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1.
Adv Rheumatol ; 64(1): 38, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720354

RESUMO

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.


Assuntos
Antimaláricos , Azatioprina , Glucocorticoides , Hidroxicloroquina , Imunossupressores , Lúpus Eritematoso Sistêmico , Metotrexato , Prednisolona , Padrão de Cuidado , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Feminino , Imunossupressores/uso terapêutico , Hidroxicloroquina/uso terapêutico , Masculino , Glucocorticoides/uso terapêutico , Adulto , Azatioprina/uso terapêutico , Prednisolona/uso terapêutico , Metotrexato/uso terapêutico , Antimaláricos/uso terapêutico , Estudos de Coortes , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Leflunomida/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Modelos Logísticos , Pontuação de Propensão , Índice de Gravidade de Doença , Tacrolimo/uso terapêutico , Exacerbação dos Sintomas , Resultado do Tratamento , Antirreumáticos/uso terapêutico
2.
Pharmacogenomics J ; 24(3): 15, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769303

RESUMO

Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93-1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99-1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.


Assuntos
Taxa de Filtração Glomerular , Rejeição de Enxerto , IMP Desidrogenase , Imunossupressores , Transplante de Rim , Ácido Micofenólico , Polimorfismo de Nucleotídeo Único , Humanos , Transplante de Rim/efeitos adversos , IMP Desidrogenase/genética , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Adulto , Rejeição de Enxerto/genética , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Polimorfismo de Nucleotídeo Único/genética , Idoso , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/efeitos adversos
3.
BMJ Case Rep ; 17(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749521

RESUMO

A woman in her 70s presented with anasarca and exertional dyspnoea. Investigation showed severe hypoalbuminaemia with no urinary or gastrointestinal protein losses. CT thorax reported lung consolidations, and transbronchial lung biopsy demonstrated organising pneumonia. Autoimmune myositis serology was positive for anti-Jo-1, anti-Ro-52, and anti-PM/Scl-100 antibodies. She was diagnosed with anti-synthetase syndrome with organising pneumonia. She was treated with oral prednisolone and oral mycophenolate mofetil with a good clinical response.


Assuntos
Edema , Miosite , Humanos , Feminino , Miosite/tratamento farmacológico , Miosite/diagnóstico , Miosite/complicações , Miosite/imunologia , Idoso , Edema/tratamento farmacológico , Edema/etiologia , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Ácido Micofenólico/uso terapêutico , Tomografia Computadorizada por Raios X , Pneumonia/tratamento farmacológico , Pneumonia/diagnóstico , Dispneia/etiologia
4.
J Pak Med Assoc ; 74(5): 868-873, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783432

RESUMO

Objectives: To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. METHODS: The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26. RESULTS: Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05). CONCLUSIONS: Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.


Assuntos
Ciclofosfamida , Imunossupressores , Nefrite Lúpica , Ácido Micofenólico , Centros de Atenção Terciária , Humanos , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Adulto , Paquistão , Masculino , Imunossupressores/uso terapêutico , Adulto Jovem , Resultado do Tratamento , Estudos de Coortes , Tacrolimo/uso terapêutico , Quimioterapia de Indução/métodos , Indução de Remissão/métodos
5.
Mar Drugs ; 22(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38786581

RESUMO

Influenza A virus (IAV) can cause infection and illness in a wide range of animals, including humans, poultry, and swine, and cause annual epidemics, resulting in thousands of deaths and millions of hospitalizations all over the world. Thus, there is an urgent need to develop novel anti-IAV drugs with high efficiency and low toxicity. In this study, the anti-IAV activity of a marine-derived compound mycophenolic acid methyl ester (MAE) was intensively investigated both in vitro and in vivo. The results showed that MAE inhibited the replication of different influenza A virus strains in vitro with low cytotoxicity. MAE can mainly block some steps of IAV infection post adsorption. MAE may also inhibit viral replication through activating the cellular Akt-mTOR-S6K pathway. Importantly, oral treatment of MAE can significantly ameliorate pneumonia symptoms and reduce pulmonary viral titers, as well as improving the survival rate of mice, and this was superior to the effect of oseltamivir. In summary, the marine compound MAE possesses anti-IAV effects both in vitro and in vivo, which merits further studies for its development into a novel anti-IAV drug in the future.


