Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30.988
Filtrar
1.
J Coll Physicians Surg Pak ; 34(9): 1056-1060, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262005

RESUMO

OBJECTIVE: To determine the effectiveness of cyclosporin A (CSA) monotherapy in treating patients with non-severe aplastic anaemia (NSAA). STUDY DESIGN: A cross-sectional observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan, from January 2022 till December 2023. METHODOLOGY: A total of 51 patients of NSAA, classified as aplastic anaemia not satisfying criteria for severe and very severe disease as per Modified Camitta Criteria, were included. Results were evaluated in terms of survival rate (OS) and responses. Responses were assessed as complete response (CR), partial response (PR), overall response (ORR), and no response (NR) by using standard British Committee for standard Haematology (BCSH) response criteria at 3, 6, and 12 months. RESULTS: Out of 51 patients, 34 (67%) were males and 17 (33%) were females. Median age at the time of diagnosis was 25 (IQR 26) years. At follow-up of 12 months, OS was 86.3%. Overall response rates to cyclosporin monotherapy at 3, 6, and 12 months were 49%, 57%, and 59%, respectively. Baseline haemoglobin was associated with responses at 6 and 12 months and a significant association was found between transfusion dependency at 3, 6, and 12 months with overall survival (p = 0.01, 0.005, and 0.04, respectively). Responses at time-defined points also had significant impact on OS (3 months Plog-rank = 0.046, 6 months Plog-rank = 0.01, and 12 months Plog-rank = 0.008). CONCLUSION: Overall response rates at 3, 6, and 12 months indicate the potential of CSA as a viable treatment option, particularly in resource-constrained settings. Despite some patients experiencing treatment-related complications, CSA demonstrated a generally tolerable safety profile. KEY WORDS: Cyclosporin A, Non-severe aplastic anaemia, Survival rate, Response rate, Complete response, Partial response.


Assuntos
Anemia Aplástica , Ciclosporina , Imunossupressores , Humanos , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/mortalidade , Ciclosporina/uso terapêutico , Feminino , Masculino , Adulto , Estudos Transversais , Imunossupressores/uso terapêutico , Paquistão , Resultado do Tratamento , Adulto Jovem , Adolescente , Taxa de Sobrevida , Pessoa de Meia-Idade
2.
BMC Ophthalmol ; 24(1): 401, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251947

RESUMO

BACKGROUND: To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. METHODS: In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. RESULTS: A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. CONCLUSIONS: Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.


Assuntos
Ciclosporina , Síndromes do Olho Seco , Emulsões , Ácido Hialurônico , Imunossupressores , Soluções Oftálmicas , Lágrimas , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/fisiopatologia , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Soluções Oftálmicas/administração & dosagem , Feminino , Masculino , Estudos Prospectivos , Método Duplo-Cego , Pessoa de Meia-Idade , Adulto , Ácido Hialurônico/administração & dosagem , Lágrimas/metabolismo , Lágrimas/fisiologia , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Idoso
3.
Front Immunol ; 15: 1425076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221245

RESUMO

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores , Recidiva , Humanos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Adolescente , Adulto , Doença Enxerto-Hospedeiro/etiologia , Criança , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Adulto Jovem , Pré-Escolar , Pessoa de Meia-Idade , Resultado do Tratamento , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Transplante Homólogo , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Terapia de Imunossupressão/métodos , Estudos Retrospectivos , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem
4.
Support Care Cancer ; 32(10): 633, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230629

RESUMO

PURPOSE: Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. METHODS: A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. RESULTS: Participants aged 25-74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: "Transiting from an external obligation to a habit"; "Being in the middle between the negative and positive effects of the IMMs"; "Failure to systematically respect the rules"; and "Adopting personal strategies to become adherent". After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. CONCLUSIONS: MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients' MA to IMMs.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Imunossupressores , Adesão à Medicação , Pesquisa Qualitativa , Humanos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/psicologia , Pessoa de Meia-Idade , Masculino , Feminino , Adesão à Medicação/estatística & dados numéricos , Adulto , Idoso , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Doença Aguda , Administração Oral , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico
5.
J Drugs Dermatol ; 23(9): 795-806, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39231089

RESUMO

Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.


