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1.
BMJ ; 368: m421, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188597

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Imunossupressores/uso terapêutico , Azatioprina , Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Rituximab/uso terapêutico
2.
Lancet Haematol ; 7(2): e100-e111, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31958417

RESUMO

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60­7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9­23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9­25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2­29·2) versus 31·3% (21·9­40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5­35·1) in the anti-thymocyte globulin group and 41·3% (31·3­51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6­78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8­62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35­0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.


Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Imunossupressores/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Idoso , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Linfócitos T/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
3.
Paediatr Drugs ; 21(6): 461-467, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31667717

RESUMO

Juvenile localized scleroderma (jLS) is an orphan disease that can lead to cosmetic disfiguration and orthopedic problems. Two recent publications review the current recommendations regarding diagnosis, assessment, follow up and treatment of pediatric localized scleroderma cases, both of which suggest the Localized Scleroderma Cutaneous Assessment Tool as an important instrument to assess activity and damage. This review focuses on the systemic treatment of jLS. Systemic treatment includes synthetic and biologic disease-modifying antirheumatic drugs. Systemic therapy is indicated if the lesion crosses any joint, or leads to potential cosmetic disfiguration or orthopedic problems. The only controlled trial of systemic treatment has shown the efficacy of methotrexate, which is the first choice of treatment. It appears superior to phototherapy according to a recently published meta-analysis. In case of methotrexate intolerance, mycophenolate mofetil is an option. In case of methotrexate nonresponse, addition of mycophenolate mofetil, tocilizumab or abatacept seems to be effective. Future treatment options derived and extrapolated from adult trials regarding treatment of skin involvement of systemic scleroderma or fibrosis are promising, as the final pathway in the skin seems to be similar in both diseases.


Assuntos
Esclerodermia Localizada/tratamento farmacológico , Antirreumáticos/uso terapêutico , Criança , Humanos , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Fototerapia
5.
Ann Hematol ; 98(11): 2579-2591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628517

RESUMO

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , /etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
7.
Muscle Nerve ; 60(6): 707-715, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31487038

RESUMO

INTRODUCTION: The Myasthenia Gravis Patient Registry (MGR) is a voluntary, patient-submitted database dedicated to improve understanding of care/burden of myasthenia gravis (MG). METHODS: In this study we present analyses of baseline records through July 2017 (n = 1140) containing data on the MG-Activities of Daily Living (MG-ADL) and the MG 15-item Quality of Life (MG-QOL15) instruments, two validated scales assessing quality of life in MG patients at sign-up into the MGR. RESULTS: Most registrants reported moderate to severe impairment of health-related quality of life, with a median MG-ADL score of 6 and a median MG-QOL15 score of 21. Seventy-one percent of the patients had received pyridostigmine. Corticosteroids, mycophenolate mofetil, and azathioprine were the most common immunomodulators/immunosuppressants, with 85% of participants having ever using one of these agents. Forty-seven registrants reported receiving intravenous immunoglobulin, and 30% received plasma exchange. Twelve percent reported other treatments, and 40% were unsure whether they received less common therapies. Forty percent had undergone thymectomy. DISCUSSION: The MGR data correlate well with other MG cohorts. Many MG patients remain negatively impacted despite treatment.


Assuntos
Atividades Cotidianas , Inibidores da Colinesterase/uso terapêutico , Imunossupressores/uso terapêutico , Miastenia Gravis/fisiopatologia , Miastenia Gravis/terapia , Qualidade de Vida , Corticosteroides/uso terapêutico , Adulto , Idoso , Azatioprina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Troca Plasmática/métodos , Brometo de Piridostigmina/uso terapêutico , Sistema de Registros
8.
BMJ Case Rep ; 12(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31519721

RESUMO

Antisynthetase syndrome is a rare autoimmune disease and represents a distinct entity within the idiopathic inflammatory myopathies. Its variable systemic manifestations are composed of myositis, interstitial lung disease, non-erosive arthritis, fever, Raynaud's phenomenon, hyperkeratotic skin changes and the presence of antibodies against aminoacyl-transfer-RNA-synthetases. Interstitial lung disease is the major determinant of morbidity and mortality. The role of lung biopsy remains controversial but it might be considered on an individual basis and may provide information regarding prognosis and treatment response. An integrated clinical, radiological and pathological approach to interstitial lung disease has to be emphasised. Due to the rarity of the disease, no standardised treatment guidelines for antisynthetase syndrome exist. We discuss a patient with anti-Jo1-autoantibody antisynthetase syndrome with proximal myositis and severe, rapid onset, interstitial lung disease with a histopathological pattern of organising pneumonia on surgical lung biopsy and good response to early combined immunosuppressive treatment with corticosteroids, mycophenolate mofetil and rituximab.


Assuntos
Terapia Combinada/métodos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Miosite/tratamento farmacológico , Pneumonia/patologia , Administração Intravenosa , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Aminoacil-tRNA Sintetases/imunologia , Autoanticorpos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Pessoa de Meia-Idade , Miosite/imunologia , Miosite/patologia , Pneumonia/etiologia , Rituximab/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Transplant Proc ; 51(6): 1796-1800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399165

RESUMO

BACKGROUND: In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches. METHODS: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model. RESULTS: A total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85-0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79-1.01, P = .05) with 2 HLA-DR mismatches. DISCUSSION: Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.


Assuntos
Incompatibilidade de Grupos Sanguíneos/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DR/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Alemtuzumab/uso terapêutico , Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Soro Antilinfocitário/uso terapêutico , Basiliximab/imunologia , Basiliximab/uso terapêutico , Inibidores de Calcineurina/imunologia , Inibidores de Calcineurina/uso terapêutico , Contraindicações de Procedimentos , Daclizumabe/imunologia , Daclizumabe/uso terapêutico , Bases de Dados Factuais , Feminino , Teste de Histocompatibilidade , Humanos , Rim/imunologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/imunologia , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Resultado do Tratamento
10.
Int Urol Nephrol ; 51(11): 2063-2072, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31385180

RESUMO

PURPOSE: In large observational studies of adult kidney transplant recipients (KTRs) where older adults (65 years old and older) were not well represented, the mammalian target of rapamycin inhibitors (mTOR inhibitors) has poorer outcomes than the standard tacrolimus-mycophenolate-steroids (TAC-MPA-S) regimen. We conducted this study to compare the outcomes of regimens containing the common mTOR inhibitor, sirolimus (SRL) against TAC-MPA-S in older adult KTRs. METHODS: Using the 2000-2016 Scientific Registry of Transplant Recipients, Cox multivariable regression models were conducted to analyze the patient and graft outcomes associated with regimens containing SRL, steroids (S) and cyclosporine (CSA), tacrolimus (TAC), or mycophenolate (MPA) vs. the standard (TAC-MPA-S) regimen in older adult KTRs. RESULTS: Included in the analysis were 15,008 (95.19%) older adult KTRs on standard (TAC-MPA-S) regimen, 242 (1.53%) on SRL-MPA-S, 300 (1.90%) on SRL-TAC-S, and 217 (1.38%) on SRL-CSA-S. Compared with the standard regimen, the adjusted risks of all-cause death and overall graft loss over a maximum 5-year follow-up were highest with SRL-MPA-S, intermediate with SRL-TAC-S and not significantly different with SRL-CSA-S. The adjusted risks of all-cause death and overall graft loss were modified by a pre-transplant history of malignancy in older adult KTRs on SRL-TAC-S, not in those on SRL-MPA-S or SRL-CSA-S. CONCLUSIONS: In older adult kidney transplant recipients, SRL-TAC-S or SRL-MPA-S, but not SRL-CSA-S is associated with higher risks of death and allograft loss than standard TAC-MPA-S regimen and a pre-transplant malignancy history worsens these risks in patients on SRL-TAC-S. Confirmation of our findings by a prospective randomized trial is needed before translation into clinical practice can be recommended.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Sirolimo/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
11.
Transplant Proc ; 51(7): 2295-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400975

RESUMO

PURPOSE: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic anemia, thrombocytopenia, and acute kidney injury. HUS is mostly associated with diarrhea (90%). However, 10% of cases are not associated with diarrhea and are thus called as atypical HUS (aHUS); these cases are usually caused by dysregulation of the complement system. Eculizumab, a monoclonal antibody against C5, is the drug of choice for treating aHUS. Herein we aimed to present 8 cases of renal transplantation performed on patients with aHUS. MATERIALS AND METHODS: A total of 8 patients who had been diagnosed with aHUS between the years 2012 to 2018 were enrolled and underwent transplantations. All patients received induction treatment, standard immunosuppresive treatment (tacrolimus, mycophenolic acid, prednisolone), and eculizumab. Eculizumab was administered at a dosage of 900 mg/wk for the first month and 1200 mg every 2 weeks thereafter. Patients were followed up and recorded in terms of demographic features, serum creatinine, lactate dehydrogenase, acute rejection episodes, and allograft outcomes. RESULTS: Mean age was 34 ± 8 years (Male/Female: 6/2). One of the patients had a second transplantation. Median hemodialysis vintage (25%-75% interquartile range) was 37 (9-63) months. Four patients had pretransplant plasmapheresis and 2 patients had posttransplant plasmapheresis. Induction treatment was ATG in 7 patients, and basiliximab was used only in 1 patient. The median follow-up period was 25 (13-59) months. Mean serum creatinine levels were 1.9 ± .6, 1.2 ± .7, and 1 ± .1 mg/dL for the first day, first month, and last values, respectively. Mean lactate dehydrogenase levels were 286 ± 203, 239 ± 27, and 218 ± 86 U/L for first day, first month, and last values, respectively. None of the patients had an acute rejection episode. Currently, all patients have functioning allografts. CONCLUSION: Patients with aHUS may be transplanted successfully with eculizumab with good allograft outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/cirurgia , Inativadores do Complemento/uso terapêutico , Transplante de Rim , Adulto , Terapia Combinada , Creatinina/análise , Feminino , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Plasmaferese , Período Pós-Operatório , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do Tratamento
12.
Transplant Proc ; 51(7): 2358-2360, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402252

RESUMO

BACKGROUND: In intensive care unit (ICU), although there is no standard protocol for maintenance of immunosuppressive (IS) treatments for the kidney transplant recipients (KTx), the dose and the number of IS drugs are decreased according to the center's experience. The aim of this study is to evaluate the changes in IS treatment during stays in the ICU and to evaluate the safety and results of this modification on the IS treatment in the ICU arbitrarily. METHOD: We evaluated retrospectively our kidney transplant recipients in ICU between 2012 and 2017. The immunosuppressive protocols and the results were taken from the ICU documents. RESULTS: A total of 31 (18 male, 13 female) patients were suitable for the analysis. They were all under the triple IS protocol including Tacrolimus (Tac) + Mycophenolate mofetil (MMF) + steroid before the admission. The reason for ICU admission were severe sepsis in all patients. In ICU, 16 patients (51.6%) died, and a total of 10 patients were lost with functional graft. Change in IS treatment is as follows: a total of the 23 patients (74.2%) were given only steroids, and 8 patients (25.8%) were changed from triple to 2 drugs. Acute kidney injury developed in 42% (13 patients) of the patients in ICU. CONCLUSION: In our study, we observed that life-threatening severe infections were the main cause of ICU admission in KTx. Reduction in IS treatments are common practice, and reduction to a single dose of steroid was the most frequently chosen IS treatment. Eighty percent of patients are discharged with reduction of steroid gradually. None of the patients developed acute rejection and permanent graft injury.


Assuntos
Cuidados Críticos/métodos , Imunossupressores/uso terapêutico , Unidades de Terapia Intensiva/estatística & dados numéricos , Transplante de Rim , Adulto , Protocolos Clínicos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Período Pós-Operatório , Estudos Retrospectivos , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico
13.
Lupus ; 28(9): 1082-1090, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296138

RESUMO

BACKGROUND: Few data are available about the rate of short-term remission and its impact on the long-term outcomes of proliferative lupus nephritis in the Middle East. METHODS: An observational study was carried out involving 96 adult patients with biopsy-proven focal or diffuse proliferative lupus nephritis (PLN) from four different hospitals. Data on induction, remission and long-term outcomes were collected and analyzed. RESULTS: Among the 96 patients with biopsy-proven PLN (median age 27 (IQR: 21,34) years, 85% women and median duration of systemic lupus erythematosus (SLE) prior to diagnosis 27 (IQR: 11, 55) months), 67% developed remission at 6 months (proportion 0.67; 95% CI 0.57, 0.76). Mycophenolate mofetil (MMF) was used in 45/96 (47%), CYC in 41/95 (43%) and other agents in 10/96 (10%). The choice of MMF as induction agent has increased in recent years. Among baseline characteristics, only histologic activity was found to have a significant association with remission, with active lesions more likely to remit than active/chronic and chronic lesions (AOR 6.5, 95% CI 1.44-29.39, p = 0.015). Based on Kaplan-Meier analysis, the 5-year renal survival rate without doubling serum creatinine was 73.8%. Compared to patients with complete remission, lower long-term renal survival rates were observed in patients with no remission (89.7 versus 43%, p = 0.001) and partial remission (89.7 versus 77.6%, p = 0.256). The cumulative rate of doubling serum creatinine, dialysis, relapse and death was 23%, 11%, 10% and 5%, respectively, at 48-month median follow up. CONCLUSION: Approximately two-thirds of patients with PLN develop remission in response to standard induction therapy. Remission was negatively associated with the presence of chronic changes in renal biopsy. Overall, MMF is the most commonly used agent to induce remission; however, with more severe disease CYC, is used more frequently. PLN is associated with significant long-term renal outcomes including a 26% cumulative rate of doubling of serum creatinine at 5 years. Initial remission predicts this long-term renal survival.


Assuntos
Creatinina/sangue , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/tratamento farmacológico , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Medicina (B Aires) ; 79(3): 204-207, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284256

RESUMO

Susac syndrome is a rare disorder caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear. These occlusions lead to a characteristic clinical triad of central nervous system dysfunction, visual disturbances and vestibule-cochlear deficits. The diagnosis is based on clinical manifestations and complementary studies, which demonstrate the involvement of three systems. There are different treatments that include various immunosuppressive drugs combinations such as corticosteroids, intravenous immunoglobulin, mycophenolate mofetil, among others. We present the case of a 26-year-old woman with left hearing loss, tinnitus and episodes of recurrent vertigo, four weeks after bilateral blurred vision, cerebellar ataxia and encephalopathy. Magnetic resonance imaging of the brain showed multiple rounded hyperintense lesions in t2 and fluid-attenuated inversion recovery (FLAIR), hypointense in t1, at the middle level of the corpus callosum, internal capsule, cerebellum and right middle cerebellar peduncle. The audiometry evidenced bilateral perceptual hearing loss, predominantly in the left ear. Angiography by optical coherence tomography showed obstruction in the deep layer retina arteries. The Susac syndrome was diagnosed and treatment started with methylprednisolone pulses therapy, intravenously 1000 mg/day for 5 days, followed by maintenance with mycophenolate, which completely reversed the encephalopathy, with persistence of mild ataxia and hearing loss. It is important to know the clinical triad characteristic and the complementary studies necessary to arrive at the diagnosis, since immunosuppressive treatment can often be delayed. Our case had an excellent response to corticosteroids.


Assuntos
Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Síndrome de Susac/complicações , Síndrome de Susac/diagnóstico por imagem , Vertigem/diagnóstico , Anti-Inflamatórios/uso terapêutico , Encefalopatias/tratamento farmacológico , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Feminino , Humanos , Imagem por Ressonância Magnética , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Fármacos Neuroprotetores , Prednisolona/uso terapêutico , Gravidez , Síndrome de Susac/tratamento farmacológico
15.
Transplant Proc ; 51(8): 2602-2605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31324482

RESUMO

BACKGROUND: Rabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation. METHODS: Between April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function. RESULTS: A total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration. CONCLUSIONS: rATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Rim , Adulto , Basiliximab/uso terapêutico , Feminino , Rejeição de Enxerto/imunologia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Plasmaferese/métodos , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Resultado do Tratamento
16.
Drug Des Devel Ther ; 13: 2187-2193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308630

RESUMO

Background: Tablet and capsule forms have advantages and disadvantages in the market. Generally, the tablet form (500 mg) of mycophenolate mofetil (MMF) is more convenient for drug ingestion and more cost-effective than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in liver transplant recipients. Methods: A randomized controlled trial was performed to compare the efficacy and safety between the tablet form of MMF (tablet group) and the capsule form of MMF (capsule group) in liver transplant patients. One hundred sixteen patients were enrolled in the present study from 2014 to 2017. Fifty-six patients in the full-analysis set (FAS) population were in the capsule group and 60 were in the tablet group. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) by 24 weeks after liver transplantation (LT). Secondary endpoints were patient survival, serum creatinine level, and adverse events (AEs). Results: In the per-protocol population, 45 patients were in the tablet group and 49 were in the capsule group. There were no statistically significant differences in MMF dose, mycophenolic acid trough level, and tacrolimus trough level between the two groups. The incidence of BPAR at 24 weeks after randomization was 6.7% in the tablet group and 6.1% in the capsule group (P=0.627). All patients with BPAR responded well to steroid pulse therapy and increased tacrolimus. Serum creatine level and eGFR were not different between the two groups. The incidence of serious AEs was 7.2% in the tablet group and 7.6% in the capsule group, and none were related to formulation. There was no significant difference in incidence of discontinuations or serious AEs between the two groups. Conclusion: The present study suggests that the new tablet formulation can be a useful treatment option to maintain a consistent systemic exposure level of MMF, which may help reduce graft failure in liver transplant patients.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transplante de Fígado , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Adulto , Idoso , Cápsulas , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Comprimidos , Adulto Jovem
17.
Curr Opin Ophthalmol ; 30(5): 401-406, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313753

RESUMO

PURPOSE OF REVIEW: To offer an update on advances and controversies in the assessment, investigation and treatment of thyroid eye disease (TED), a disfiguring orbital autoimmune disease, which can manifest with diplopia and threaten not only sight - but also life. RECENT FINDINGS: Developments in biomarkers and imaging are helping to tailor the management of patients. Emerging therapies target different pathways in the disease and are informed by studies into TED pathogenesis: the last 2 years has, for example, seen the culmination of a two-decade long bench-to-bedside story in which an original focus on the IGF1 receptor has translated into an effective treatment for proptosis in thyroid eye disease. Whether this will result in a real-world reduction in TED-related morbidity will depend on access; commercial pricing decisions may preclude widespread adoption of novel therapies. SUMMARY: Thyroid eye disease research is enjoying a renaissance with advances in both monitoring and treatment coupled with a renewed emphasis on a holisitic approach, which includes aesthetic care for patients; this is perhaps the most exciting time to be part of the international thyroid eye disease community in decades - for physicians, surgeons and patients. The commercial window for break-through drugs are narrowing with an array of new therapeutic agents in the pipeline over the coming decade.


Assuntos
Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Descompressão Cirúrgica , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Sirolimo/uso terapêutico
18.
J Korean Med Sci ; 34(27): e185, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31293110

RESUMO

BACKGROUND: The objective of this study was to identify the effects of mycophenolate mofetil (MMF) on non-renal manifestations in systemic lupus erythematosus (SLE). METHODS: The study population comprised 439 SLE patients from the Korean Lupus Network registry who were followed up annually and completed the baseline survey and two follow-up visits from 2014 to 2018. Disease activity, laboratory markers, and clinical manifestations including mucocutaneous lesions, arthritis, serositis, neurological disorders, and hematologic/immunologic abnormalities were assessed. All variables by group (MMF and non-MMF) effects with time (baseline, 1st follow-up, and 2nd follow-up) were analyzed by generalized estimation equation. RESULTS: Seventy-two patients were treated with MMF. There was significant difference in frequencies of malar rash, arthritis, renal disorder, and hematologic disorder between MMF and non-MMF groups in total SLE patients. In subgroup analysis of hematologic abnormalities in total patients, frequency of leukopenia was significantly different between the two groups during follow-up (P = 0.001), but frequencies of hemolytic anemia, lymphopenia, and thrombocytopenia were not. In addition, frequencies of leukopenia in patients without lupus nephritis were significantly decreased in MMF group compared to non-MMF group (P = 0.012). CONCLUSION: This study showed that MMF might be a beneficial treatment for hematologic abnormalities, especially leukopenia, in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adulto , Depressão/complicações , Depressão/diagnóstico , Exantema/etiologia , Feminino , Doenças Hematológicas/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Qualidade de Vida , Sistema de Registros , República da Coreia
19.
Acta Reumatol Port ; 44(2): 161-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280278

RESUMO

Interstitial lung disease (ILD) is one of the major causes of morbidity and mortality in patients with connective tissue disease (CTD) and the treatments available until nowadays are in most cases unable to halt disease progression. CTD-ILD pathogenesis includes an initial inflammatory phase, followed by a fibrotic phase, in which extracellular matrix proteins are produced and fibrotic scaring tissue within the lung develops. Steroids and immunosuppressants are the weapons we currently have to treat CTD-ILD. However, mortality rates remain high and identification of new therapeutic targets is crucial. Antifibrotic drugs, which include nintedanib and pirfenidone, have been approved for the treatment of idiopathic pulmonary fibrosis (IPF) and due to similar pathogenesis between IPF and CTD-ILD, their use seems attractive in patients with CTD-IL. We report 3 cases of patients with different CTDs, with predominantly fibrotic changes in high resolution computed tomography that progressed despite immunosuppression, and who have attained disease stability after introduction of antifibrotic drugs.


Assuntos
Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Piridonas/uso terapêutico , Escleroderma Sistêmico/complicações , Síndrome de Sjogren/complicações , Idoso , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Substituição de Medicamentos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Infliximab/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Resultado do Tratamento
20.
Lupus ; 28(8): 954-960, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31221051

RESUMO

BACKGROUND: Blood pressure visit-to-visit variability is a novel risk factor for deleterious long-term cardiac and renal outcomes in the general population. We hypothesized that patients with systemic lupus erythematosus (SLE) have greater blood pressure visit-to-visit variability than control subjects and that blood pressure visit-to-visit variability is associated with a higher comorbidity burden. METHODS: We studied 899 patients with SLE and 4172 matched controls using de-identified electronic health records from an academic medical center. We compared blood pressure visit-to-visit variability measures in patients with SLE and control subjects and examined the association between blood pressure visit-to-visit variability and patients' characteristics. RESULTS: Patients with SLE had higher systolic blood pressure visit-to-visit variability 9.7% (7.8-11.8%) than the control group 9.2% (7.4-11.2%), P < 0.001 by coefficient of variation. Additional measures of systolic blood pressure visit-to-visit variability (i.e. standard deviation, average real variation, successive variation and maximum measure-to-measure change) were also significantly higher in patients with SLE than in control subjects. In patients with SLE, blood pressure visit-to-visit variability correlated significantly with age, creatinine, CRP, triglyceride concentrations and the Charlson comorbidity score (all P < 0.05). Hydroxychloroquine use was associated with reduced blood pressure visit-to-visit variability (P < 0.001), whereas the use of antihypertensives, cyclophosphamide, mycophenolate mofetil and corticosteroids was associated with increased blood pressure visit-to-visit variability (P < 0.05). CONCLUSION: Patients with SLE had higher blood pressure visit-to-visit variability than controls, and this increased blood pressure visit-to-visit variability was associated with greater Charlson comorbidity scores, several clinical characteristics and immunosuppressant medications. In particular, hydroxychloroquine prescription was associated with lower blood pressure visit-to-visit variability.


Assuntos
Comorbidade , Hidroxicloroquina/uso terapêutico , Hipertensão/epidemiologia , Inflamação/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , Ciclofosfamida/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Modelos Logísticos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença
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