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1.
RMD Open ; 9(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36593080

RESUMO

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk-benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case.


Assuntos
Dermatomiosite , Imunossupressores , Humanos , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/efeitos adversos , Doenças Pulmonares Intersticiais/epidemiologia
2.
Lupus Sci Med ; 10(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631164

RESUMO

BACKGROUND: Recent guidelines for SLE recommend using a hydroxychloroquine (HCQ) dose less than 5.0 mg/kg/day to reduce the risk of retinopathy. To determine if this dose reduction would have an impact on the clinical course of SLE, we compared flare incidence in a cohort of patients with SLE treated with two different oral HCQ dosages (≤5 mg/kg/day or >5 mg/kg/day). As a secondary analysis, we compared HCQ blood levels between the two different oral dosages, and evaluated the frequency of non-adherence in patients with SLE treated with HCQ. METHODS: We identified a cohort of patients with SLE taking HCQ for at least 6 months and followed for 24 months. At study entry and 6 months later, a blood venous sample was taken to measure HCQ blood levels by liquid chromatography. Incidence of new SLE flares after recruitment was put in relation to daily HCQ dose and mean HCQ blood levels. Cox regression analysis served to identify factors associated with SLE flares. RESULTS: 83 patients were enrolled. We observed 11 (16%) flares that developed in mean 14.8 months of follow-up. The difference in terms of flare rate and mean HCQ blood levels between the two oral dosages was not statistically significant. There was a trend (p=0.08) for high HCQ dose being associated with a lower flare rate. At Cox analysis, higher HCQ blood levels and older age at baseline were protective against flare occurrence, while concomitant immunosuppressant therapy showed significant positive association. HCQ blood levels did not correlate with prescribed HCQ dose. CONCLUSION: Patients with low oral HCQ dosage tend to have more flares, although the difference was not statistically significant. Higher HCQ blood levels were protective against flare occurrence. The risks and benefits must be balanced in choosing HCQ dose.


Assuntos
Antirreumáticos , Lúpus Eritematoso Sistêmico , Doenças Retinianas , Humanos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Antirreumáticos/efeitos adversos , Imunossupressores/efeitos adversos , Doenças Retinianas/induzido quimicamente
3.
Ther Drug Monit ; 45(1): 102-109, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36624577

RESUMO

PURPOSE: Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence. METHODS: A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models. RESULTS: The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43-2.10, P < 0.001)]. CONCLUSION: This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.


Assuntos
Diabetes Mellitus , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Tacrolimo/efeitos adversos , Imunossupressores/efeitos adversos , Diabetes Mellitus/induzido quimicamente
4.
PLoS One ; 18(1): e0278894, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662740

RESUMO

INTRODUCTION: Calcineurin inhibitors constitute a cornerstone of immunosuppressive therapy in kidney transplant recipients. There are two main formulations of tacrolimus (Tac) which exhibit a prolonged-release mode of action: Advagraf® (MR-4) and Envarsus® (LCPT). However, they are not bioequivalent. Data comparing both once-daily prolonged-release formulations of Tac are insufficient. OBJECTIVE: The aim of the study was to compare safety and efficacy profiles of once-daily LCPT and MR-4 formulations of tacrolimus in adult kidney transplant recipients. PATIENTS AND METHODS: An observational, cohort single-center study was performed. One hundred fifteen kidney transplant recipients transplanted between 2016 and 2019 were enrolled to the study (59 vs 56, Envarsus® vs Advagraf®, respectively). Safety and efficacy profiles were assessed. RESULTS: Patient and graft survival at 12 and 24 months did not differ between the groups. There were no significant differences in serum creatinine at any timepoint. C/D ratio in the LCPT group was significantly higher at 12 and 24 months. Sepsis occurrence was more frequent in MR-4 group at 12 months. CONCLUSION: Both prolonged-release formulations of tacrolimus are safe and effective in immunosuppressive therapy in kidney transplant recipients.


