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1.
Skin Res Technol ; 30(3): e13642, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454597

RESUMO

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


Assuntos
Azetidinas , Hipopigmentação , Purinas , Pirazóis , Sulfonamidas , Talidomida/análogos & derivados , Vitiligo , Humanos , Metotrexato/uso terapêutico , Azatioprina/uso terapêutico , Vitiligo/tratamento farmacológico , Vitiligo/patologia , Ácido Micofenólico/uso terapêutico , Minociclina/uso terapêutico , Alefacept/uso terapêutico , Ciclosporina/uso terapêutico , Corticosteroides , Sinvastatina/uso terapêutico , Zinco/uso terapêutico
2.
J Infect ; 88(3): 106133, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432583

RESUMO

OBJECTIVES: To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. METHODS: In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort. RESULTS: Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040). CONCLUSIONS: MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.


Assuntos
Influenza Humana , Transplante de Rim , Tétano , Humanos , Pessoa de Meia-Idade , Idoso , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Influenza Humana/tratamento farmacológico , Formação de Anticorpos , Vacinas contra COVID-19 , Tétano/prevenção & controle , Tétano/tratamento farmacológico
3.
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
4.
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
5.
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
6.
BMJ Open ; 14(3): e074662, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38471694

RESUMO

INTRODUCTION: Several studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis because of its strong immunosuppressive potency and low toxicity profile. Enteric-coated mycophenolate sodium (EC-MPS) was introduced to reduce gastrointestinal adverse reactions of MMF. This study will evaluate the efficacy and safety of EC-MPS combined with glucocorticoid in patients with active and non-life-threatening microscopic polyangiitis (MPA). METHODS AND ANALYSIS: This study is a multicentre, open-label, randomised controlled, non-inferiority trial. A total of 110 patients with active and non-life-threatening MPA from 11 hospitals in Shanxi Province of China will be recruited and randomised in a 1:1 ratio to receive either EC-MPS or CYC. All patients will receive the same glucocorticoid plan. We will compare oral EC-MPS (720-1440 mg/day) with intravenous pulsed CYC (7.5-15 mg/kg) administered for 3-6 months. All patients will be switched from their assigned treatment (EC-MPS or CYC) to oral azathioprine (2 mg/kg/day) after remission has been achieved, between 3 and 6 months. Azathioprine will be continued until the study ends at 18 months. The primary end point of efficacy is the remission rate at 6 months. Follow-up will continue for 18 months in order to detect an influence of induction regimen on subsequent relapse rates. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of the Second Hospital of Shanxi Medical University (2022YX-026). All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of this trial will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200063823.


Assuntos
Poliangiite Microscópica , Ácido Micofenólico , Humanos , Ácido Micofenólico/efeitos adversos , Azatioprina , Glucocorticoides , Imunossupressores/efeitos adversos , Ciclofosfamida , Indução de Remissão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
7.
Transplant Proc ; 56(2): 459-462, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368132

RESUMO

The onset of gastroduodenal ulcers is a frequent complication after transplantation, whereas cases of intestinal ulcers are sporadic and poorly described in the literature. A patient on immunosuppressive therapy with tacrolimus and mycophenolate mofetil after kidney transplant for immunoglobulin A-related glomerulonephritis developed symptoms compatible with Crohn disease 7 months after the transplant. The patient was hospitalized for abdominal pain, diarrhea, fever, and weight loss. Imaging and a colonoscopy showed signs of idiopathic inflammatory bowel disease (IBD) affecting the terminal ileum. Behcet's disease, post-transplant lymphoma, cytomegalovirus, Epstein-Barr virus, or mycobacteria infection were excluded. Mycophenolate mofetil was suspended, and steroid therapy was increased without clinical improvement. Eleven units of blood were required for severe anemia. A further colonoscopy revealed ulcerations involving the cecal fundus, ileocecal valve, and distal ileum with bowel stenosis and suspected ischemia. The patient, therefore, underwent an emergency laparoscopic ileocolic resection. The histologic examination did not reveal clear signs of IBD, ischemia, or viral infection of the ileum. The findings seemed indicative of iatrogenic damage from immunosuppressive therapy. The postoperative course was regular, and after 12 months, the patient was asymptomatic, on low-dose tacrolimus and prednisone therapy. During immunosuppressive therapy, the onset of isolated ileal ulcers, which can mimic IBD, may be a sporadic complication.