Assuntos
Urticária Crônica , Omalizumab , Humanos , Urticária Crônica/tratamento farmacológico , Urticária Crônica/diagnóstico , Omalizumab/uso terapêutico , Omalizumab/administração & dosagem , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem , Urticária/tratamento farmacológico , Urticária/diagnóstico
6.
Int J Pharm ; 664: 124593, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39168289

RESUMO

The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.


Assuntos
Antifúngicos , Biofilmes , Candida albicans , Ciclosporina , Sinergismo Farmacológico , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Voriconazol , Voriconazol/administração & dosagem , Voriconazol/farmacologia , Voriconazol/química , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Nanopartículas/química , Ciclosporina/administração & dosagem , Ciclosporina/farmacologia , Ciclosporina/química , Biofilmes/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Portadores de Fármacos/química , Polietilenoglicóis/química , Testes de Sensibilidade Microbiana , Ácido Láctico/química
7.
Ther Drug Monit ; 46(5): 563-566, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39194229

RESUMO

ABSTRACT: A 29-year-old Korean woman with chronic aplastic anemia presented with seizures due to cyclosporine-induced posterior reversible encephalopathy syndrome, caused by unpredictable oral cyclosporine (CS) accumulation and prolonged elimination. This case demonstrates the need to monitor CS drug levels with careful dose adjustments.


Assuntos
Anemia Aplástica , Ciclosporina , Imunossupressores , Humanos , Feminino , Adulto , Ciclosporina/uso terapêutico , Ciclosporina/efeitos adversos , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , República da Coreia , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Convulsões/induzido quimicamente
8.
Adv Ther ; 41(10): 3778-3791, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39196500

RESUMO

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.


Assuntos
Psoríase , Neoplasias Cutâneas , Humanos , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/epidemiologia , Ciclosporina/uso terapêutico , Ciclosporina/efeitos adversos , Fatores de Risco , Terapia PUVA/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Lasers Med Sci ; 39(1): 203, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088100

RESUMO

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.


Assuntos
Ciclosporina , Metaloproteinase 9 da Matriz , Disfunção da Glândula Tarsal , Soluções Oftálmicas , Lágrimas , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Ciclosporina/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Adulto , Estudos Retrospectivos , Disfunção da Glândula Tarsal/terapia , Disfunção da Glândula Tarsal/metabolismo , Lágrimas/metabolismo , Lágrimas/efeitos dos fármacos , Terapia de Luz Pulsada Intensa/métodos , Idoso , Terapia Combinada , Glândulas Tarsais/efeitos dos fármacos , Glândulas Tarsais/metabolismo , Glândulas Tarsais/efeitos da radiação , Túnica Conjuntiva/efeitos da radiação , Túnica Conjuntiva/efeitos dos fármacos
10.
Adv Exp Med Biol ; 1448: 601-609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39117842

RESUMO

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.


Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Humanos , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , COVID-19/imunologia , COVID-19/terapia , COVID-19/complicações , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2/imunologia , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/imunologia , Plasmaferese/métodos , Agentes de Imunomodulação/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Ciclosporina/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/terapia
11.
Cells ; 13(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39120282

RESUMO

Dry eye disease (DED) is caused by inflammation and damage to the corneal surface due to tear film instability and hyperosmolarity. Various eye drops are used to treat this condition. Each eye drop has different properties and mechanisms of action, so the appropriate drug should be used according to clinical phenotypes. This study aims to compare the therapeutic mechanisms of cyclosporine A (CsA) and diquafosol tetrasodium (DQS). An experimental in vivo/in vitro model of DED using hyperosmolarity showed decreased cell viability, inhibited wound healing, and corneal damage compared to controls. Treatment with cyclosporine or diquafosol restored cell viability and wound healing and reduced corneal damage by hyperosmolarity. The expression of the inflammation-related genes il-1ß, il-1α, and il-6 was reduced by cyclosporine and diquafosol, and the expression of Tnf-α, c1q, and il-17a was reduced by cyclosporine. Increased apoptosis in the DED model was confirmed by increased Bax and decreased Bcl-2 and Bcl-xl expression, but treatment with cyclosporine or diquafosol resulted in decreased apoptosis. Diquafosol increased NGF expression and translocation into the extracellular space. DED has different damage patterns depending on the progression of the lesion. Thus, depending on the type of lesion, eye drops should be selected according to the therapeutic target, focusing on repairing cellular damage when cellular repair is needed or reducing inflammation when inflammation is high and cellular damage is severe.