Assuntos
Transplante de Rim , Tacrolimo , Adulto , Humanos , Tacrolimo/efeitos adversos , Imunossupressores/efeitos adversos , Seguimentos , Rejeição de Enxerto , Transplantados , Preparações de Ação Retardada
5.
Rev Neurol ; 76(s01): S1-S6, 2023 Jan 31.
Artigo em Espanhol | MEDLINE | ID: mdl-36683265

RESUMO

INTRODUCTION: Multiple sclerosis is a chronic neurological disease with numerous disease-modifying treatments available, including dimethyl fumarate (DMF), a first-line therapy for relapsing-remitting multiple sclerosis. Although rates of discontinuation of DMF are generally low in clinical trials, non-adherence to treatment is associated with poorer clinical outcomes. Assessing real-world adherence and predictive factors is critical to be able to improve clinical outcomes for patients. This study evaluated adherence to DMF over 24 months in a cohort of patients treated in a Portuguese healthcare centre. PATIENTS AND METHODS: A prospective, non-interventional, single-centre study with 24 months' follow-up was conducted. The study included adult patients with relapsing-remitting multiple sclerosis treated with DMF in routine clinical practice. Adherence to DMF was calculated and patients were considered to have adhered if the value was above 80%. Clinical and socio-demographic variables were compared between groups. RESULTS: Of the 80 patients included, 74% were women, with a mean age of 39 years and a mean age of 32 years at diagnosis. Twenty-six patients had not received any previous treatment. Adherence varied between 93, 82 and 87.5% at 6, 12 and 24 months, respectively. No differences were found between patients who had not received any prior treatment and those who had been treated. CONCLUSION: This real-world analysis showed significant adherence to DMF treatment by Portuguese patients over a period of two years. However, these results must be interpreted in the light of the substantial changes in outpatient consultations and the various periodic restrictions due to the COVID-19 pandemic, which had an important effect on patient follow-up and data collection.


TITLE: Adhesión real al dimetilfumarato en pacientes con esclerosis múltiple remitente-recurrente.Introducción. La esclerosis múltiple es una enfermedad neurológica crónica con numerosos tratamientos modificadores de la enfermedad disponibles, incluido el dimetilfumarato (DMF), una terapia de primera línea para la esclerosis múltiple remitente-recurrente. Aunque las tasas de discontinuación del DMF suelen ser bajas en los ensayos clínicos, la falta de adhesión al tratamiento se asocia con peores resultados clínicos. Evaluar la adhesión en el mundo real y los factores predictivos es fundamental para mejorar los resultados clínicos de los pacientes. Este estudio evaluó la adhesión al DMF durante 24 meses en una cohorte de pacientes tratados en un centro portugués. Pacientes y métodos. Estudio prospectivo no intervencionista, de un solo centro, con un seguimiento de 24 meses. El estudio incluyó a pacientes adultos con esclerosis múltiple remitente-recurrente tratados con DMF en la práctica clínica habitual. Se calculó la adhesión al DMF y se consideró que los pacientes eran adherentes si el valor estaba por encima del 80%. Se compararon variables clínicas y sociodemográficas entre grupos. Resultados. De los 80 pacientes incluidos, el 74% eran mujeres, con una edad media de 39 años y una edad media en el momento del diagnóstico de 32 años. Veintiséis pacientes no habían recibido tratamiento previo. La adhesión varió entre el 93, el 82 y el 87,5% a los 6, 12 y 24 meses, respectivamente. No se encontraron diferencias entre los pacientes que no habían recibido tratamiento previo y los que sí lo habían recibido. Conclusión. Este análisis en el mundo real mostró una adhesión significativa al tratamiento con DMF durante dos años por parte de los pacientes portugueses. No obstante, estos resultados deben interpretarse considerando los cambios sustanciales en las consultas externas y las diversas restricciones periódicas debidas a la pandemia de COVID-19, que afectaron en gran medida al seguimiento de los pacientes y a la recopilación de datos.