Assuntos
Antivirais , Vírus da Influenza A , Ácido Micofenólico , Infecções por Orthomyxoviridae , Replicação Viral , Animais , Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Ácido Micofenólico/farmacologia , Camundongos , Replicação Viral/efeitos dos fármacos , Humanos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Camundongos Endogâmicos BALB C , Cães , Feminino , Células Madin Darby de Rim Canino , Células A549 , Organismos Aquáticos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia
6.
Arthritis Res Ther ; 26(1): 79, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570792

RESUMO

INTRODUCTION: Idiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM. METHODS: Patients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period. RESULTS: Among the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed. CONCLUSION: Our data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.


Assuntos
Ácido Micofenólico , Miosite , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Rituximab/efeitos adversos , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Miosite/tratamento farmacológico , Miosite/induzido quimicamente
7.
Swiss Med Wkly ; 154: 3630, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38579324

RESUMO

OBJECTIVES: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. METHODS: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. RESULTS: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. CONCLUSION: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.


Assuntos
Antirreumáticos , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Suíça , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Fibrose , Antirreumáticos/uso terapêutico
8.
Transpl Int ; 37: 12720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655204

RESUMO

Infectious complications, including widespread human cytomegalovirus (CMV) disease, frequently occur after hematopoietic stem cell and solid organ transplantation due to immunosuppressive treatment causing impairment of T-cell immunity. Therefore, in-depth analysis of the impact of immunosuppressants on antiviral T cells is needed. We analyzed the impact of mTOR inhibitors sirolimus (SIR/S) and everolimus (EVR/E), calcineurin inhibitor tacrolimus (TAC/T), purine synthesis inhibitor mycophenolic acid (MPA/M), glucocorticoid prednisolone (PRE/P) and common double (T+S/E/M/P) and triple (T+S/E/M+P) combinations on antiviral T-cell functionality. T-cell activation and effector molecule production upon antigenic stimulation was impaired in presence of T+P and triple combinations. SIR, EVR and MPA exclusively inhibited T-cell proliferation, TAC inhibited activation and cytokine production and PRE inhibited various aspects of T-cell functionality including cytotoxicity. This was reflected in an in vitro infection model, where elimination of CMV-infected human fibroblasts by CMV-specific T cells was reduced in presence of PRE and all triple combinations. CMV-specific memory T cells were inhibited by TAC and PRE, which was also reflected with double (T+P) and triple combinations. EBV- and SARS-CoV-2-specific T cells were similarly affected. These results highlight the need to optimize immune monitoring to identify patients who may benefit from individually tailored immunosuppression.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Everolimo , Imunossupressores , Ácido Micofenólico , Sirolimo , Linfócitos T , Tacrolimo , Humanos , Infecções por Citomegalovirus/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Citomegalovirus/imunologia , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Prednisolona/uso terapêutico , Transplante de Órgãos , Proliferação de Células/efeitos dos fármacos
10.
Medicine (Baltimore) ; 103(14): e37821, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579022

RESUMO

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.


Assuntos
Hipertensão , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Feminino , Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/diagnóstico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Resultado do Tratamento , Ciclofosfamida/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Ácido Micofenólico/uso terapêutico , Hipertensão/complicações , Resposta Patológica Completa , Indução de Remissão
11.
BMC Pediatr ; 24(1): 291, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689221

RESUMO

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.


Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Glomerulonefrite por IGA , Humanos , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/genética , Masculino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Criança , Imunoglobulinas Intravenosas/uso terapêutico , Glucocorticoides/uso terapêutico , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico
12.
J Med Case Rep ; 18(1): 229, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689344

RESUMO

BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive drug that is frequently prescribed to patients with rheumatological diseases. MMF's side effects include abdominal discomfort, nausea, vomiting, and other gastro-intestinal side effects, which typically appear in the first few months of treatment. However, late-onset diarrhea does not rule out the presence of MMF-induced colitis, which can be misdiagnosed since it is linked to a broad range of histopathological characteristics, including alterations that resemble inflammatory bowel disease, graft-versus-host disease, and ischemia. The differences in treatment response may be explained by the complexity of the histopathologic characteristics. CASE PRESENTATION: Here we present a case of a 29-year-old Arabian female with lupus nephritis who started on MMF as induction therapy. In two months, the patient was presented to the Emergency Department with diarrhea and manifestations of severe dehydration. Infectious diseases and adverse drug events were suspected, so the patient was admitted for further workup, and MMF was stopped. The patient was diagnosed with MMF-induced colitis based on colonoscopy and histological findings. Fourteen days after stopping MMF, she was within her baseline. CONCLUSION: The purpose of this paper is to report a case of early-onset MMF-induced colitis in a patient with lupus nephritis who had started MMF as induction therapy. A review of the available literature on this uncommon immunosuppressive effect is also presented.


Assuntos
Colite , Imunossupressores , Nefrite Lúpica , Ácido Micofenólico , Adulto , Feminino , Humanos , Colite/induzido quimicamente , Colonoscopia , Diarreia/induzido quimicamente , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico
13.
Neuromuscul Disord ; 38: 51-57, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38626662

RESUMO

Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.


Assuntos
Azatioprina , Imunossupressores , Metotrexato , Miastenia Gravis , Ácido Micofenólico , Humanos , Miastenia Gravis/tratamento farmacológico , Metotrexato/uso terapêutico , Metotrexato/efeitos adversos , Feminino , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Reino Unido
14.
Tunis Med ; 102(1): 38-43, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38545728

RESUMO

INTRODUCTION: Pediatric end-stage renal disease is a rare but severe condition that causes numerous complications and impairs the quality of life of children. Kidney transplantation is the therapy of choice in pediatric end-stage renal disease. AIM: Our study aimed to identify the predictive factors of renal graft failure after kidney transplantation in Tunisian children and young adults. METHODS: We conducted a retrospective bicentric study of children and young adults (age≤20 years) who had undergone renal transplantation between 1989 and 2019 in Tunisia. We analyzed long-term survival rates and complications after pediatric kidney transplantation and searched for predictive parameters for graft dysfunction. We used a univariate and a multivariate analysis to identify predictive factors of graft survival. RESULTS: A total of 112 patients underwent 115 kidney transplantations. Graft failure occurred in 30% of the cases. The overall 1-, 3-, 5- and 10-year graft survival rates were 92%, 89.1%, 85.9% and 74.5% respectively. The following parameters strongly influenced graft survival: immunosuppressive regimen including an association other than Mycophenolate mofetil- tacrolimus and corticosteroids (p=0.002), year of transplant (p<0.0001 for 1987-2000), deceased donor (p = 0.039), underlying etiology of end-stage renal disease (p=0.045), occurrence of acute or chronic rejection (p<0.001), a urine protein greater than 0.3 g/l per day (p=0.002), post-transplant urologic complications (p=0.002), five-year creatinine level>1.28 mg/dl (p<0.001). The overall 1-, 3-, 5- and 10-year patients survival rates were 97%, 95%, 90.2% and 84.4% respectively. CONCLUSIONS: Our study identified several predictive factors of graft failure in Tunisian children and young adults undergoing renal transplantation.


Assuntos
Nefropatias , Falência Renal Crônica , Humanos , Criança , Adulto Jovem , Adulto , Estudos Retrospectivos , Qualidade de Vida , Imunossupressores/uso terapêutico , Tacrolimo , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Ácido Micofenólico
15.
Expert Opin Drug Saf ; 23(4): 513-525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38533933

RESUMO

OBJECTIVE: The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned. METHODS: The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs. RESULTS: Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia. CONCLUSION: The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies. EXPERT OPINION: The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.


Assuntos
Transplante de Rim , Tacrolimo , Humanos , Tacrolimo/efeitos adversos , Farmacovigilância , Imunossupressores/efeitos adversos , Ciclosporina/efeitos adversos , Ácido Micofenólico , Metotrexato , Mineração de Dados , Rejeição de Enxerto
16.
J Dtsch Dermatol Ges ; 22(4): 605-620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426689

RESUMO

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.


Assuntos
Fármacos Dermatológicos , Esclerodermia Localizada , Humanos , Metotrexato/uso terapêutico , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/terapia , Pele , Fármacos Dermatológicos/uso terapêutico , Ácido Micofenólico/uso terapêutico
17.
Epidemiol Health ; 46: e2024012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476014

RESUMO

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.


Assuntos
Lúpus Eritematoso Sistêmico , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/tratamento farmacológico , Resultado da Gravidez , Imunossupressores/uso terapêutico , Ciclofosfamida/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Ácido Micofenólico/uso terapêutico , República da Coreia
18.
Artigo em Russo | MEDLINE | ID: mdl-38465811

RESUMO

OBJECTIVE: Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory demyelinating polyneuropathy (CIDP). MATERIAL AND METHODS: Patients (n=30) were observed in a separate structural unit of the Russian Children's Clinical Hospital of the Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of the Russian Federation in the period from 2006 to 2023. The examination was carried out in accordance with the recommendations of the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society on the Management of CIDP (2021). All patients received immunotherapy, including intravenous immunoglobulin (IVIG) (n=1), IVIG and glucocorticosteroids (GCS) (n=17, 56.7%), IVIG+GCS+plasmapheresis (n=12, 40.0%). Alternative therapy included cyclophosphamide (n=1), cyclophosphamide followed by mycophenolate mofetil (n=1), rituximab (n=2, 6.6%), azathioprine (n=3), mycophenolate mofetil (n=2, 6.6%). RESULTS: In all patients, there was a significant difference between scores on the MRCss and INCAT functional scales before and after treatment. At the moment, 11/30 (36.6%) patients are in clinical remission and are not receiving pathogenetic therapy. The median duration of remission is 48 months (30-84). The longest remission (84 months) was observed in a patient with the onset of CIDP at the age of 1 year 7 months. CONCLUSION: Early diagnosis of CIDP is important, since the disease is potentially curable; early administration of pathogenetic therapy provides a long-term favorable prognosis.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Criança , Lactente , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/efeitos adversos , Ácido Micofenólico/uso terapêutico , Nervos Periféricos , Ciclofosfamida/uso terapêutico
19.
Am J Case Rep ; 25: e941214, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442088

RESUMO

BACKGROUND The incidence of renal cell carcinoma (RCC) in transplanted kidneys is reported to be about 0.2%, which makes this case exceedingly rare. Risk factors include older age of the donors, smoking, obesity, and hypertension. Higher incidences of allograft RCC have been seen in patients who received a kidney from a deceased donor rather than from a living donor. CASE REPORT A 71-year-old woman with end-stage renal disease underwent deceased donor kidney transplantation (DDKT) 1 year before presentation. The immune-suppressive regimen was Envarsus, Myfortic, and prednisone. Allograft functioned with a baseline creatinine of 1.4-1.5 mg/dL. The patient presented due to recurring UTIs, which prompted the ultrasound that showed a mass on the allograft. Abdominal MRI demonstrated a 3.5-cm mass in the upper pole. Biopsy showed clear-cell RCC, Fuhrman nuclear grade 3. The patient underwent a partial nephrectomy. Following the nephrectomy, baseline serum creatinine was 1.7-2 mg/dL. The patient was discharged with immunosuppressive therapy consisting of Myfortic, prednisone, and Rapamune after diagnosis. CONCLUSIONS There are no standard treatment guidelines or optimal immune therapy for the management of allograft RCC in renal transplant recipients. Options include radical nephrectomy, nephron-sparing surgery (NSS), radiofrequency ablation (RFA), and active surveillance. According to a systematic review, the recurrence of cancer after partial nephrectomy was 3.6% after 3.1 years, which was similar to non-transplanted kidneys. There is not enough evidence to support screening for RCC in patients with transplanted kidneys, but constitutional symptoms like recurrent UTIs should prompt further investigation for potential malignancies in these patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Idoso , Feminino , Humanos , Carcinoma de Células Renais/cirurgia , Creatinina , Neoplasias Renais/cirurgia , Ácido Micofenólico , Prednisona
20.
Int J Biol Macromol ; 265(Pt 2): 131023, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513897

RESUMO

The interactions between bovine serum albumin (BSA) and mycophenolic acid (MPA) were investigated in silico through molecular docking and in vitro, using fluorescence spectroscopy. Dynamic light scattering and scanning electron microscopy were used to figure out the structure of MPA-Complex (MPA-C). The binding affinity between MPA and BSA was determined, yielding a Kd value of (12.0 ± 0.7) µM, and establishing a distance of 17 Å between the BSA and MPA molecules. The presence of MPA prompted protein aggregation, leading to the formation of MPA-C. The cytotoxicity of MPA-C and its ability to fight Junín virus (JUNV) were tested in A549 and Vero cell lines. It was found that treating infected cells with MPA-C decreased the JUNV yield and was more effective than free MPA in both cell line models for prolonged time treatments. Our results represent the first report of the antiviral activity of this type of BSA-MPA complex against JUNV, as assessed in cell culture model systems. MPA-C shows promise as a candidate for drug formulation against human pathogenic arenaviruses.


Assuntos
Vírus Junin , Soroalbumina Bovina , Humanos , Ácido Micofenólico , Simulação de Acoplamento Molecular , Replicação Viral , Antivirais/farmacologia
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