Assuntos
Córnea , Ciclosporina , Modelos Animais de Doenças , Síndromes do Olho Seco , Fator de Crescimento Neural , Nucleotídeos de Uracila , Cicatrização , Nucleotídeos de Uracila/farmacologia , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/genética , Cicatrização/efeitos dos fármacos , Animais , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Córnea/efeitos dos fármacos , Córnea/patologia , Córnea/metabolismo , Ciclosporina/farmacologia , Humanos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Polifosfatos/farmacologia , Camundongos
12.
Cutis ; 114(1): E31-E34, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39159346

RESUMO

A generalized fixed drug eruption (FDE) is an uncommon but potentially dangerous reaction to medication. In this case series, we present 1 patient with a generalized FDE and 2 patients with generalized bullous FDE that resolved with cyclosporine, though 1 patient required close monitoring in the intensive care unit. Immediate acceleration of care upon development and recognition of generalized bullous FDE is essential, as the mortality rate is similar to Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).


Assuntos
Toxidermias , Humanos , Toxidermias/etiologia , Toxidermias/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Síndrome de Stevens-Johnson/terapia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Idoso , Adulto , Assistência Ambulatorial , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem
14.
Ann Med ; 56(1): 2391019, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39155824

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.


High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.


Assuntos
Ciclosporina , Quimioterapia Combinada , Síndromes do Olho Seco , Humanos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Índice de Gravidade de Doença , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos
15.
Pharmacol Res Perspect ; 12(5): e1242, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39210688

RESUMO

Cyclosporin A (CsA), an immunosuppressive drug used in transplant recipients, inhibits graft rejection by binding to cyclophilins and competitively inhibiting calcineurin. While concerns about respiratory infections in immunosuppressed patients exist, contradictory data emerged during the COVID-19 pandemic, prompting investigations into CsA's impact on viral infections. This study explores CsA's antiviral effects on SARS-CoV-2 Omicron BA.1, Delta variants, and human parainfluenza virus 3 (HPIV3) using an ex vivo model of human airway epithelium (HAE). CsA exhibited a dose-dependent antiviral effect against the SARS-CoV-2 Delta variant, reducing viral load over 10 days. However, no significant impact was observed against SARS-CoV-2 Omicron or HPIV3, indicating a virus-specific effect. At high concentrations, CsA was associated with an increase of IL-8 and a decrease of IFNλ expression in infected and noninfected HAE. This study highlights the complexity of CsA's antiviral mechanisms, more likely involving intricate inflammatory pathways and interactions with specific viral proteins. The research provides novel insights into CsA's effects on respiratory viruses, emphasizing the need for understanding drug-virus interactions in optimizing therapeutic approaches for transplant recipients and advancing knowledge on immunosuppressive treatments' implications on respiratory viral infections. Limitations include the model's inability to assess T lymphocyte activation, suggesting the necessity for further comprehensive studies to decipher the intricate dynamics of immunosuppressive treatments on respiratory viral infections.


Assuntos
Antivirais , Ciclosporina , Imunossupressores , SARS-CoV-2 , Replicação Viral , Humanos , Ciclosporina/farmacologia , Replicação Viral/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Antivirais/farmacologia , Imunossupressores/farmacologia , Vírus da Parainfluenza 3 Humana/efeitos dos fármacos , Vírus da Parainfluenza 3 Humana/fisiologia , Mucosa Respiratória/virologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Carga Viral/efeitos dos fármacos , Interferons/farmacologia , Interferons/metabolismo , Interleucina-8/metabolismo , COVID-19/virologia , Relação Dose-Resposta a Droga
16.
Eur J Dermatol ; 34(4): 409-415, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39193678