Assuntos
COVID-19 , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Humanos , Feminino , Masculino , Fumarato de Dimetilo/uso terapêutico , Fumarato de Dimetilo/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Pandemias , Estudos Prospectivos
6.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(1): 49-53, jan. 2023. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-214476

RESUMO

En dermatología es frecuente el uso de inmunosupresores e inmunomoduladores, algunos de los cuales pueden predisponer al desarrollo de enfermedad grave por SARS-CoV-2. Las nuevas terapias antivirales frente al SARS-CoV-2 han demostrado reducir la progresión a neumonía por COVID-19 grave en pacientes susceptibles. El pasado 23 de mayo, la Agencia Española de Medicamentos y Productos Sanitarios publicó la última actualización sobre los criterios para la priorización en el acceso precoz a estos fármacos debido a su limitada disponibilidad. En esta guía práctica revisamos los pacientes dermatológicos que en caso de contraer COVID-19 leve-moderada pueden beneficiarse de los nuevos antivirales, así como su indicación (AU)


Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology (AU)


Assuntos
Humanos , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Imunossupressores/efeitos adversos , Dermatopatias/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Suscetibilidade a Doenças/induzido quimicamente , Imunomodulação
7.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(1): T49-T53, jan. 2023. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-214477

RESUMO

Immunosuppressants and immunomodulators are widely used in dermatology. Some of these drugs, however, can increase the risk of severe COVID-19. New antivirals against SARS-CoV-2 have been shown to reduce progression to COVID-19 pneumonia in susceptible patients, but their availability is limited. On May 23, 2022, the Spanish Agency for Medicines and Medical Devices (AEMPS) updated its priority eligibility criteria for SARS-CoV-2 antiviral therapy. In this practical guide, we review the indications for these new drugs and provide guidance on which patients with mild to moderate COVID might benefit from their use in dermatology (AU)


En dermatología es frecuente el uso de inmunosupresores e inmunomoduladores, algunos de los cuales pueden predisponer al desarrollo de enfermedad grave por SARS-CoV-2. Las nuevas terapias antivirales frente al SARS-CoV-2 han demostrado reducir la progresión a neumonía por COVID-19 grave en pacientes susceptibles. El pasado 23 de mayo, la Agencia Española de Medicamentos y Productos Sanitarios publicó la última actualización sobre los criterios para la priorización en el acceso precoz a estos fármacos debido a su limitada disponibilidad. En esta guía práctica revisamos los pacientes dermatológicos que en caso de contraer COVID-19 leve-moderada pueden beneficiarse de los nuevos antivirales, así como su indicación (AU)


Assuntos
Humanos , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Imunossupressores/efeitos adversos , Dermatopatias/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Suscetibilidade a Doenças/induzido quimicamente , Imunomodulação
8.
Schweiz Arch Tierheilkd ; 165(1): 53-58, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36562746

RESUMO

INTRODUCTION: Cyclosporine is a potent immunosuppressive agent used in veterinary medicine to treat a variety of inflammatory or immune mediated conditions. Many adverse effects are associated with this medication, however most of them rarely occur. A 5-year-old, female intact French bulldog was presented with multiple, multifocally distributed, severe hyperkeratotic and papillomatous/verrucous plaques. The dog was on long-term immunosuppressive treatment with cyclosporine for meningoencephalitis of unknown origin (MUO). It had an history of atopic dermatitis and calcinosis cutis. A papillomavirus infection was excluded by polymerase chain reaction (PCR), and histopathologic analysis revealed a chronic lymphoplasmacytic non-specific dermatitis, perifolliculitis and periadnexitis and focal folliculitis with papillomatous epidermal hyperplasia and orthokeratotic hyperkeratosis. The diagnosis of "cyclosporine-induced epidermal hyperplasia with secondary pyoderma" was made. Cyclosporine was discontinued and as an alternative mycophenolate mofetil was started to control the MUO. An antimicrobial treatment was prescribed for three weeks. After four months, the skin lesions had healed completely. To date after 2 years, the dog is still in remission. The occurrence of hyperplastic lesions associated with cyclosporine therapy have already been described in previous reports. Most of them resemble those of psoriasiform lichenoid dermatitis, although papilloma virus may be detected in some instances. The dog of the present case showed some peculiarities in the histopathological findings, and a papillomavirus involvement was ruled out with PCR. Like observed in a previous report, there was no correlation between cyclosporine blood level and the severity of dermatological changes. A discontinuation of cyclosporine resulted in complete healing in 4 months. This case highlights the importance of regular monitoring and follow-ups in patients on immunosuppressive therapy. Even rare side effects should always be considered in these cases.


