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1.
Cancer Med ; 13(9): e7232, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698679

RESUMO

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.


Assuntos
Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Mieloma Múltiplo , Talidomida , Talidomida/análogos & derivados , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Talidomida/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Intervalo Livre de Progressão , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos
4.
BMJ Case Rep ; 17(4)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627054

RESUMO

Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.


Assuntos
Mieloma Múltiplo , Talidomida/análogos & derivados , Humanos , Mieloma Múltiplo/patologia , Cloridrato de Bendamustina/uso terapêutico , Dexametasona/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Fígado/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
Drug Dev Res ; 85(3): e22191, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685610

RESUMO

Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.


Assuntos
Sistemas de Liberação de Medicamentos , Géis , Lecitinas , Psoríase , Talidomida , Talidomida/análogos & derivados , Psoríase/tratamento farmacológico , Lecitinas/química , Animais , Camundongos , Talidomida/administração & dosagem , Talidomida/química , Talidomida/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos dos fármacos , Administração Cutânea , Administração Tópica , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Imiquimode/administração & dosagem , Masculino
7.
Genes (Basel) ; 15(3)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38540428

RESUMO

Moderate-to-severe psoriasis (Ps) treatment includes systemic drugs and biological agents. Apremilast, a small molecule primarily metabolized by cytochrome CYP3A4, modulates the immune system by specifically inhibiting phosphodiesterase type 4 (PDE4) isoforms and is currently used for the treatment of Ps and psoriatic arthritis (PsA). Clinical trials and real-world data showed variable efficacy in response among Ps patients underlying the need for personalized therapy. This study implements a candidate-gene and a network-based approach to identify genetic markers associated with apremilast response in forty-nine Greek Ps patients. Our data revealed an association of sixty-four SNPs within or near PDE4 and CYP3A4 genes, four SNPs in ncRNAs ANRIL, LINC00941 and miR4706, which influence the abundance or function of PDE4s, and thirty-three SNPs within fourteen genes whose protein products either interact directly with PDE4 proteins or constitute components of the cAMP signaling pathway which is modulated by PDE4s. Notably, fifty-six of the aforementioned SNPs constitute eQTLs for the respective genes in relevant to psoriasis tissues/cells implying that these variants could be causal. Our analysis provides a number of novel genetic variants that, upon validation in larger cohorts, could be utilized as predictive markers regarding the response of Ps patients to apremilast treatment.


Assuntos
Artrite Psoriásica , Psoríase , Talidomida/análogos & derivados , Humanos , Artrite Psoriásica/induzido quimicamente , Artrite Psoriásica/tratamento farmacológico , Citocromo P-450 CYP3A , Psoríase/tratamento farmacológico , Psoríase/genética , Talidomida/uso terapêutico , Talidomida/efeitos adversos
8.
Cell Transplant ; 33: 9636897241237049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483119

RESUMO

Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague-Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous [i.v.]) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.


Assuntos
Lesões Encefálicas Traumáticas , Doenças Neuroinflamatórias , Talidomida/análogos & derivados , Ratos , Animais , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Estresse Oxidativo , Citocinas/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças
9.
Int J Pharm ; 655: 124026, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38518872

RESUMO

Apremilast (APR) is a potent anti-psoriatic agent that inhibits the phosphodiesterase 4 enzyme. Due to the poor oral bioavailability and associated systemic side effects the clinical applicability of APR has been constrained. Nanotechnology-based carrier system presents a novel option to increase the efficacy of the topical treatment of APR. The current investigation deals with the development of fatty acid-surfactant conjugate-based hybrid mixed micellar gel (HMMG) for the topical delivery of APR. The developed micelles exhibited an average size of 83.59 ± 4.46 nm, PDI of 0.239 ± 0.047, % entrapment efficiency of âˆ¼ 94.78 ± 3.98 %, with % practical drug loading of ∼11.37 ± 3.14 %. TEM analysis revealed the spherical shape of micelles. The hybrid micelles were further loaded in a carbopol®934P gel base for ease of application. Ex vivo permeation study revealed enhanced permeation and âˆ¼ 38-fold higher retention in deeper layers of skin from a hybrid micellar gel. In vivo, assessment demonstrated augmented efficacy of APR-HMMG as compared to 0.1 % betamethasone valerate. Also, APR-HMMG showed no sign of irritation, suggesting superior safety as a topical application. Thus, the proposed formulation strategy represents a viable avenue for enhancing the therapeutic efficacy of various anti-psoriatic moieties.