RESUMO

The therapeutic arsenal for atopic dermatitis (AD) has increased in recent years. The use of biologics or Janus kinase inhibitors (JAKi) is advocated following failure or contraindication to cyclosporine (CSA), however, it is not known whether treatment with CSA can impact the response to biologics or JAKi. The aim of this study was to evaluate the effect of previous treatment with CSA on response to biologics or JAKi in patients with AD. This was a retrospective observational study including patients with AD treated for 16 weeks with a biologic or JAKi, who had previously received cyclosporine for at least four weeks. Thirty patients with AD, with a mean age of 25.07±9.91 years, of whom 18 (60%) were women, were included. The mean duration of CSA treatment was 43.39±31.32 weeks. After 16 weeks of biologic or JAKi treatment, 17 (56.7%) patients achieved EASI75. These patients had a higher cumulative dose of CSA (3,6815 vs.76,993.33 mg; p=0.022) and a longer treatment duration (24.5 vs.57.4 weeks; p=0.003). Additionally, a negative correlation was observed between cumulative dose of CSA and EASI or SCORAD at 16 weeks. Previous cumulative dose and longer duration of CSA treatment does not appear to have a negative impact on response to biologics and JAKi in patients with AD.


Assuntos
Produtos Biológicos , Ciclosporina , Dermatite Atópica , Inibidores de Janus Quinases , Humanos , Dermatite Atópica/tratamento farmacológico , Feminino , Ciclosporina/uso terapêutico , Estudos Retrospectivos , Masculino , Inibidores de Janus Quinases/uso terapêutico , Adulto , Produtos Biológicos/uso terapêutico , Adulto Jovem , Adolescente , Índice de Gravidade de Doença , Imunossupressores/uso terapêutico , Resultado do Tratamento
17.
Toxicol Appl Pharmacol ; 491: 117071, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159847

RESUMO

BACKGROUND: Different prophylactic protocols are available for preventing graft-versus-host disease (GVHD) after matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to compare the effectiveness of post-transplantation cyclophosphamide plus cyclosporine A (PT-CY/CSA) versus methotrexate plus CSA (MTX/CSA) as GVHD prophylaxis protocols in adult acute myeloid leukemia (AML) patients who received peripheral blood stem cells (PBSC) from fully matched donors. METHODS: The 1-year outcomes of 89 patients treated with PT-CY/CSA and 90 patients treated with MTX/CSA who had MSD allo-HCT for AML using unmanipulated mobilized PBSC were examined and compared. RESULTS: The cumulative incidence of acute GVHD at 100 days was considerably lower in the PT-CY/CSA group (4% vs 19.3%, p = 0.002), however there were no statistically significant difference in the cumulative incidence of chronic GVHD at 1-year (19.6% vs 37.4%, p = 0.053). Significant delays in neutrophil and platelet engraftments were reported in the PT-CY/CSA group (17 vs 12 days) and (13 vs 12 days), respectively (p < 0.001). The cumulative incidences of relapse (19.1% vs 13.7%, p = 0.470), overall survival (79.1% vs 77.3%, p = 0.986), non-relapse mortality (16.5% vs 16.8%, p = 0.837), and the GVHD and relapse-free survival (GRFS) (53.7% vs 46.6%, p = 0.478) did not differ statistically at 1-year. CONCLUSION: PT-CY/CSA demonstrated a significant decrease in the rate of acute GVHD. However, it was associated with engraftment delay.


Assuntos
Ciclofosfamida , Ciclosporina , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Metotrexato , Transplante de Células-Tronco de Sangue Periférico , Transplante Homólogo , Humanos , Doença Enxerto-Hospedeiro/prevenção & controle , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem , Masculino , Adulto , Feminino , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/terapia , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto Jovem , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Adolescente , Estudos Retrospectivos , Idoso
18.
Ann Hematol ; 103(9): 3483-3491, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39088061

RESUMO

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months.


Assuntos
Anemia Aplástica , Soro Antilinfocitário , Benzoatos , Hidrazinas , Imunossupressores , Pirazóis , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/mortalidade , Benzoatos/uso terapêutico , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Humanos , Hidrazinas/uso terapêutico , Hidrazinas/administração & dosagem , Hidrazinas/efeitos adversos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Imunossupressores/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Adulto Jovem , Idoso , Estudos Retrospectivos , Quimioterapia Combinada , Criança , Resultado do Tratamento , Índice de Gravidade de Doença , Pré-Escolar , Ciclosporina/uso terapêutico , Ciclosporina/administração & dosagem , China/epidemiologia , Taxa de Sobrevida
19.
J Pharm Biomed Anal ; 250: 116389, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39116584