INTRODUCTION: La cyclosporine est un puissant agent immunosuppresseur utilisé en médecine vétérinaire pour traiter une variété de conditions inflammatoires ou à médiation immunitaire. De nombreux effets indésirables sont associés à ce médicament, mais la plupart d'entre eux se produisent rarement. Un bouledogue français intact, âgé de 5 ans, a été présenté avec de multiples plaques hyperkératosiques et papillomateuses/verruqueuses sévères, réparties de manière multifocale. Le chien suivait un traitement immunosuppresseur à long terme à base de cyclosporine pour une méningo-encéphalite d'origine inconnue (MUO). Il avait des antécédents de dermatite atopique et de calcinosis cutis. Une infection à papillomavirus a été exclue par réaction en chaîne par polymérase (PCR) et l'analyse histopathologique a révélé une dermatite chronique lymphoplasmocytaire non spécifique, une périfolliculite et une périannexite ainsi qu'une folliculite focale avec hyperplasie épidermique papillomateuse et hyperkératose orthokératosique. Le diagnostic d'¼hyperplasie épidermique induite par la cyclosporine avec pyodermie secondaire¼ a été posé. La cyclosporine a été stoppée et on a commencé à administrer du mycophénolate mofétil comme alternative pour contrôler l'OMU. Un traitement antimicrobien a été prescrit pendant trois semaines. Après quatre mois, les lésions cutanées étaient complètement guéries. À ce jour, après deux ans, le chien est toujours en rémission. L'apparition de lésions hyperplasiques associées au traitement par la cyclosporine a déjà été décrite dans des rapports précédents. La plupart d'entre elles ressemblent à celles de la dermatite lichénoïde psoriasiforme, bien que le virus du papillome puisse être détecté dans certains cas. Le chien du cas présent présentait quelques particularités dans les résultats histopathologiques et une implication du papillomavirus a été exclue par PCR. Comme observé dans un rapport précédent, il n'y avait pas de corrélation entre le taux sanguin de cyclosporine et la sévérité des altérations dermatologiques. L'arrêt de la cyclosporine a permis une guérison complète en 4 mois. Ce cas souligne l'importance d'une surveillance et d'un suivi réguliers des patients sous traitement immunosuppresseur. Les effets secondaires, même rares, doivent toujours être pris en compte dans ces cas.


Assuntos
Dermatite Atópica , Doenças do Cão , Papiloma , Cães , Feminino , Animais , Ciclosporina/efeitos adversos , Hiperplasia/induzido quimicamente , Hiperplasia/tratamento farmacológico , Hiperplasia/veterinária , Imunossupressores/efeitos adversos , Papiloma/patologia , Papiloma/veterinária , Dermatite Atópica/veterinária , Doença Crônica , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia
9.
J Am Anim Hosp Assoc ; 59(1): 45-50, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584313

RESUMO

The use of human serum albumin (HSA) is described in dogs receiving critical care. However, despite the high degree of homology, anaphylactic and delayed hypersensitivity reactions are reported. Delayed type III hypersensitivity reactions can lead to glomerulonephritis and acute kidney injury (AKI). Undiluted 20% HSA was administered to a 4.8 yr old intact male Labrador Retriever with severe hypoalbuminemia, following surgical management of septic peritonitis of gastrointestinal origin. Nineteen days after HSA administration, the dog developed peracute high magnitude renal proteinuria and AKI. Rapid immunosuppression, using a combination of prednisolone and mycophenolate mofetil, resulted in full resolution of AKI, hypoalbuminemia, and proteinuria. Addition of mycophenolate mofetil may have resulted in the first documented case of full renal recovery from hypersensitivity-induced AKI caused by HSA administration.


