Safety and tolerability of concurrent natalizumab treatment for patients with Crohnʼs disease not in remission while receiving infliximab

Sands, Bruce E.; Kozarek, Richard A.; Spainhour, Jack B.; Barish, Charles F.; Becker, Scott; Goldberg, Lawrence; Katz, Seymour; Goldblum, R. M.; Harrigan, Rena; Hilton, Deborah J; Hanauer, Stephen B.

doi:10.1002/ibd.20014

Cited by 145 publications

(90 citation statements)

References 17 publications

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“…Interestingly, a drug called natalizumab, which has been used to treat autoimmune diseases such as multiple sclerosis and inflammatory bowel disease (50,51), is believed to function by blocking the ␣ 4 subunit of both CD49d (␣ 4 ␤ 1 ) and ␣ 4 ␤ 7 . Th17 cells have recently been shown to play a similar or increased role, compared with Th1 cells, in these two diseases (52).…”

Section: Discussionmentioning

confidence: 99%

Both Th1 and Th17 Are Immunopathogenic but Differ in Other Key Biological Activities

Cox

Shi²,

Yin³

et al. 2008

The Journal of Immunology

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The role of Th17 lymphocytes in immunopathogenic processes has been well established, but little is known about their basic cell features. In this study, we compared polarized Th1 and Th17 for key biological activities related to pathogenicity and trafficking. Th1 and Th17 lineages were derived from TCR-transgenic CD4 murine cells specific against hen egg lysozyme. When adoptively transferred into mice expressing hen egg lysozyme in their eyes, both Th1 and Th17 induced ocular inflammation but with slight differences in histological pathology. PCR analysis revealed selective expression of IFN-γ or IL-17 in eyes of Th1 or Th17 recipients, respectively. Additionally, Th1 and Th17 were found to differ in three other key activities: 1) Th17 cells were inferior to Th1 cells in their capacity to trigger massive lymphoid expansion and splenomegaly; 2) the proportion of Th1 cells among infiltrating cells in inflamed recipient eyes declined rapidly, becoming a minority by day 7, whereas Th17 cells remained in the majority throughout this period; and 3) remarkable differences were noted between Th1 and Th17 cells in their expression of certain surface markers. In particular, reactivated Th1 expressed higher levels of CD49d and α4β7 (mucosal homing) in vitro and higher levels of CXCR3 (Th1 trafficking) in vivo. Reactivated Th17, however, expressed higher levels of αEβ7 (epithelial tissue homing) and CD38 (activation, maturation and trafficking) in vitro, but in vivo Th17 expressed higher levels of α4β7 and CCR6 (lymphocyte trafficking). These data reveal that Th1 and Th17 cells differ in several key biological activities influencing migration and pathogenic behavior during inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

Both Th1 and Th17 Are Immunopathogenic but Differ in Other Key Biological Activities

Cox

Shi²,

Yin³

et al. 2008

The Journal of Immunology

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“…Adverse events Natalizumab has demonstrated a consistent safety profile within controlled clinical trials of CD, with the most frequently reported (!10%) adverse events (AEs) including headache, fatigue, upper respiratory tract infections, and nausea [Elan Pharmaceuticals and Biogen Idec, 2010;Sands et al 2007;Targan et al 2007;Sandborn et al 2005;Ghosh et al 2003;Gordon et al 2001]. The most frequently reported AEs that resulted in discontinuation of natalizumab were exacerbation of CD (4.2%) and acute hypersensitivity reactions (1.5%).…”