Assuntos
Doença de Crohn , Infecções por Vírus Epstein-Barr , Doenças Inflamatórias Intestinais , Transplante de Rim , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Herpesvirus Humano 4 , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Isquemia , Transplante de Rim/efeitos adversos , Ácido Micofenólico/efeitos adversos , Tacrolimo/efeitos adversos , Úlcera/induzido quimicamente , Úlcera/diagnóstico
8.
Lancet Rheumatol ; 6(3): e168-e177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301682

RESUMO

BACKGROUND: Mycophenolate mofetil is an immunosuppressant commonly used to treat systemic lupus erythematosus (SLE) and lupus nephritis. It is a known teratogen associated with significant toxicities, including an increased risk of infections and malignancies. Mycophenolate mofetil withdrawal is desirable once disease quiescence is reached, but the timing of when to do so and whether it provides a benefit has not been well-studied. We aimed to determine the effects of mycophenolate mofetil withdrawal on the risk of clinically significant disease reactivation in patients with quiescent SLE on long-term mycophenolate mofetil therapy. METHODS: This multicenter, open-label, randomised trial was conducted in 19 centres in the USA. Eligible patients were aged between 18 and 70 years old, met the American College of Rheumatology (ACR) 1997 SLE criteria, and had a clinical SLEDAI score of less than 4 at screening. Mycophenolate mofetil therapy was required to be stable or decreasing for 2 years or more if initiated for renal indications, or for 1 year or more for non-renal indications. Participants were randomly allocated in a 1:1 ratio to a withdrawal group, who tapered off mycophenolate mofetil over 12 weeks, or a maintenance group who maintained their baseline dose (1-3g per day) for 60 weeks. Adaptive random allocation ensured groups were balanced for study site, renal versus non-renal disease, and baseline mycophenolate mofetil dose (≥2 g per day vs <2 g per day). Clinically significant disease reactivation by week 60 following random allocation, requiring increased doses or new immunosuppressive therapy was the primary endpoint, in the modified intention-to-treat population (all randomly allocated participants who began study-provided mycophenolate mofetil). Non-inferiority was evaluated using an estimation-based approach. The trial was registered at ClinicalTrials.gov (NCT01946880) and is completed. FINDINGS: Between Nov 6, 2013, and April 27, 2018, 123 participants were screened, of whom 102 were randomly allocated to the maintenance group (n=50) or the withdrawal group (n=52). Of the 100 participants included in the modified intention-to-treat analysis (49 maintenance, 51 withdrawal), 84 (84%) were women, 16 (16%) were men, 40 (40%) were White, 41 (41%) were Black, and 76 (76%) had a history of lupus nephritis. The average age was 42 (SD 12·7). By week 60, nine (18%) of 51 participants in the withdrawal group had clinically significant disease reactivation, compared to five (10%) of 49 participants in the maintenance group. The risk of clinically significant disease reactivation was 11% (95% CI 5-24) in the maintenance group and 18% (10-32) in the withdrawal group. The estimated increase in the risk of clinically significant disease reactivation with mycophenolate mofetil withdrawal was 7% (one-sided upper 85% confidence limit 15%). Similar rates of adverse events were observed in the maintenance group (45 [90%] of 50 participants) and the withdrawal group (46 [88%] of 52 participants). Infections were more frequent in the mycophenolate mofetil maintenance group (32 [64%]) compared with the withdrawal group (24 [46%]). INTERPRETATIONS: Mycophenolate mofetil withdrawal is not significantly inferior to mycophenolate mofetil maintenance. Estimates for the rates of disease reactivation and increases in risk with withdrawal can assist clinicians in making informed decisions on withdrawing mycophenolate mofetil in patients with stable SLE. FUNDING: The National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Masculino , Humanos , Feminino , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Ácido Micofenólico/efeitos adversos , Nefrite Lúpica/tratamento farmacológico , Resultado do Tratamento , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico
9.
J Med Case Rep ; 18(1): 93, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38350929

RESUMO

BACKGROUND: Scleredema adultorum of Buschke is a rare disease characterized by firm and non-pitting edema of the skin. The condition is rare with unknown etiology. Diagnosis is made on the basis of clinical findings and skin biopsy. CASE PRESENTATION: Here, we describe a 14-year-old Iranian girl presenting with non-pitting edema and woody thickening of the skin that progressed within a month. She was evaluated for possible underlying malignancy or connective tissue disorders, which were excluded by multiple laboratory workups. She underwent a skin biopsy which confirmed the diagnosis of scleredema, and she was successfully treated with intravenous immunoglobulin and mycophenolate mofetil. CONCLUSION: While scleredema adultorum of Buschke is a rare disease with no definite treatment, our effort through this report was to highlight the possible benefits of treatment by intravenous immunoglobulin and mycophenolate mofetil.


Assuntos
Escleredema do Adulto , Feminino , Humanos , Adolescente , Escleredema do Adulto/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Ácido Micofenólico/uso terapêutico , Irã (Geográfico) , Doenças Raras , Edema
10.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38397035

RESUMO

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug-drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.


Assuntos
Fibrose Cística , Transplante de Pulmão , Humanos , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/farmacologia , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Antibacterianos/uso terapêutico , Imunossupressores/efeitos adversos , Inibidores Enzimáticos
11.
Lancet Neurol ; 23(3): 267-276, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38365379

RESUMO

BACKGROUND: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. METHODS: We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). FINDINGS: Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. INTERPRETATION: More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. FUNDING: Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.


Assuntos
Azatioprina , Miastenia Gravis , Ácido Micofenólico , Adolescente , Adulto , Humanos , Azatioprina/efeitos adversos , Imunossupressores/efeitos adversos , Miastenia Gravis/tratamento farmacológico , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Qualidade de Vida
12.
Medicine (Baltimore) ; 103(6): e36999, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335395

RESUMO

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.


Assuntos
Hepatopatias , Lúpus Eritematoso Sistêmico , Humanos , Pessoa de Meia-Idade , Feminino , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Hemissuccinato de Metilprednisolona/uso terapêutico , Bilirrubina
13.
BMJ Open Respir Res ; 11(1)2024 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413120

RESUMO

OBJECTIVES: Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD. DESIGN: Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded. DATA SYNTHESIS: The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design. RESULTS: A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I2=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence. CONCLUSIONS: There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD. PROSPERO REGISTRATION NUMBER: CRD42023423223.


Assuntos
Azatioprina , Doenças Pulmonares Intersticiais , Humanos , Azatioprina/uso terapêutico , Azatioprina/farmacologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/farmacologia , Inibidores Enzimáticos/uso terapêutico , Estudos Observacionais como Assunto
14.
J Neuroimmunol ; 388: 578294, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306927

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Feminino , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Ácido Micofenólico/uso terapêutico , Leucócitos Mononucleares , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/diagnóstico
15.
Curr Opin Nephrol Hypertens ; 33(3): 311-317, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411173

RESUMO

PURPOSE OF REVIEW: As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease. RECENT FINDINGS: The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use. SUMMARY: Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.


Assuntos
Glomerulonefrite por IGA , Insuficiência Renal Crônica , Humanos , Glomerulonefrite por IGA/tratamento farmacológico , Padrão de Cuidado , Insuficiência Renal Crônica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Glucocorticoides/uso terapêutico , Proteinúria/tratamento farmacológico
16.
Transplant Proc ; 56(2): 297-305, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395659

RESUMO

BACKGROUND: To describe and establish the efficacy and safety of Mycophenolate Mofetil (Micoflavin) in patients with de novo renal transplantation during one-year post-transplant follow-up. As secondary objectives, the behavior of mycophenolic acid (MPA) C0 levels in this population, the relationship between MPA levels and renal function of the grafts, the incidence of acute rejection, and the incidence of adverse effects were evaluated. METHODS: A prospective cohort study was conducted on patients who received a first kidney transplant from a deceased donor between March 1, 2021, and February 28, 2022, at the Alma Mater of Antioquia Hospital of the Antioquia's University, in Medellín, Colombia. MPA C0 levels were taken from the patients on days 15, 30, 90, 180, and 360 after the kidney transplantation. RESULTS: Patients presented MPA therapeutic levels in the study. The average of the MPA levels in the population was 2.5 µg/mL, with an IQR of 2.13 to 3.32. There were 5 acute rejections (27%), but none of the patients with acute rejection presented subtherapeutic levels of mycophenolate. No significant relationship was observed between mycophenolic acid levels and rejection (P = .255). The patients who completed the study had no gastrointestinal intolerance to mycophenolate, cytomegalovirus infections, or significant hematological complications. CONCLUSIONS: MMF (Micoflavin) maintained mycophenolic acid levels C0 within the therapeutic range, was well tolerated and without the presence of significant adverse events, and maintained stable renal function throughout the follow-up period in the population studied.


Assuntos
Transplante de Rim , Ácido Micofenólico , Humanos , Ácido Micofenólico/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Transplantados , Estudos Prospectivos , Colômbia , Imunossupressores/efeitos adversos , Inibidores Enzimáticos , Rejeição de Enxerto/epidemiologia
17.
J Pediatr Gastroenterol Nutr ; 78(2): 328-338, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38374561

RESUMO

OBJECTIVES: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes. METHODS: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries. RESULTS: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only. CONCLUSIONS: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices.


Assuntos
Transplante de Rim , Transplante de Fígado , Criança , Humanos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico
18.
Exp Clin Transplant ; 22(Suppl 1): 73-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38385377

RESUMO

OBJECTIVES: Respiratory tract infections are life-threatening infections in solid-organ transplant recipients that pose risk to the graft and to the patient. This study was undertaken to examine the clinical and microbiological spectrum of pneumonia in renal transplant recipients. MATERIALS AND METHODS: Of 400 consecutive renal transplant recipients, 87 recipients (21.8%) were hospitalized between November 2014 and October 2016 with pneumonia. We examined demographic profiles and clinical investigations. RESULTS: The median age of patients was 38 years (range, 19-72 y). The mean time of presentation after renal transplant was 18 months (range, 1-174 mo). Most patients (80.5%) were on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids; 34% of patients had an induction agent. Chronic hepatitis C and hepatitis B infections were found in 12.6% and 2.2% of patients, respectively, and new-onset diabetes in 19.5% of patients. Fever (88%), cough (87%), shortness of breath (68%), and hypotension (33%) were common presenting symptoms. Diarrhea was the most frequent accompanying symptom, found in 9.2% of patients. Cytopenia and graft dysfunction were present in 38.7% and 80.4% of patients. Among infections, fungal infections were the most frequent (30%) followed by mixed infections (20.7%), tuberculosis (12.6%), bacterial (12.6%), and viral (3.5%) infections. Etiology could not be found in 27.6% patients. Mortality rate was 24.1%, with the highest rates for fungal infections (44%), followed by bacterial (25%) and mixed infections (18%). Presence of hypoxia and hypotension at presentation was associated with increased risk of death, whereas use of induction agents, new-onset diabetes posttransplant, diabetes mellitus, and acute kidney injury were not correlated with death or increased duration of hospital stay. CONCLUSIONS: Pneumonia carries high risk of mortality in renal transplant recipients. Fungal and bacterial infections carry high risk of mortality. Despite invasive investigations, a substantial number of patients had unidentified etiology.


Assuntos
Coinfecção , Diabetes Mellitus , Hipotensão , Transplante de Rim , Micoses , Pneumonia , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Coinfecção/induzido quimicamente , Coinfecção/complicações , Ácido Micofenólico/efeitos adversos , Diabetes Mellitus/etiologia , Pneumonia/induzido quimicamente , Hipotensão/etiologia , Transplantados , Rejeição de Enxerto
19.
J Microbiol Biotechnol ; 34(2): 249-261, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419324

RESUMO

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.


Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Lanosterol/análogos & derivados , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Ácido Micofenólico/farmacologia , Antineoplásicos/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carboxilesterase
20.
Mult Scler ; 30(3): 357-368, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38314479

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. OBJECTIVE: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). METHODS: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. RESULTS: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33). CONCLUSION: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.


Assuntos
Autoanticorpos , Imunoglobulinas Intravenosas , Humanos , Criança , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos , Prednisona , Recidiva Local de Neoplasia , Ácido Micofenólico , Imunoterapia , Recidiva
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