULTS: Forty-nine eyes, twenty-eight (57.1%) eyes from the treatment-naïve group and twenty-one (42.9%) from the previously treated group, were included in the analysis. The total cost of one year of treatment was significantly lower in the treatment-naïve eyes than in the previously treated eyes [Hodges-Lehmann median difference: EUR 819.1; 95% confidence interval (CI): EUR 786.9 to EUR 1572.8; p < 0.0001]. The probability of achieving a BCVA improvement of ≥15 letters at month 12 was significantly greater in the treatment-naïve group than in the previously treated group (rate difference: 0.321; 95% CI: 0.066 to 0.709; p = 0.0272). The Cochran-Mantel-Haenszel Odds Ratio of achieving a BCVA improvement of ≥15 letters at month 12 was 3.55 (95% CI: 1.09 to 11.58; p = 0.0309). In terms of ICER, the treatment-naïve group showed cost savings of EUR 7704.2 and EUR 5994.2 for achieving an improvement in BCVA ≥ 15 letters at month 12 and at any of the measured time points, respectively. CONCLUSIONS: DEX-i was found to be more cost-effective in treatment-naïve eyes than in those previously treated with anti-VEGF. Further studies are needed to determine the most cost-effective treatment based on patient profile.

Assessment of postoperative pain in patients undergoing temporomandibular joint arthroscopy with infiltration of dexamethasone disodium phosphate in different concentrations. A randomized controlled trial.

The main aim of this work was to evaluate the effect of intra-articular, sub-synovial steroid injections (IASSSI) with different doses during temporomandibular joint (TMJ) arthroscopy. Using a single-blind, randomized clinical trial, the investigators enrolled a sample of subjects who underwent TMJ arthroscopy with vs. without IASSSI for treating TMJ disorder (TMD). The predictor variable was the treatment group classified as no treatment (A - without IASSSI) or active treatments (IASSSI (B) with 2 mg or (C) 4-mg dexamethasone). Study medications were randomly assigned. Only subjects were blinded to treatment assignment. The main outcome variables included the following: 1) pain assessed up to postoperative day 30 with the McGill Pain Questionnaire and visual analog scale (VAS); 2) maximum mouth opening (MMO); and 3) analgesic and anti-inflammatory drug consumption. Other variables were demographic (age, sex) or pathologic (disease manifestations and classifications). Descriptive and bivariate statistics were computed. Statistical significance was set at p ≤ 0.5, one-tailed test of hypothesis. The sample comprised 36 patients (n = 12 per study group). In the active group with 4 mg corticosteroids, pain reduction measured by VAS (odds ratio [OR] = 0.18; p = 0.013) and McGill scale scores (OR = 0.15; p = 0.048) was significantly higher than in the control group. The McGill scale scores significantly decreased in both IASSSI groups, compared to the control group, at the final follow-up (all p < 0.012), and IASSSI was significantly associated with reduced analgesic consumption at postoperative days 7 and 14 (p = 0.003). However, there was no significant difference regarding MMO among the three groups. Within the limitations of the study, it seems that intra-articular, sub-synovial steroid injections (IASSSI) with 4 mg dexamethasone should be preferred whenever appropriate when pain relief is the priority of the procedure. Brazilian Registry of Clinical Trials (ReBec)- 28yb2g.