Assuntos
Psoríase , Surfactantes Pulmonares , Talidomida/análogos & derivados , Humanos , Micelas , Ácidos Graxos , Portadores de Fármacos , Tensoativos , Pele , Géis , Psoríase/tratamento farmacológico , Tamanho da Partícula
10.
Skin Res Technol ; 30(3): e13642, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454597

RESUMO

AIMS AND OBJECTIVES: The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions. METHOD: Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles. RESULTS: In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%). CONCLUSION: Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.


Assuntos
Azetidinas , Hipopigmentação , Purinas , Pirazóis , Sulfonamidas , Talidomida/análogos & derivados , Vitiligo , Humanos , Metotrexato/uso terapêutico , Azatioprina/uso terapêutico , Vitiligo/tratamento farmacológico , Vitiligo/patologia , Ácido Micofenólico/uso terapêutico , Minociclina/uso terapêutico , Alefacept/uso terapêutico , Ciclosporina/uso terapêutico , Corticosteroides , Sinvastatina/uso terapêutico , Zinco/uso terapêutico
11.
Am J Clin Dermatol ; 25(3): 347-358, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438782

RESUMO

BACKGROUND: The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. OBJECTIVE: The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks. RESULTS: The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome. CONCLUSION: Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.


Assuntos
Produtos Biológicos , Metanálise em Rede , Psoríase , Talidomida/análogos & derivados , Psoríase/tratamento farmacológico , Humanos , Produtos Biológicos/uso terapêutico , Resultado do Tratamento , Fármacos Dermatológicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Anticorpos Monoclonais Humanizados/uso terapêutico
12.
Adv Ther ; 41(4): 1594-1605, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402373

RESUMO

INTRODUCTION: Psoriasis is a chronic inflammatory condition that can significantly impact the quality of life (QoL), regardless of the level of skin involvement. Apremilast is indicated for the treatment of moderate to severe psoriasis. Real-world data regarding the impact of apremilast on patient-reported outcomes in clinical practice in the Netherlands is lacking. METHODS: The prospective, multicenter observational Apremilast in Real-Life Psoriasis Treatment (APRIL) study enrolled patients ≥ 18 years old with moderate to severe plaque psoriasis receiving apremilast in clinical practice in the Netherlands. Patients were followed-up for 12 months, with assessments scheduled at 6 and 12 months. The primary outcome was Dermatology Life Quality Index (DLQI) response (score ≤ 5 or ≥ 5-point improvement from baseline) at 6 months. Secondary patient-reported outcomes included EQ-5D and skin-specific parameters; exploratory outcomes were Patient Benefit Index (PBI) and Work Productivity and Activity Impairment (WPAI). RESULTS: Of the 155 patients enrolled (February 2016-June 2019), 153 received apremilast; 69 (45%) and 39 (26%) continued treatment at 6 and 12 months, respectively. Psoriasis in special areas was common (scalp, 65%; nail, 51%; palmoplantar, 27%). Most patients (92%) had received prior systemic antipsoriatic therapies. Of the 151 patients with a baseline DLQI value, 56 (37%) achieved DLQI response at 6 months. Mean (standard deviation) PBI scores were 3.5 (1.2) and 3.8 (1.1) at 6 and 12 months, respectively. Improvements in DLQI, EQ-5D, and WPAI scores and disease signs and symptoms, including itch and special areas, were observed at 6 and 12 months. Adverse events were consistent with the known safety profile. CONCLUSIONS: In the Netherlands, patients with moderate to severe psoriasis receiving apremilast for up to 12 months reported improved disease-related QoL, skin involvement, and patient-reported outcomes. These data add to the growing body of evidence demonstrating apremilast is an effective treatment for psoriasis, itch, and special areas (scalp and palms). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02652494.