Assuntos
Injúria Renal Aguda , Doenças do Cão , Hipoalbuminemia , Humanos , Cães , Masculino , Animais , Ácido Micofenólico/efeitos adversos , Prednisolona/uso terapêutico , Albumina Sérica Humana , Hipoalbuminemia/veterinária , Doenças do Cão/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/veterinária , Proteinúria/veterinária , Imunossupressores/efeitos adversos
10.
Transpl Immunol ; 76: 101773, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36526105

RESUMO

BACKGROUND: Induction agents have proved to reduce the rate of acute rejection (AR) in kidney transplant recipients (KTRs) without improving long-term graft and patient survival (PS). OBJECTIVE: This study evaluates the utility of induction therapy in low immunological risk KTRs regardless of donor-to-recipient HLA matching. METHODS: We retrospectively reviewed the records of 218 patients undergoing kidney transplantation (KT). These patients were divided into two groups according to the usage of induction therapy: 82 did not receive any induction therapy (Group I), and 136 patients received either Anti-IL2 receptor antibodies or anti-thymocyte globulin (Group II). All patients had panel reactive antibody (PRA) < 20% and absence of donor-specific antibodies (DSA). The difference in outcomes were assessed at different intervals following KT. RESULTS: The rate of bacterial infections at one year (p-value = 0.032) and the frequency of CMV disease (p-value = 0.044) were significantly higher in Group II (with induction therapy). The duration of hospital stay, the rate and severity of acute rejection, the occurrence of delayed graft function, the rate and type of surgical complications at one year, and the graft function and survival at one and three years were similar between the two groups (p-value = NS). In addition, the financial burden is much less in Group I (without induction therapy), reducing the total cost of the transplant procedure. CONCLUSION: We conclude that induction therapy in low-immunological risk kidney transplant patients is not a must regardless of donor-to-recipient HLA matching. Therefore, induction therapy did not yield significant health results, but had negative financial consequences.


Assuntos
Imunossupressores , Transplante de Rim , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Quimioterapia de Indução , Rejeição de Enxerto , Anticorpos , Sobrevivência de Enxerto , Antígenos HLA , Transplantados
11.
Mult Scler Relat Disord ; 69: 104459, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36565573

RESUMO

BACKGROUND: Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT. METHODS: Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2-3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question. RESULTS: A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1-21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided. CONCLUSIONS: RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.


Assuntos
Cladribina , Esclerose Múltipla , Humanos , Cladribina/efeitos adversos , Prova Pericial , Linfócitos , Comprimidos/farmacologia , Recidiva , Imunossupressores/efeitos adversos
12.
Transplantation ; 107(1): 53-73, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508646

RESUMO

BACKGROUND: Chronic kidney disease (CKD) after lung transplantation is common and limits the survival of transplant recipients. The calcineurin inhibitors (CNI), cyclosporine A, and tacrolimus being the cornerstone of immunosuppression are key mediators of nephrotoxicity. The mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are increasingly used in combination with reduced CNI dosage after lung transplantation. METHODS: This systematic review examined the efficacy and safety of mTOR inhibitors after lung transplantation and explored their effect on kidney function. RESULTS: mTOR inhibitors are often introduced to preserve kidney function. Several clinical trials have demonstrated improved kidney function and efficacy of mTOR inhibitors. The potential for kidney function improvement and preservation increases with early initiation of mTOR inhibitors and low target levels for both mTOR inhibitors and CNI. No defined stage of CKD for mTOR inhibitor initiation exists, nor does severe CKD preclude the improvement of kidney function under mTOR inhibitors. Baseline proteinuria may negatively predict the preservation and improvement of kidney function. Discontinuation rates of mTOR inhibitors due to adverse effects increase with higher target levels. CONCLUSIONS: More evidence is needed to define the optimal immunosuppressive regimen incorporating mTOR inhibitors after lung transplantation. Not only the indication criteria for the introduction of mTOR inhibitors are needed, but also the best timing, target levels, and possibly discontinuation criteria must be defined more clearly. Current evidence supports the notion of nephroprotective potential under certain conditions.