Artificial intelligence assessment of the potential of tocilizumab along with corticosteroids therapy for the management of COVID-19 evoked acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS), associated with high mortality rate, affects up to 67% of hospitalized COVID-19 patients. Early evidence indicated that the pathogenesis of COVID-19 evoked ARDS is, at least partially, mediated by hyperinflammatory cytokine storm in which interleukin 6 (IL-6) plays an essential role. The corticosteroid dexamethasone is an effective treatment for severe COVID-19 related ARDS. However, trials of other immunomodulatory therapies, including anti-IL6 agents such as tocilizumab and sarilumab, have shown limited evidence of benefit as monotherapy. But recently published large trials have reported added benefit of tocilizumab in combination with dexamethasone in severe COVID-19 related ARDS. In silico tools can be useful to shed light on the mechanisms evoked by SARS-CoV-2 infection and of the potential therapeutic approaches. Therapeutic performance mapping system (TPMS), based on systems biology and artificial intelligence, integrate available biological, pharmacological and medical knowledge to create mathematical models of the disease. This technology was used to identify the pharmacological mechanism of dexamethasone, with or without tocilizumab, in the management of COVID-19 evoked ARDS. The results showed that while dexamethasone would be addressing a wider range of pathological processes with low intensity, tocilizumab might provide a more direct and intense effect upon the cytokine storm. Based on this in silico study, we conclude that the use of tocilizumab alongside dexamethasone is predicted to induce a synergistic effect in dampening inflammation and subsequent pathological processes, supporting the beneficial effect of the combined therapy in critically ill patients. Future research will allow identifying the ideal subpopulation of patients that would benefit better from this combined treatment.

Reducing oral steroid intolerability and drug costs for acute wheezers: A retrospective evaluation of a clinical management algorithm in a Pediatric Emergency Department.

PROJECT AIM: To retrospectively evaluate a clinical management algorithm for acute wheezers in a UK Pediatric Emergency Department (PED). OVERVIEW AND RATIONALE: Acute wheezing attacks are a leading cause of PED attendances and inpatient admissions. Prednisolone, a routine treatment, is intolerable in almost one-third of children, requiring repeated dosing, which may prolong length of stay (LOS). To address this problem, we: (1) developed an acute management algorithm (concise, single-sided flow-chart, instructing immediate management); (2) modified the OCS regime from prednisolone (1 mg/kg, 3-day course) to dexamethasone (600 then 300 mcg/kg); (3) and disseminated guidance regionally. Written information-handouts, e-mails, and posters-were followed-up with verbal reinforcement. We implemented the algorithm in 2017 and revised it further in 2018. EVALUATION: In 2019, we retrospectively collected data on 100 acute wheeze attendances (those requiring OCS, aged 2-14), between October and December in 2016, 2017, and 2018 (n = 300), and assessed outcomes. RESULTS: Over a 48-month period, we reduced OCS intolerability by 67.2% and OCS drug costs by 85.8% (saving £41,470.14), while not significantly influencing the other outcomes. CONCLUSIONS: Reduced intolerability and substantial cost savings can be achieved by implementing a structured acute pediatric wheeze algorithm and modifying the OCS to single-dose dexamethasone (300 mcg/kg).

Racial Disparities in Pulse Oximeter Device Inaccuracy and Estimated Clinical Impact on COVID-19 Treatment Course.

Arterial blood oxygen saturation as measured by pulse oximetry (peripheral oxygen saturation (SpO2)) may be differentially less accurate for people with darker skin pigmentation, which could potentially affect the course of coronavirus disease 2019 (COVID-19) treatment. We analyzed pulse oximeter accuracy and its association with COVID-19 treatment outcomes using electronic health record data from Sutter Health, a large, mixed-payer, integrated health-care delivery system in Northern California. We analyzed 2 cohorts: 1) 43,753 non-Hispanic White (NHW) or non-Hispanic Black/African-American (NHB) adults with concurrent arterial blood gas oxygen saturation/SpO2 measurements taken between January 2020 and February 2021; and 2) 8,735 adults who went to a hospital emergency department with COVID-19 between July 2020 and February 2021. Pulse oximetry systematically overestimated blood oxygenation by 1% more in NHB individuals than in NHW individuals. For people with COVID-19, this was associated with lower admission probability (-3.1 percentage points), dexamethasone treatment (-3.1 percentage points), and supplemental oxygen treatment (-4.5 percentage points), as well as increased time to treatment: 37.2 minutes before dexamethasone initiation and 278.5 minutes before initiation of supplemental oxygen. These results call for additional investigation of pulse oximeters and suggest that current guidelines for development, testing, and calibration of these devices should be revisited, investigated, and revised.

Eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab / Efficacy and safety of intravitreal sustained-release dexamethasone implant for the treatment of adult patients with macular edema secondary to retinal vein occlusion with decreased visual acuity and/or increased or maintained macular thickness despite the use of three injections of bevacizumab

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N' 111-IETSI-ESSALUD-2021 se ha elaborado el presente dictamen. el cual expone la evaluación de la eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. Así. la médica Fiorella Norabuena Mautino. especialista en oftalmología del Servicio de Retina, a través del Comité Farmacoterapéutico del Hospital Nacional Edgardo Rebagliati Martins y siguiendo la Directiva N' 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de autorización de uso del producto farmacéutico dexametasona (implante intravítreo) no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES: La oclusión venosa retiniana (OVR), una obstrucción parcial o completa del sistema venoso retinal, es considerada la segunda causa más común de trastorno vascular de la retina (Cugati et al., 2006; PAAO, 2019), y es una causa importante de pérdida de la visión en adultos a nivel mundial (Rogers et al., 2010: Song et al., 2019). En el 2015, se estimó que la prevalencia global de la OVR en personas de entre 30 y 89 años fue de 0.77 % (Song et al., 2019). Los dos tipos más comunes de OVR, son la oclusión de la rama venosa de la retina (ORVR), que ocurre en la vena retinal distal y ocasiona hemorragia en un vaso pequeño de la retina; y la oclusión de la vena central de la retina (OVCR), que ocurre en la vena retinal proximal y ocasiona hemorragia en toda la retina (Han & Ahmad, 2021). En un estudio realizado con datos de Europa, Asia, Australia y Estados Unidos se reporta que la prevalencia ajustada por edad y sexo de la ORVR es de 3.77 por 1000 personas, y de la OVCR es de 0.65 por 1000 personas. METODOLOGÍA: Se realizó una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad del uso de IIDLPS en el tratamiento de pacientes adultos con EM secundario a ORVR u OVCR con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library, LILACS y The Web of Science. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas. evaluaciones de tecnologías sanitarias y guías de práctica clínica. tales como The National Institute for Health and Care Excellence (NICE). RESULTADOS: De la búsqueda bibliográfica, se incluyó una GPC elaborada por The Royal College of Ophthalmologists (RCO) (The Royal College of Ophthalmologists. 2022). y tres estudios retrospectivos que evaluaron el cambio de bevacizumab a IIDLPS (Chiquet et al.. 2016: Lee et al.. 2017: Sharareh et al., 2013). Además se incluyeron dos GPC que fueron sugeridas por los especialistas de EsSalud, elaboradas por The European Society of Retina Specialists (EURETINA) (Schmidt-Erfurth et al., 2019) y la Sociedad Española de Retina y Vítreo (SERV) (SERV, 2015). No se identificaron RS con MA ni ETS que respondan a la pregunta PICO del presente dictamen. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de implante intravitreo de dexametasona de liberación prolongada sostenida (IIDLPS) para el tratamiento de pacientes adultos con edema macular (EM) secundario a oclusión de la vena central de la retina (OVCR) u oclusión de la rama venosa de la retina (ORVR) con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud. según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de 1 año a partir de la fecha de publicación. La continuación de dicha aprobación está sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Antenatal dexamethasone for improving preterm newborn outcomes in low-resource countries: a cost-effectiveness analysis of the WHO ACTION-I trial.

