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1.
Lancet Haematol ; 11(2): e101-e113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302221

RESUMO

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.


Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Pneumonia , Sepse , Adulto , Masculino , Feminino , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Lenalidomida/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Pneumonia/etiologia , Sepse/induzido quimicamente , Sepse/tratamento farmacológico
2.
Nat Commun ; 15(1): 1051, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316751

RESUMO

Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.


Assuntos
Anticorpos Monoclonais , COVID-19 , Humanos , Animais , Camundongos , SARS-CoV-2 , Microscopia Crioeletrônica , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus/genética
3.
Sci Rep ; 14(1): 3037, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321099

RESUMO

The use of tocilizumab for the management of COVID-19 emerged since it modulates inflammatory markers by blocking interleukin 6 receptors. Concerns regarding higher thrombosis risk while using tocilizumab were raised in the literature. The aim of this study is to investigate the association between tocilizumab therapy and the development of thromboembolic events in critically ill COVID-19 patients. A propensity score-matched, multicenter cohort study for critically ill adult patients with COVID-19. Eligible patients admitted to ICU between March 2020 and July 2021 were categorized into two sub-cohorts based on tocilizumab use within 24 h of ICU admission. The primary endpoint was to assess the incidence of all thrombosis cases during ICU stay. The secondary endpoints were 30-day mortality, in-hospital mortality, and the highest coagulation parameters follow-up (i.e., D-dimer, Fibrinogen) during the stay. Propensity score matching (1:2 ratio) was based on nine matching covariates. Among a total of 867 eligible patients, 453 patients were matched (1:2 ratio) using propensity scores. The thrombosis events were not statistically different between the two groups in crude analysis (6.8% vs. 7.7%; p-value = 0.71) and regression analysis [OR 0.83, 95% CI (0.385, 1.786)]. Peak D-dimer levels did not change significantly when the patient received tocilizumab (beta coefficient (95% CI): 0.19 (- 0.08, 0.47)), while there was a significant reduction in fibrinogen levels during ICU stay (beta coefficient (95% CI): - 0.15 (- 0.28, - 0.02)). On the other hand, the 30-day and in-hospital mortality were significantly lower in tocilizumab-treated patients (HR 0.57, 95% CI (0.37, 0.87), [HR 0.67, 95% CI (0.46, 0.98), respectively). The use of tocilizumab in critically ill patients with COVID-19 was not associated with higher thrombosis events or peak D-dimer levels. On the other hand, fibrinogen levels, 30-day and in-hospital mortality were significantly lower in the tocilizumab group. Further randomized controlled trials are needed to confirm our findings.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Trombose , Adulto , Humanos , Estudos de Coortes , SARS-CoV-2 , Estado Terminal , Tratamento Farmacológico da COVID-19 , Fibrinogênio , Estudos Retrospectivos
4.
Front Immunol ; 15: 1301329, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322266

RESUMO

Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes simplex virus (HSV) and occasionally cytomegalovirus (CMV). Sintilimab is an immune checkpoint inhibitor (ICI) that can enhance the body's anti-tumor immune response. However, treatment with ICIs may lead to reactivation of the VZV. Here, we present a case of ARN caused by VZV infection in a patient receiving sintilimab for cervical cancer. A 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer. Based on clinical manifestations, ophthalmological examination, and vitreous humor biopsy, the patient was diagnosed with acute retinal necrosis syndrome secondary to VZV. After receiving systemic antiviral and anti-inflammatory therapy, retinal necrosis lesions and visual function improved. In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction.


Assuntos
Anticorpos Monoclonais Humanizados , Herpes Simples , Síndrome de Necrose Retiniana Aguda , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Necrose Retiniana Aguda/diagnóstico , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico , Herpesvirus Humano 3
5.
Ups J Med Sci ; 1292024.
Artigo em Inglês | MEDLINE | ID: mdl-38327639

RESUMO

Background: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment. Methods: Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively. Results: Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively. Conclusions: The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.


Assuntos
Anticorpos Monoclonais Humanizados , Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Anticolesterolemiantes/uso terapêutico , Pró-Proteína Convertase 9/uso terapêutico , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de PCSK9 , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Suécia/epidemiologia , Resultado do Tratamento
6.
J Wound Care ; 33(Sup2a): xxviii-xxxi, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324423

RESUMO

Genital lymphoedema is a rare but debilitating and disfiguring complication of longstanding hidradenitis suppurativa (HS). Despite the existence of medical and surgical methods that offer varying success rates in a limited number of cases, no data exist about the use of complex decongestive therapy (CDT) in HS-related genital lymphoedema. This case report describes the treatment and outcome of a 56-year-old male patient with severe scrotal lymphoedema due to underlying HS (Hurley stage 3). The patient was unresponsive to various topical and systemic antibiotics and biological agents, including adalimumab and certolizumab pegol. When the patient was assessed, ixekizumab treatment for his HS was planned. He had progressive oedema in the genital area for two years with difficulty in wearing trousers and having sexual intercourse, and painful urination. CDT was recommended for three days a week concurrently with ixekizumab treatment. The patient and his wife were also educated about self-drainage techniques and skincare maintenance. After six sessions of CDT over 14 days, the patient demonstrated a significant reduction in scrotal measurements. He achieved a better scrotal contour, the degree of the buried penis was decreased, and urination was easier and painless. The findings of this case report showed that CDT was an easily applicable, practical and promising method that offered a rapid treatment response for HS-related genital lymphoedema.


Assuntos
Hidradenite Supurativa , Linfedema , Humanos , Masculino , Pessoa de Meia-Idade , Hidradenite Supurativa/terapia , Hidradenite Supurativa/cirurgia , Linfedema/terapia , Linfedema/cirurgia , Anticorpos Monoclonais Humanizados , Genitália
8.
RMD Open ; 10(1)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316489

RESUMO

OBJECTIVE: To evaluate the efficacy, immunogenicity and safety of the proposed biosimilar MSB11456 versus European Union (EU)-approved tocilizumab reference product in patients with rheumatoid arthritis (RA) in a multicentre, randomised, double-blind, multinational, parallel-group study (NCT04512001). METHODS: Adult patients with moderate-to-severe active RA and inadequate clinical response to ≥1 disease-modifying antirheumatic drug (synthetic or biologic) receiving methotrexate were randomised to receive 24 weekly subcutaneous 162 mg injections of either MSB11456 or EU-approved tocilizumab. Equivalence between treatments was considered if the 95% CI (European Medicines Agency)/90% CI (US Food and Drug Administration) for the difference in mean change from baseline to week 24 in Disease Activity Score-28 Joint Count with erythrocyte sedimentation rate (DAS28-ESR) between treatments was entirely within prespecified equivalence intervals (-0.6 to 0.6 and -0.6 to 0.5, respectively). At week 24, patients were rerandomised to continued treatment or MSB11456. Secondary efficacy endpoints to week 52, and safety and immunogenicity to week 55 were also evaluated. RESULTS: At week 24, the least squares mean difference in the change from baseline in DAS28-ESR between treatments was 0.01 (95% CI -0.19 to 0.22) in the 604 randomised patients. Similarity between treatments was shown for all other efficacy, safety and immunogenicity endpoints, including in patients who switched from EU-approved tocilizumab to MSB114466. CONCLUSIONS: Therapeutic equivalence was demonstrated for efficacy endpoints, and safety and immunogenicity analyses support the similarity of the two treatments. The results of this study strengthen the evidence that the proposed biosimilar MSB11456 and EU-approved tocilizumab exert similar clinical effects.


Assuntos
Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Estados Unidos , Adulto , Humanos , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos
9.
Nat Commun ; 15(1): 1043, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310086

RESUMO

Despite promising preclinical and earlier clinical data, a recent phase III trial on the anti-ß7 integrin antibody etrolizumab in Crohn's disease (CD) did not reach its primary endpoint. The mechanisms leading to this outcome are not well understood. Here we characterize the ß7+ T cell compartment from patients with CD in comparison to cells from individuals without inflammatory bowel disease. By flow cytometric, transcriptomic and functional profiling of circulating T cells, we find that triple-integrin-expressing (α4+ß7+ß1hi) T cells have the potential to home to the gut despite α4ß7 blockade and have a specific cytotoxic signature. A subset of triple-integrin-expressing cells readily acquires αE expression and could be co-stimulated via E-Cadherin-αEß7 interactions in vitro. Etrolizumab-s fails to block such αEß7 signalling at high levels of T cell stimulation. Consistently, in CD patients treated with etrolizumab, T cell activation correlates with cytotoxic signatures. Collectively, our findings might add one important piece to the puzzle to explain phase III trial results with etrolizumab, while they also highlight that αEß7 remains an interesting target for future therapeutic approaches in inflammatory bowel disease.


Assuntos
Anticorpos Monoclonais Humanizados , Doenças Inflamatórias Intestinais , Linfócitos T Citotóxicos , Humanos , Integrinas , Caderinas
10.
Nat Commun ; 15(1): 1029, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310101

RESUMO

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.


Assuntos
Anticorpos Monoclonais Humanizados , Quimioterapia de Indução , Neoplasias Nasofaríngeas , Piridinas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Quimioterapia de Indução/efeitos adversos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Quimiorradioterapia/efeitos adversos
11.
PLoS One ; 19(2): e0293264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300937

RESUMO

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.


Assuntos
Anticorpos Monoclonais Humanizados , Custos de Medicamentos , Neoplasias , Humanos , Anticorpos Monoclonais/uso terapêutico , Controle de Custos , Neoplasias/tratamento farmacológico
15.
J Dermatolog Treat ; 35(1): 2307489, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38305215

RESUMO

BACKGROUND: Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. OBJECTIVES: We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. METHODS: We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. RESULTS: At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50-80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. CONCLUSIONS: Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.


Assuntos
Anticorpos Monoclonais Humanizados , Compostos Heterocíclicos , Psoríase , Humanos , Japão , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Psoríase/terapia , Prurido/tratamento farmacológico , Prurido/etiologia
16.
Eur Rev Med Pharmacol Sci ; 28(2): 687-701, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305611

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1 inhibitor combined with transcatheter arterial chemoembolization (TACE), has been widely used in the treatment of HCC. However, there remains a contentious debate regarding the clinical value of the TACE and camrelizumab combination. This study seeks to investigate the efficacy and safety of this combination treatment regimen in patients with HCC. MATERIALS AND METHODS: The related studies were retrieved from four online databases, including Pubmed, Cochrane Library, EMBASE, and Web of Science, up to June 1, 2023. The selection of studies was based on screening of titles, abstracts, and full-texts. The primary efficacy outcomes included complete response (CR), objective response rate (ORR), and disease control rate (DCR), while safety outcomes evaluated all treatment-related adverse events (AEs). Additionally, secondary outcomes such as overall (OS) and progression-free survival (PFS) were extracted for further survival analysis. The quality of the included trials was assessed using the MINORS tool. Publication bias was evaluated through funnel plot and Egger's test. RESULTS: A total of 17 publications involving 1,377 cases were included. The pooled CR rate, ORR, and DCR of the patients treated with TACE plus camrelizumab had a pooled CR rate of 8% (95% CI: 0.01-0.15, p=0.03), ORR of 47% (95% CI: 0.42-0.52, p<0.00001) and DCR of 82% (95% CI: 0.77-0.88, p<0.00001), respectively. Compared with a control group that did not receive TACE or camrelizumab, the pooled RR of CR rate, ORR, and DCR were 1.61 (95% CI: 1.27-2.04, p<0.0001), 1.56 (95% CI: 1.19-2.05, p=0.001) and 1.55 (95% CI: 1.19-2.03, p=0.001), respectively. Besides, the combination regimen can prolong the OS (HR=2.60, 95% CI: 2.25-3.02, p<0.00001) and PFS (HR=4.90, 95% CI: 1.94-12.38, p=0.0008). However, the incidence of treatment-related AEs was relatively high (77%), with 29% for grade 3 AEs. The most common AEs observed were pain (47%), fever (46%), hepatic function abnormalities (44%), hypoalbuminemia (39%), and hypertension (37%). The combination treatment did not increase the incidence of AEs compared to the control group, except for the hand-foot skin reaction (RR=0.85, 0.74-0.97, p=0.01), hepatic encephalopathy (RR=4.29, 2.51-7.35, p<0.00001) and nausea (RR=1.35, 1.13-1.61, p=0.001). CONCLUSIONS: Combination therapy of TACE plus camrelizumab has shown notable clinical benefits, improved survival, and a manageable safety profile in patients with HCC, but it is essential to monitor and manage the specific toxicities, especially for the camrelizumab-related AEs.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/efeitos adversos , Recidiva Local de Neoplasia/terapia
17.
J Drugs Dermatol ; 23(2): 74-77, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306130

RESUMO

Early response to treatment with biologics, defined as Psoriasis Area and Severity Index (PASI) of 2 or less six months after initiation of therapy, seems to be associated with more stable psoriasis and a lower risk of flares and treatment discontinuation. This study aimed to identify markers that can predict early response to treatment with secukinumab in patients with plaque psoriasis. Treatment with secukinumab was initiated in 29 biologic-naive patients with plaque psoriasis (75.9% males). After six months, the patients were stratified as (1) PASI 2 or less responders or (2) PASI greater than 2 responders. Patients who achieved PASI 2 or less six months after initiation of secukinumab therapy already had significantly greater PASI reductions after the first month of therapy compared to those with PASI greater than 2 six months after treatment. Baseline blood monocyte counts significantly correlated with PASI, both before and six months after initiating secukinumab therapy. A lower monocyte count with a cutoff value set at less than 0.69 × 103/microL (based on ROC curve analysis) was found in multivariate analysis to be an independent factor for achieving PASI 2 or less six months after initiation of therapy with secukinumab (R2 = 0.7; beta = -0.67; P = 0.03). We showed that baseline monocyte count may be useful for predicting early response to secukinumab therapy in plaque psoriasis patients. Identifying such a marker may help clinicians choose the most appropriate biologics for patients with plaque psoriasis and help avoid the expense of switching from one biologic to another. J Drugs Dermatol. 2024;23(2):74-77.     doi:10.36849/JDD.7525.


Assuntos
Anticorpos Monoclonais Humanizados , Produtos Biológicos , Psoríase , Masculino , Humanos , Feminino , Anticorpos Monoclonais , Monócitos , Resultado do Tratamento , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Produtos Biológicos/uso terapêutico , Índice de Gravidade de Doença
19.
J Drugs Dermatol ; 23(2): 97-99, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306127

RESUMO

Paradoxical reactions to biologic agents used in the treatment of psoriasis are rare but have been reported with tumor necrosis factor (TNF) blockers and, more recently, with interleukin (IL)-17A inhibitors. Secukinumab, an IL-17A inhibitor, is an effective treatment for moderate-to-severe plaque psoriasis but has been implicated in the development or exacerbation of eczematous-like reactions in rare cases. We present a patient with a history of plaque psoriasis who developed an eczematous eruption after four months of secukinumab therapy, necessitating systemic intervention for adequate control. Five months after a loading dose of dupilumab, the patient appeared in the clinic with the return of classic, thick psoriatic plaques, affecting 15% BSA. The patient declined further treatment and was subsequently lost to follow-up despite multiple attempts to contact her. This case adds to the limited, but growing body of knowledge on IL-17 blocker-induced eczematous reactions and underscores the need for careful monitoring and prompt recognition of this adverse event in patients receiving this class of drugs. J Drugs Dermatol. 2024;23(2):97-99.     doi:10.36849/JDD.7639  .


Assuntos
Anticorpos Monoclonais Humanizados , Dermatite Atópica , Psoríase , Feminino , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica/induzido quimicamente , Psoríase/tratamento farmacológico , Resultado do Tratamento
20.
J Drugs Dermatol ; 23(2): 17-22, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306141

RESUMO

BACKGROUND: Biologics have shown promising outcomes in psoriasis clinical trials. However, there is a paucity of data exploring the potential differences in outcomes between self-identified racial groups. OBJECTIVE: To evaluate treatment response to ixekizumab in patients with psoriasis across different self-identified racial subgroups. METHODS: This study analyzed pooled data from 5 clinical studies (UNCOVER-1, UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) with patients of different self-identified racial subgroups, who were treated with an on-label dose of ixekizumab for psoriasis through 12 weeks. Treatment response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and static Physician’s Global Assessment response rates. Patient Global Assessment of Disease Severity, Itch Numeric Rating Scale, Skin Pain Visual Analog Scale, and Dermatology Life Quality Index were used to evaluate the patient-reported outcomes (PROs) and impact on quality of life (QoL). RESULTS: A total of 1825 ixekizumab-treated patients from 5 pooled studies were included. Consistent with the clinical outcomes from the overall population, all self-identified racial groups showed rapid improvement in PASI through Week 12, although the response was somewhat slower in American Indian/Alaska Native patients. Differences in PROs and QoL assessments were observed among racial groups, especially in patients who identified as Black/African American and American Indian/Alaska Native. CONCLUSION: Ixekizumab is effective through 12 weeks of treatment for psoriasis across different self-identified racial groups. Sample sizes for some racial groups were small (N≤12), therefore, further research is required to understand potential differences in psoriasis treatment with ixekizumab between various racial groups.J Drugs Dermatol. 2024;23(2):17-22.  doi:10.36849/JDD.7672.


Assuntos
Anticorpos Monoclonais Humanizados , Fármacos Dermatológicos , Psoríase , Humanos , Qualidade de Vida , Índice de Gravidade de Doença , Psoríase/tratamento farmacológico , Grupos Raciais , Resultado do Tratamento , Fármacos Dermatológicos/uso terapêutico
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