Assuntos
Psoríase , Qualidade de Vida , Talidomida , Adolescente , Humanos , Países Baixos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Talidomida/análogos & derivados , Resultado do Tratamento
13.
Leuk Lymphoma ; 65(4): 481-492, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38345269

RESUMO

Nearly all patients with multiple myeloma eventually relapse or become refractory to treatment. Lenalidomide is increasingly administered in the frontline until disease progression or intolerance to therapy, resulting in the need for highly effective, lenalidomide-sparing options. In this study, carfilzomib plus daratumumab and dexamethasone were evaluated against lenalidomide-sparing, pomalidomide-containing triplets using matching-adjusted indirect comparison in the absence of head-to-head data. The analyses utilized long-term follow-up data from the CANDOR study (NCT03158688). Treatment with carfilzomib, daratumumab, and dexamethasone resulted in significantly longer progression-free survival (hazard ratio 0.60 [95% confidence interval: 0.37, 0.88])vs. pomalidomide plus bortezomib and dexamethasone, and numerically longer progression-free survival (hazard ratio 0.77 [95% confidence interval: 0.50, 1.08]) vs. daratumumab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma and previous lenalidomide exposure, the majority of whom were lenalidomide refractory. Carfilzomib plus daratumumab and dexamethasone offers a highly effective, lenalidomide-sparing treatment option for this population.


Assuntos
Anticorpos Monoclonais , Mieloma Múltiplo , Oligopeptídeos , Talidomida , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Talidomida/análogos & derivados
14.
Lancet Haematol ; 11(3): e216-e227, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423700

RESUMO

BACKGROUND: Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint. METHODS: In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS-quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models. FINDINGS: Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55-68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0-26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges' g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS. INTERPRETATION: Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma. FUNDING: 2seventy bio and Celgene, a Bristol Myers Squibb Company.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Talidomida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida/psicologia , Receptores de Antígenos Quiméricos/uso terapêutico , Talidomida/análogos & derivados , Idoso
16.
Eur J Haematol ; 112(6): 975-983, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38382632

RESUMO

OBJECTIVES AND METHODS: We conducted a multicenter retrospective study to analyze the safety and efficacy of DPd versus DKd in daratumumab naïve RRMM patients treated in real-world practice. RESULTS: A total of 187 patients with RRMM were included in the analysis; 128 patients received DPd, and 59 patients received DKd. A vast majority (80%) of patients had lenalidomide refractory disease and nearly 50% had bortezomib refractory disease. The overall response and complete response rates were 76% and 34% in the DPd group versus 80% and 51% in the DKd group, respectively. With a median follow up of 36 months for the entire patient population, median PFS and OS in the DPd versus DKd groups were 12, 12, 37, and 35 months, respectively. The most common grade 3+ adverse events in the DPd versus DKd groups were neutropenia (32% vs. 7%), anemia (14% vs. 10%), thrombocytopenia (13% vs. 15%), and cardiovascular events (4% vs. 15%), respectively. Both DPd and DKd appeared to be a safe and effective treatment options for RRMM. CONCLUSIONS: While there were more cytopenias associated with DPd and more cardiovascular side effects with DKd, there were no significant differences in the survival outcomes with these two regimens.


Assuntos
Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Oligopeptídeos , Talidomida , Talidomida/análogos & derivados , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/diagnóstico , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Pessoa de Meia-Idade , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Talidomida/efeitos adversos , Estudos Retrospectivos , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Resultado do Tratamento , Idoso de 80 Anos ou mais , Adulto , Recidiva , Retratamento
17.
Laryngorhinootologie ; 103(5): 352-357, 2024 May.
Artigo em Alemão | MEDLINE | ID: mdl-38330997

RESUMO

Behçet's syndrome (BS, synonym: Behçet's disease, or Adamantiades-Behçet's disease, ABD) is classified as a vasculitis of variable vessel size and can manifest itself in both arterial and venous vessels. Its extensive and at the same time interindividually very different clinical picture is not uncommon a challenge, both with regard to the diagnosis of this rheumatic systemic disease, which is rather rare in our latitudes, and its therapeutic options. In addition to the four cardinal symptoms of recurrent oral aphthae, genital aphthae, skin and eye lesions, the clinical picture offers numerous other manifestations which often require interdisciplinary cooperation. In addition to the above mentioned ocular involvement, which can still lead to blindness if inadequately treated, this is especially true for intestinal and cerebral manifestations as well as for large vessel vasculitis.A final revision of the European League Against Rheumatism recommendations for the management of Behcet's syndrome (EULAR) was made in 2018, and the recommendations are now established internationally as an important treatment guide. Therapy is based on the leading organ involvement. After adalimumab received approval for the treatment of posterior ocular involvement in 2016, another agent, apremilast, became available in 2020. The drug is recommended for the treatment of recurrent oral aphthae in adult Behçet's patients requiring systemic therapy. Nevertheless, there is a further need for new drugs.This article aims to highlight recent findings in the areas of epidemiology, immunopathogenesis & genetics, clinical findings, and therapy, with an emphasis on clinical relevance.


Assuntos
Síndrome de Behçet , Talidomida/análogos & derivados , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/terapia , Síndrome de Behçet/tratamento farmacológico , Humanos , Talidomida/uso terapêutico , Adalimumab/uso terapêutico , Colaboração Intersetorial
18.
Expert Rev Hematol ; 17(4-5): 127-134, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38421372

RESUMO

BACKGROUND: To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM). METHODS: Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes. RESULTS: This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%). CONCLUSIONS: Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42023420644.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Talidomida , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Humanos , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva , Resultado do Tratamento
20.
JAMA Dermatol ; 160(3): 334-340, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38294794

RESUMO

Importance: Laboratory testing for the presence of tuberculosis, hepatitis, and other conditions before starting most systemic immunomodulatory agents is recommended in patients with chronic inflammatory skin diseases (CISD) but current testing patterns in the US are unclear. Objective: To determine the prevalence of pretreatment testing that is recommended for patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis). Design, Setting, and Participants: This descriptive analysis of US commercial insurance claims databases from December 31, 2002, to December 31, 2020, included adult patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis) who started an immunomodulatory agent, including methotrexate, tumor necrosis factor α inhibitors, interleukin (IL)-17Ai, ustekinumab, IL-23i, dupilumab, or apremilast. Main Outcomes and Measures: The proportion of patients who underwent the screening tests as suggested by professional societies-including for tuberculosis, hepatitis, and liver function; complete blood cell counts; and lipid panels-were determined within 6 months before and during 2 years after treatment start. Results: A total of 122 308 patients with CISDs (median [IQR] age, 49 [38-58] years; 63 663 [52.1%] male) starting systemic immunomodulatory treatment in the US were included. Treatment for patients with CISDs comprised methotrexate (28 684), tumor necrosis factor α inhibitors (40 965), ustekinumab (12 841), IL-23i (6116), IL-17Ai (9799), dupilumab (7787), or apremilast (16 116). Complete blood cell count was the most common test, performed in 41% (3161/7787) to 69% (19 659/28 684) of individuals before initiation across treatments. Between 11% (889/7787) and 59% (3613/6116) of patients had tuberculosis screening within 6 months before treatment, and 3% (149/4577) to 26% (1559/6097) had updated tests 1 year later. Between 13% (1006/7787) and 41% (16 728/40 965) had hepatitis panels before treatment. Low pretreatment testing levels before apremilast (15% [2331/16 116] to 45% [7253/16 116]) persisted a year into treatment (9% [816/8496] to 36% [2999/8496]) and were similar to dupilumab (11% [850/7787] to 41% [3161/7787] vs 3% [149/4577] to 25% [1160/4577]). Conclusions and Relevance: In this descriptive analysis of patients with CISDs starting systemic immunomodulatory treatment in the US, less than 60% received the recommended pretreatment testing. Additional research is required to understand whether variations in testing affect patient outcomes.


Assuntos
Dermatite Atópica , Hepatite , Hidradenite Supurativa , Psoríase , Talidomida/análogos & derivados , Tuberculose , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Ustekinumab/uso terapêutico , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa , Agentes de Imunomodulação , Prevalência , Psoríase/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Tuberculose/induzido quimicamente
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