RESUMO

Immunosuppressive drugs (ISDs) are given to avoid the allograft rejection after transplantation. The concentrations of ISDs should be closely monitored owing to their wide inter-individual variability in its pharmacokinetics and narrow therapeutic window. Currently, the whole blood concentration measurement is the major approach of therapeutic drug monitoring of clinical ISDs in organ transplantation. Its correlation with the efficacy of ISDs remains elusive. While the acute rejection after transplantation may occur even when whole-blood ISDs concentrations are within the target range. Since the site of action of ISDs are within the lymphocyte, direct measurement of drug exposure in target cells may more accurately reflect the clinical efficacy of ISDs. Although several methods have been developed for the peripheral blood mononuclear cells (PBMCs) extraction and drug concentration measurement, the complex pre-processing has limited the study of the relationship between intracellular ISDs concentrations and the occurrence of rejection. In this study, the extraction of ISDs in PBMCs was carried out by the liquid-liquid extraction with low temperature purification, without centrifugation. The lower limit of quantitation were 0.2 ng/mL for cyclosporine A, tacrolimus and sirolimus, 1.0 ng/mL for mycophenolic acid, and the within-run and between-run coefficient of variations were both less than 12.4 %. The calibration curves of mycophenolic acid had a linear range (ng/mL): 1.0-128.0 (r2 = 0.9992). The calibration curves of other three ISDs had a linear range (ng/mL): 0.2-20.48 (r2 > 0.9956). A total of 157 clinical samples were analyzed by the UPLC-MS/MS for ISDs concentration in blood or plasma ([ISD]blood or plasma) and the concentration within PBMCs ([ISD]PBMC). Although there was strong association between [ISD]PBMC and [ISD]blood or plasma, the large discrepancies between concentration within [ISD]blood or plasma and [ISD]PBMC were observed in a small proportion of clinical samples. The developed method with short analysis time and little amounts of blood sample can be successfully applied to therapeutic drug monitoring of ISDs in PBMCs for analysis of large numbers of clinical samples and is helpful to explore the clinical value of ISDs concentration in PBMCs.


Assuntos
Monitoramento de Medicamentos , Imunossupressores , Leucócitos Mononucleares , Extração Líquido-Líquido , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Extração Líquido-Líquido/métodos , Imunossupressores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/métodos , Tacrolimo/sangue , Ácido Micofenólico/sangue , Ácido Micofenólico/farmacocinética , Ciclosporina/sangue , Reprodutibilidade dos Testes , Limite de Detecção , Sirolimo/sangue , Espectrometria de Massa com Cromatografia Líquida
20.
Ren Fail ; 46(2): 2395451, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39212247

RESUMO

OBJECTIVE: This study aimed to compare the efficacy and safety of biologics, multitarget therapy, and standard therapy for the induction of lupus nephritis. METHODS: A systematic search of electronic databases (EMBASE, Web of Science, PubMed, Cochrane Library, and ClinicalTrials.gov) was conducted from inception to 30 August 2023. Our study included randomized controlled trials enrolling adult lupus nephritis patients treated with biologics or multitarget therapy, in comparison with standard therapy. The primary outcomes were the rates of complete renal remission (CRR) and serious adverse events (SAE). Stata 15.0 was used to conduct the network meta-analysis. RESULTS: Ten randomized controlled trials with a total of 1989 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, multitarget therapy, obinutuzumab, belimumab, and voclosporin therapy demonstrated superior efficacy in achieving complete renal remission. Among these options, multitarget therapy had the greatest effect (OR = 2.78, 95% CI = 1.81-4.26). Regarding safety, it was observed that there were no significant statistical differences among the various treatment options. Cluster analysis revealed that both obinutuzumab and belimumab exhibited good efficacy and safety. CONCLUSIONS: belimumab and obinutuzumab stood out as promising treatments due to their good performance in terms of efficacy and safety. Multitarget therapy may be the most effective approach for treating lupus nephritis. However, since the study population consists exclusively of Asian patients, further research is needed to verify the efficacy of multitarget therapy in lupus nephritis patients of non-Asian descent.


Assuntos
Anticorpos Monoclonais Humanizados , Produtos Biológicos , Nefrite Lúpica , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Ciclosporina , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Terapia de Alvo Molecular , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA