RESUMO
BACKGROUND: Real-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn's disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany. METHODS: A retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding [RB], stool frequency [SF]; CD: abdominal pain [AP], liquid stools [LS]) and outcome duration. RESULTS: A total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively. CONCLUSIONS: Although there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.
Assuntos
Colite Ulcerativa , Doença de Crohn , Anticorpos Monoclonais Humanizados , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Alemanha , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Extraintestinal manifestations [EIMs] such as arthritis/arthralgia are common in inflammatory bowel disease. We performed post hoc analyses of data from the GEMINI studies to evaluate the effect of vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia. METHODS: Sustained resolution of baseline arthritis/arthralgia, worsening of baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling was used for time-to-event analysis. The influence of corticosteroid-tapering was also investigated. RESULTS: In Crohn's disease [CD] patients, vedolizumab was significantly less likely than placebo to be associated with new/worsening arthritis/arthralgia (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89). Similar incidences of sustained resolution of arthritis/arthralgia occurred with vedolizumab and placebo. In CD patients on corticosteroids at baseline, a decrease in corticosteroid dose increased the risk of new/worsening arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of treatment; and in those achieving corticosteroid-free status, arthritis/arthralgia was less likely with vedolizumab than with placebo [HR, 0.14; 95% CI, 0.05-0.35]. In ulcerative colitis [UC] patients, vedolizumab and placebo showed a similar incidence of new/worsening of arthritis/arthralgia. In UC patients on corticosteroid at baseline, arthritis/arthralgia was more likely in those achieving corticosteroid-free status than in those continuing corticosteroids (HR 2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status, the incidence of arthritis/arthralgia was similar with vedolizumab and placebo. CONCLUSIONS: Vedolizumab therapy was associated with a reduced likelihood of new/worsening arthritis/arthralgia in CD and no increased incidence of these events in UC. STUDIES INCLUDED [CLINCIALTRIALS.GOV, NUMBER]: GEMINI 1 [NCT00783718]; GEMINI 2 [NCT00783692]; GEMINI 3 [NCT01224171].
Assuntos
Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artralgia/epidemiologia , Artrite/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Progressão da Doença , Humanos , IncidênciaRESUMO
OBJECTIVE: Symptomatic infections of the central nervous system (CNS) with JC polyomavirus (JCV) usually occur as a result of immunocompromise and manifest as progressive multifocal leukoencephalopathy (PML) or granule cell neuronopathy (GCN). After immune reconstitution, some of these cases may show long-term persistence of JCV and delayed clinical improvement despite inflammation. METHODS: We followed 4 patients with multiple sclerosis, who developed natalizumab-associated PML or GCN with regard to JC viral load and JCV-specific T-cell responses in the CNS. All of them experienced immune reconstitution inflammatory syndrome (IRIS), but in 2 cases JCV persisted > 21 months after IRIS accompanied by delayed clinical improvement. RESULTS: Persistence of JCV was associated with a lack of JCV VP1-specific T-cell responses during immune reconstitution in 1 of the patients. Detailed analysis of the brain infiltrate in another patient with neuronal persistence of JCV revealed strong infiltration of CD8(+) T cells and clonal expansion of activated CD8(+) effector T cells with a CD4(dim) CD8(+) phenotype, both exhibiting exquisite specificity for conserved epitopes of JCV large T antigen. However, clearance of JCV was not efficient, because mutations in the major capsid protein VP1 caused reduced CD4(+) T-cell responses against the identified JCV variant and subsequently resulted in a decline of CD8(+) T-cell responses after IRIS. INTERPRETATION: Our findings suggest that efficient CD4(+) T-cell recognition of neurotropic JCV variants is crucial to support CD8(+) T cells in combating JCV infection of the CNS.
Assuntos
Evasão da Resposta Imune/imunologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , Vírus JC/fisiologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/virologia , Esclerose Múltipla/imunologia , Adulto , Encéfalo/imunologia , Encéfalo/virologia , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/virologia , Vírus JC/classificação , Vírus JC/genética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/virologiaRESUMO
Posttransplant lymphoproliferative disorder (PTLD) involves uncommon, severe complications following the transplantation of solid organs, bone marrow and stem cells. Despite comprising mainly lymphoid proliferations that are predominantly driven by lymphotropic Epstein-Barr virus (EBV) infections, PTLD often displays substantial morphologic heterogeneity that can pose diagnostic challenges. With the steady increase in transplantations accompanied by potent immunosuppressive therapy, it is important to heighten awareness of this entity among clinicians and pathologists. In comparison to systemic PTLD, cases that primarily manifest in the central nervous system (CNS) are reported to be more severe and to exhibit unique characteristics. So far, only isolated cases and small series have been reported describing CNS involvement in PTLD. In this article, we review the current knowledge, focusing on the histopathological features of primary CNS lymphoproliferative disorders following organ transplantation.
Assuntos
Encéfalo/patologia , Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Encéfalo/fisiopatologia , Diagnóstico Diferencial , Humanos , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapiaRESUMO
Progressive multifocal leukoencephalopathy is the most common clinical presentation of JC virus (JCV)-associated central nervous system (CNS) disease and has emerged as a major safety concern in multiple sclerosis patients treated with the monoclonal antibody natalizumab. Here we report clinical, radiological, and histological findings of a case of cerebellar granule cell neuronopathy (GCN), a JCV-associated CNS disease, so far unreported amongst patients treated with natalizumab. GCN should be considered as a JCV CNS manifestation in patients with newly developed, progressive cerebellar signs under natalizumab treatment, especially in cases where cerebellar atrophy can be visualized by magnetic resonance imaging.