BACKGROUND: After considerable debate, there is now unequivocal evidence that use of antenatal corticosteroids improves outcomes in preterm neonates when used in women at risk of early preterm birth in reasonably equipped hospitals in low-resource countries. We aimed to evaluate the cost-effectiveness of dexamethasone administration in the management of preterm birth in a cohort of pregnant women from five low-resource countries. METHODS: We performed a cost-effectiveness analysis using data from 2828 women (and 3051 babies) who participated in the WHO ACTION-I trial, a multicentre, randomised, placebo-controlled trial that assessed the safety and efficacy of dexamethasone in pregnant women at risk of early preterm birth in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. We used a decision tree model to assess the cost-effectiveness of dexamethasone treatment compared with no intervention from a health-care sector perspective. Outcome data were taken from the primary results of the trial and primary data on cost were collected in 28 hospitals. The primary cost-effectiveness outcome was cost per neonatal death or the cost per disability-adjusted life-years (DALYs) averted, or costs saved per 1000 woman-baby units if the intervention was found to be cost-saving. FINDINGS: Administration of dexamethasone averted 38 neonatal deaths per 1000 woman-baby units and 1132 DALYs per 1000 woman-baby units. Compared with no intervention, use of antenatal corticosteroids was cost-saving in all five countries, ranging from a saving of US$1778 per 1000 woman-baby units (95% uncertainty interval [UI] -13 878 to 9483) in Nigeria, to $20 531 per 1000 woman-baby units (-46 387 to 4897) in Pakistan, to $36 870 per 1000 woman-baby units (-61 569 to -15 672) in Bangladesh, to $38 303 per 1000 woman-baby units (-64 183 to -10 753) in India, and to $53 681 per 1000 woman-baby units (-113 822 to 2394) in Kenya. Findings remained consistent following sensitivity analyses. In all five countries, dexamethasone was more effective and cost less compared with no treatment. INTERPRETATION: Antenatal dexamethasone for early preterm birth was cost-saving when used in hospitals in low-resource countries. Decision makers in low-resource settings can be confident that use of antenatal dexamethasone for early preterm birth is cost-effective, and often cost-saving when used in reasonably equipped hospitals in low-resource countries. FUNDING: Bill & Melinda Gates Foundation and WHO.

Carfilzomibe no tratamento de pacientes com mieloma múltiplo recidivado ou refratário, que receberam terapia prévia / Carfilzomib in the treatment of patients with relapsed or refractory multiple myeloma who have received prior therapy

INTRODUÇÃO: O mieloma múltiplo (MM) é uma neoplasia hematológica maligna caracterizada pela proliferação descontrolada de plasmócitos alterados na medula óssea, resultando na produção aumentada de imunoglobulinas não funcional (proteína monoclonal). O acúmulo destas imunoglobulinas e a interação dos plasmócitos com outras células da medula óssea resultam em anemia, lesões ósseas, infecções, hipercalcemia, injúria renal, fadiga e dor. A incidência mundial informada pelo Globocan é de 2,2 novos casos por 100.000 habitantes em homens e 1,5/100.000 em mulheres, com ocorrência, a nível mundial, de 176 mil novos casos e 117 mil mortes em 2020. Carfilzomibe é um agente antineoplásico, inibidor de proteassoma que se liga seletiva e irreversivelmente nos sítios ativos. Tem atividade antiproliferativa e pró-apoptóticas. PERGUNTA DE PESQUISA: Kyprolis® (carfilzomibe) em combinação com dexametasona é eficaz e seguro no tratamento de pacientes com mieloma múltiplo recidivado ou refratário que receberam uma terapia prévia quando em comparação a bortezomibe, ciclofosfamida, dexametasona, cisplatina, doxorrubicina, doxorrubicina lipossomal, etoposídeo, melfalana, vincristina ou talidomida? EVIDÊNCIAS CLÍNICAS: O demandante realizou as buscas na literatura utilizando as seguintes bases de dados: The Cochrane Library, Medline via PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Centre for Reviews and Dissemination (CRD), o que resultou na inclusão de 14 publicações. Na análise conduzida pela Secretaria Executiva foram consideradas 12 publicações referentes a um ensaio clínico randomizado e uma publicação de revisão sistemática. O estudo ENDEAVOR foi um ensaio clínico de fase III, multicêntrico, aberto, que incluiu 929 participantes randomizados para receber carfilzomibe+dexametasona ou bortezomibe+dexametasona. A mediana de SLP foi 18,7 meses (IC 95%, 15,6 a não estimável) no grupo que recebeu carfilzomibe comparado a 9,4 meses (IC 95%, 8,4 a 10,4) no grupo que recebeu bortezomibe, resultando em uma magnitude de benefício absoluto de 9,3 meses (HR 0,53 [IC95% 0,44 a 0,65]; p< 0,0001). A duração mediana de resposta foi 21,3 meses (IC95% 21,3 a não estimável) no grupo carfilzomibe e 10,4 meses (IC95% 9,3 a 13,8) no grupo bortezomibe. Em ambos os grupos, 98% dos participantes apresentaram eventos adversos (qualquer grau), sendo a anemia (43% versus 28%), diarreia (36,7% versus 40,6%) e febre (32,6% versus 15,4%) os eventos mais frequentes nos grupos carfilzomibe e bortezomibe, respectivamente. Os eventos adversos mais comuns grau 3 ou maior foram reportados em 81,9% dos participantes do grupo carfilzomibe (n=379) e 71,1% no grupo bortezomibe (n=324), sendo a anemia (17,3% no grupo carfilzomibe e 10,1% no grupo bortezomibe), hipertensão (14,9% versus 3,3%), trombocitopenia (12,5% versus 14,7%),os três eventos mais frequentes. Insuficiência cardíaca grau 3 ou superior, foi mais frequente no grupo carfilzomibe (6%) que no grupo bortezomibe (2%.). AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-efetividade. Na análise do cenário base, em um horizonte temporal de 30 anos, carfilzomibe acrescentou ganhos incrementais de 1,19 QALY, resultando em uma razão de custo utilidade incremental (RCEI) de R$ 195.310,00 por QALY. No cenário proposto pela Secretária-Executiva (horizonte temporal de 10 anos e valor de utilidade derivada do estudo ENDEAVOR), carfilzomibe gerou benefício de 0,63 QALY, com RCEI de R$ 365.830,00 por QALY. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Com o desconto apresentado pelo demandante, a incorporação de carfilzomibe ao SUS implica em custos adicionais ao sistema de saúde no montante de aproximadamente R$ 365 milhões em cinco anos. A principal limitação da análise foi a estimativa da população. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram identificadas 10 tecnologias potenciais para compor o esquema terapêutico de pacientes adultos com mieloma múltiplo recidivado ou refratário: Belantamabe mafodotin, Ciltacabtageno autoleucel, Elranatamab, Iberdomida, Idecabtagene vicleucel, Isatuximabe, nivolumabe, selinexor, teclistamab, venetoclax. Tais medicamentos são anticorpo monoclonal ligado a um antineoplásico, anticorpo biespecífico, anticorpo monoclonal, imumodulador, terapias baseadas em células T autólogas geneticamente modificadas (CAR-T), inibidor SINE, ou inibidor de Bcl-2. A maioria não possui registro na FDA, EMA ou Anvisa. CONSIDERAÇÕES FINAIS: Os resultados sugerem eficácia e segurança do carfilzomibe na população elegível, porém, no horizonte temporal de 10 anos, com QALY < 1, RCEI de R$ 365.830,00 por QALY e impacto orçamentário de aproximadamente R$ 17 milhões no primeiro ano de incorporação e R$ 131 milhões no 5º ano da incorporação, totalizando R$ 365 milhões em cinco anos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Plenário presentes na 109ª Reunião Ordinária da Conitec, realizada no dia 08 de junho de 2022, sem nenhuma declaração de conflito de interesse, deliberaram por unanimidade, encaminhar o tema para consulta pública com recomendação preliminar desfavorável à incorporação de carfilzomibe para o tratamento de mieloma múltiplo recidivado ou refratário no SUS. Os membros consideraram a evidência científica boa e favorável ao carfilzomibe, porém, a RCEI e o impacto orçamentário foram considerados muito altos para o tratamento de uma doença que já tem outras opções terapêuticas disponíveis no SUS. CONSULTA PÚBLICA: Entre os dias 08/07/2022 e 27/07/2022 foram recebidas 421 contribuições, sendo 152 pelo formulário para contribuições técnico-científicas e 269 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. A maioria foi a favor da incorporação de carfilzomibe no SUS (97% via formulário técnico-científico e 100%). O principal benefício apontado nas contribuições técnico-científicas foi sobre a eficácia, aumento da sobrevida e qualidade de vida, além da disponibilidade de mais uma opção terapêutica e promoção da igualdade no tratamento nos sistemas público e privado de saúde. A empresa detentora do registro do medicamento atualizou o preço do medicamento, e consequentemente os valores do impacto orçamentário e avaliação econômica. No impacto orçamentário o valor ficou em R$ 95,3 milhões em cinco anos. Nas contribuições de experiência e opinião, a totalidade dos respondentes discordou da recomendação preliminar da Conitec. No âmbito das opiniões e experiências positivas, foi mencionada a necessidade de garantir o acesso ao carfilzomibe, especialmente por representar uma alternativa para pacientes recidivados e refratários. Também foi citada a eficácia da tecnologia. Como dificuldades, destacou-se a falta de acesso pelo SUS. Em relação a outros medicamentos, foram mencionados benefícios, mas, também, a eficácia limitada no caso de pacientes recidivados. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário da Conitec, em sua 112ª Reunião Ordinária, realizada no dia 31 de agosto de 2022, deliberaram por maioria simples, recomendar a não incorporação no SUS de carfilzomibe para o tratamento de pacientes com mieloma múltiplo recidivado ou refratário, que receberam terapia prévia, no SUS. Não houve apresentação de dados clínicos adicionais. Com o preço do medicamento atualizado, ainda assim não se mostrou custo-efetivo. Foi assinado o Registro de Deliberação nº 765/2022. DECISÃO: Não incorporar, no âmbito do Sistema Único de Saúde - SUS, o carfilzomibe para o tratamento de pacientes com mieloma múltiplo recidivado ou refratário, conforme a Portaria nº 107, publicada no Diário Oficial da União nº 184, seção 1, página 75, em 27 de setembro de 2022.

Economic Aspects in the Management of Diabetic Macular Edema in Italy.

Background: Diabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant. Methods: The analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison. Results: The increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years. Conclusions: To optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society.

Economic Value of Fosaprepitant-Containing Regimen in the Prevention of Chemotherapy-Induced Nausea and Vomiting in China: Cost-Effectiveness and Budget Impact Analysis.

Objective: The purpose of this study was to evaluate the cost-effectiveness and budget impact of fosaprepitant (FosAPR)-containing regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) from the Chinese payer's perspective. Methods: A decision tree model was established to measure the 5-day costs and health outcomes between the APR-containing regimen (aprepitant, granisetron, and dexamethasone) and FosAPR-containing regimen (fosaprepitant, granisetron, and dexamethasone). Clinical data were derived from a randomized, double-blind controlled trial on Chinese inpatients who received HEC. Quality-adjusted life-years (QALYs) were used to estimate the utility outcomes and the incremental cost-effectiveness ratio (ICER) was calculated to assess the economics of FosAPR. A static budget impact model was developed to assess the impact of FosAPR as a new addition to the National Reimbursement Drug List (NRDL) on the medical insurance fund within 3 years in Nanjing, China. Results: Compared with APR, FosAPR had a mean health-care savings of ¥121.56 but got a reduction of 0.0001815 QALY, resulting in an ICER of ¥669926.19 per QALY. Deterministic sensitivity analysis revealed that the cost of APR was the most influential factor to the ICER. The cost of FosAPR and the complete control rate of the delayed period also had a high impact on the results. According to the probabilistic analysis, the acceptability of FosAPR was more than 80% when the Chinese willingness-to-pay (WTP) was ¥215,999. FosAPR would lead to a 3-year medical insurance payment increase of ¥1.84 million compared with ¥1.49 million before FosAPR entered NRDL in Nanjing. The total budget increased with a cumulative cost of ¥694,829 and covered an additional 341 patients who benefited from FosAPR in Nanjing. Deterministic sensitivity analysis showed that the model of budget impact analysis was stable. Conclusion: FosAPR had a similar treatment effect to APR but was cost-effective in China at the current WTP threshold. The total budget of medical insurance payments of Nanjing slightly increased year by year after the inclusion of FosAPR. Its inclusion in the NRDL would be acceptable and also expand the coverage of patients who benefited from FosAPR.