Section: Safetymentioning

confidence: 99%

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Ghosh

Panaccione

2010

Therap Adv Gastroenterol

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Although biologic agents directed against tumor necrosis factor alpha (TNFa) continue to be an effective therapeutic strategy for patients with inflammatory bowel disease (IBD), approximately 30% of patients with Crohn's disease (CD) who are refractory to standard treatment do not respond to induction therapy with TNFa inhibitors and, of those who initially respond, 50% or more cease to respond within a year. Moreover, their use can be associated with significant safety issues. Clearly, there is a need to target alternative pathways involved in the inflammatory process. IBD is driven by the trafficking of lymphocytes from the circulation into the gut tissue that is mediated by adhesive interactions between the lymphocytes and endothelial cells. The adhesion molecules involved represent attractive targets for the development of new therapeutics which should aid in the resolution of existing inflammation, prevent recurrence of inflammation, and may potentially lead to long-term control of disease. In this article we review current opportunities and challenges facing anti-adhesion therapy in IBD, and discusses recent clinical development efforts that have focused on having an impact on two particular adhesive interactions: a 4 -integrin/MAdCAM-1 and b 2 -integrin/ICAM-1. Of particular interest is natalizumab, a humanized monoclonal antibody against human a 4 integrin that is approved for the treatment of patients with moderately-to-severely active CD and evidence of active inflammation. This agent represents an efficacious therapeutic option for patients who do not respond to, or have failed, a TNF-a inhibitor.

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“…Natalizumab usado como monoterapia en dosis de 300 mg cada 4 semanas ha demostrado ser efectivo y seguro en EC refractaria a agentes anti-TNF [9][10][11][12][13][14][15][16][17] . Además, este fármaco ha demostrado ser eficaz en población pediátrica con EC con tasas de remisión clínica de 50% 18 .…”

Section: Discussionunclassified

“…Natalizumab es un anticuerpo monoclonal IgG4 anti-integrina-α4 humanizado que bloquea la adhesión y migración de leucocitos desde los vasos sanguíneos al tejido inflamado 7,8 . Este fármaco ha mostrado ser efectivo en inducir y mantener la remisión en pacientes con EC [9][10][11][12][13][14][15][16][17][18] . Sin embargo, su uso se ha visto limitado por reportes que han descrito el desarrollo de leucoencefalopatía multifocal progresiva (LMP), infección oportunista fatal causada por la reactivación del virus latente John Cunningham (JC), en pacientes con EC y esclerosis múltiple (EM) tratados con natalizumab 19,20 .…”

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Experiencia local con natalizumab en pacientes con enfermedad de Crohn refractaria a anti-TNF: Casos clínicos

et al. 2017

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Natalizumab for the treatment of Crohn's disease. Report of three cases . Aunque la incidencia y prevalencia de la EC en Chile es aún desconocida, recientemente demostramos que el número de casos ha aumentado durante las últimas décadas 2 . Los objetivos terapéuticos son disminuir la inflamación e inducir la remisión clínica, endoscópica y radiológica de la enfermedad. Para lograr esto, la estrategia más efectiva es el uso de terapia biológica (TB) dado su rol en neutralizar vías inmunológicas específicas involucradas en el desarrollo y evolución de la EC. En la última década, los anticuerpos anti-factor de necrosis tumoral-α (anti-TNF) (infliximab, adalimumab y certolizumab) han sido la TB más utilizada en lograr la inducción y mantención de la remisión en pacientes con EC moderada-severa 2,3 . Sin embargo, aproximadamente 30-40% de los pacientes no responderán a la terapia de inducción (no-respondedores primarios) y hasta un 50% perderán respuesta durante la fase de mantención (no-respondedores secundarios) siendo necesario intensificar el tratamiento (aumentar la dosis o Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn's Disease (CD

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Safety and tolerability of concurrent natalizumab treatment for patients with Crohnʼs disease not in remission while receiving infliximab

Abstract: The combination of natalizumab plus infliximab was well tolerated. Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone.

Cited by 145 publications

References 17 publications

Both Th1 and Th17 Are Immunopathogenic but Differ in Other Key Biological Activities

Both Th1 and Th17 Are Immunopathogenic but Differ in Other Key Biological Activities

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Experiencia local con natalizumab en pacientes con enfermedad de Crohn refractaria a anti-TNF: Casos clínicos

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