Assuntos
Transplante de Rim , Transplante de Pulmão , Sirolimo/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Inibidores MTOR , Inibidores de Calcineurina/efeitos adversos , Imunossupressores/efeitos adversos , Serina-Treonina Quinases TOR , Transplante de Pulmão/efeitos adversos , Rim
13.
Sci Rep ; 12(1): 20926, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463264

RESUMO

Immunosuppressive treatment is a common cause of cytomegalovirus (CMV) reactivation. However, there is no consensus regarding the risk factors for CMV reactivation in rheumatic diseases. Therefore, this study aimed to elucidate the risk factors associated with CMV reactivation. We retrospectively collected the data of 472 patients with rheumatic diseases whose CMV pp65 antigen (C7-HRP) titer was measured. We divided the patients into those with and those without C7-HRP. We retrospectively collected data on age, sex, primary condition and organ involvement, and blood test results. We also investigated the use of immunosuppressants and the maximum and cumulative doses of prednisolone (PSL). We performed univariate and multivariate analyses to identify risk factors for CMV reactivation. Multivariate analysis showed that higher age (71.2 vs. 64.4 years, p = 0.0022), hypoalbuminemia (2.9 vs. 3.4 g/dL, p = 0.0104), higher creatinine level (1.2 vs. 0.9 mg/dL, p = 0.0026), cyclosporine use (8.2 vs. 3.6%, p = 0.0101), and higher maximum (552.4 vs. 243.3 mg, p < 0.0001) and cumulative (2785.9 vs. 1330.5 mg, p < 0.0001) doses of PSL were associated with CMV reactivation. Older age, hypoalbuminemia, higher creatinine level, cyclosporine use, and higher maximum and cumulative doses of PSL were significant risk factors for CMV reactivation in rheumatic diseases.


Assuntos
Ciclosporinas , Infecções por Citomegalovirus , Hipoalbuminemia , Doenças Reumáticas , Humanos , Estudos Retrospectivos , Citomegalovirus , Creatinina , Terapia de Imunossupressão , Doenças Reumáticas/tratamento farmacológico , Prednisolona/efeitos adversos , Imunossupressores/efeitos adversos , Fatores de Risco
14.
Diab Vasc Dis Res ; 19(6): 14791641221137352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36471497

RESUMO

BACKGROUND: Kidney transplantation is the treatment of choice for renal failure. Development of New-Onset Diabetes After Transplantation (NODAT) significantly increases kidney graft loss and mortality. This study aimed to evaluate the 10-years prevalence of NODAT in renal transplant patients. METHODS: In this cross-sectional study, medical records of non-diabetic patients undergoing kidney transplant in Shahid-Beheshti Hospital of Babol, between March 2009-2019 were retrospectively reviewed. RESULTS: Totally 284 patients with the mean age of 40.83 ± 12.94 years were included. New-Onset Diabetes After Transplantation was identified in 57 (20.1%) patients and 92.98% developed NODAT during the first month after transplantation. New-Onset Diabetes After Transplantation and non-NODAT patients were 43.8% and 34.38% female. Graft rejection occurred in 18 (31%) of NODAT and 78 (34%) of non-NODAT patients (p = .69). Patients with NODAT were about 10 years older (47.88 ± 11.06 vs 38.96 ± 13.12 years; p = .002). The pre-transplant Fasting Blood Sugar (FBS) was higher in the NODAT group (93.78 ± 13.78 vs 87.07 ± 11.56, p = .001) and post-transplantation cytomegalovirus (CMV) infection was higher in NODAT group (56% vs 40%, p = .021). New-Onset Diabetes After Transplantation patients had significantly higher BMI (27.16 ± 5.39 vs 23.94 ± 4.71, p < .001). CONCLUSION: New-Onset Diabetes After Transplantation is more prevalent in subjects with older age, higher BMI, post-transplant CMV infection, and higher pre-transplant FBS but gender, pre-transplant CMV infection, type of dialysis and smoking were not associated with it. So, these patients should be followed-up more diligently.


Assuntos
Infecções por Citomegalovirus , Diabetes Mellitus , Transplante de Rim , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Transplante de Rim/efeitos adversos , Incidência , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Estudos Transversais , Fatores de Risco , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/complicações , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia
15.
Iran J Kidney Dis ; 16(6): 330-336, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36454029

RESUMO

Increased risk of graft rejection could be the consequence of COVID-19 in kidney transplant recipients (KTRs). We report two cases of kidney transplant (KT) with stable graft function who experienced antibody-mediated rejection (ABMR) following recovery from COVID-19. It seems that reduced immunosuppression during the acute illness, is the main explanation for post-COVID-19 ABMR. However, the inflammatory state associated with COVID-19, as well as direct cytopathic effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can predispose the kidney allograft to rejection. There is no definite guideline for the modification of immunosuppressives during COVID-19 in kidney transplant recipients. However, re-institution of full-dose immunosuppressives soon after recovery from COVID-19 and frequent outpatient follow-up visits are recommended.  DOI: 10.52547/ijkd.7176.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Anticorpos , Rim , Imunossupressores/efeitos adversos , Aloenxertos
16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(6): 1112-1116, 2022 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-36533341

RESUMO

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.


Assuntos
Imunossupressores , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Ciclofosfamida/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Administração Intravenosa , Alopecia/induzido quimicamente , Alopecia/tratamento farmacológico
17.
Trials ; 23(1): 1012, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36514163

RESUMO

BACKGROUND: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. METHODS: CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. DISCUSSION: The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases. TRIAL REGISTRATION: EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016.


Assuntos
Doença Hepática Terminal , Hepatite Autoimune , Adulto , Humanos , Ácido Micofenólico/efeitos adversos , Azatioprina/efeitos adversos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Qualidade de Vida , Imunossupressores/efeitos adversos , Resultado do Tratamento , Índice de Gravidade de Doença , Prednisolona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
19.
BMJ Case Rep ; 15(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36524258

RESUMO

We report a case of a patient presenting with subacute neurological symptoms 10 years postkidney transplant. Cognitive deficits included acalculia and left upper limb dysesthesia, progressing to hemiplegic upper motor neuron weakness. Investigations included an MRI with multiple FLAIR hyperintensities, while a lumbar puncture was sterile with negative flow cytometry. Ultimately, PCR testing for John Cunningham virus was positive on cerebrospinal fluid. The diagnosis of progressive multifocal leukoencephalopathy (PML) was confirmed on the basis of the above.Initially, the patient was managed with withdrawal of immunosuppressants and close observation. Mirtazapine was commenced based on case reports of successful use in non-transplant patients; the patient's recovery was temporally related to withdrawal of immunosuppression and increasing mirtazapine dosage. The patient is currently maintained on prednisolone and mirtazapine with stable graft function and improved mobility and cognitive function.


Assuntos
Reconstituição Imune , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Humanos , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Mirtazapina , Imunossupressores/efeitos adversos
20.
BMC Med Inform Decis Mak ; 22(1): 336, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539772

RESUMO

BACKGROUND: Given its narrow treatment window, high toxicity, adverse effects, and individual differences in its use, we collected and sorted data on tacrolimus use by real patients with kidney diseases. We then used machine learning technology to predict tacrolimus blood concentration in order to provide a basis for tacrolimus dose adjustment and ensure patient safety. METHODS: This study involved 913 hospitalized patients with nephrotic syndrome and membranous nephropathy treated with tacrolimus. We evaluated data related to patient demographics, laboratory tests, and combined medication. After data cleaning and feature engineering, six machine learning models were constructed, and the predictive performance of each model was evaluated via external verification. RESULTS: The XGBoost model outperformed other investigated models, with a prediction accuracy of 73.33%, F-beta of 91.24%, and AUC of 0.5531. CONCLUSIONS: Through this exploratory study, we could determine the ability of machine learning to predict TAC blood concentration. Although the results prove the predictive potential of machine learning to some extent, in-depth research is still needed to resolve the XGBoost model's bias towards positive class and thereby facilitate its use in real-world settings.


Assuntos
Glomerulonefrite Membranosa , Síndrome Nefrótica , Humanos , Tacrolimo/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Imunossupressores/efeitos adversos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Resultado do Tratamento , Quimioterapia Combinada , Tecnologia
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