In the Journals

Entyvio shows favorable long-term safety profile in IBD patients

Entyvio was shown to have low incidence rates of serious infections, infusion-related reactions and malignancies in long-term treatment of patients with ulcerative colitis or Crohn’s disease in a recent study.

Entyvio (vedolizumab, Takeda) “is a monoclonal antibody that targets the [alpha-4/beta-7] integrin and selectively prevents the infiltration of leukocytes into the gastrointestinal submucosa. It is thus an almost ‘gut-selective’ agent as opposed to previous biologics which have a more systemic effect,” Jean-Frédéric Colombel, MD, director of the Susan and Leonard Feinstein IBD Clinical Center at Mount Sinai, New York, told Healio Gastroenterology. “This paper reviewed all safety data of vedolizumab across all available clinical trials.”

Jean-Frédéric Colombel

Six double-blind or open-label trials of vedolizumab in patients with UC or CD were performed from May 2007 to June 2013, and within the safety population, 2,830 patients received at least one dose of vedolizumab, corresponding to 4,811 person-years of exposure (median exposure range, 1-1,977 days).

Vedolizumab exposure was not found to be associated with increased risk for infection or serious infection. Serious clostridial infections, sepsis, tuberculosis and Listeria meningitis were reported in no more than 0.6% of patients. Moreover, no confirmed cases of progressive multifocal leukoencephalopathy occurred.

Independent risk factors for serious infections in UC included previous anti–TNF-alpha failure (HR = 1.99; 95% CI, 1.16-3.42) and concomitant use of narcotic analgesics (HR = 2.68; 95% CI, 1.57-4.58). Independent risk factors for serious infections in CD included younger age (HR = 0.97; 95% CI, 0.95-0.98), concomitant use of corticosteroids (HR = 1.88; 95% CI, 1.35-2.63) and concomitant use of narcotic analgesics (HR = 2.72; 95% CI, 1.9-3.89).

No more than 5% of patients in each study who were exposed to vedolizumab experienced an infusion-related reaction as defined by study investigators, and fewer than 1% of patients who were exposed to vedolizumab were diagnosed with a malignancy.

“The rate of malignancy (0.1/100 person-years) was consistent with that observed in patients with IBD normally,” Colombel said. “In conclusion, a favorable benefit-risk profile makes vedolizumab a useful option for the long-term treatment of IBD. Still appropriate long-term registries are needed to fully assess the safety profile of the drug in clinical practice.” – by Adam Leitenberger

Disclosure: Colombel reports he has served as consultant, advisory board member or speaker for AbbVie, ABScience, Amgen, Bristol-Myers Squibb, Celltrion, Danone, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune Pharmaceuticals, MedImmune, Merck & Co, Millennium Pharmaceuticals, Neovacs, Nutrition Science Partners, Pfizer, Prometheus Laboratories, Protagonist, Receptos, Sanofi, Schering Plough Corporation, Second Genome, Shire, Takeda, Teva Pharmaceuticals, Tigenix, UCB Pharma, and Vertex. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Entyvio was shown to have low incidence rates of serious infections, infusion-related reactions and malignancies in long-term treatment of patients with ulcerative colitis or Crohn’s disease in a recent study.

Entyvio (vedolizumab, Takeda) “is a monoclonal antibody that targets the [alpha-4/beta-7] integrin and selectively prevents the infiltration of leukocytes into the gastrointestinal submucosa. It is thus an almost ‘gut-selective’ agent as opposed to previous biologics which have a more systemic effect,” Jean-Frédéric Colombel, MD, director of the Susan and Leonard Feinstein IBD Clinical Center at Mount Sinai, New York, told Healio Gastroenterology. “This paper reviewed all safety data of vedolizumab across all available clinical trials.”

Jean-Frédéric Colombel

Six double-blind or open-label trials of vedolizumab in patients with UC or CD were performed from May 2007 to June 2013, and within the safety population, 2,830 patients received at least one dose of vedolizumab, corresponding to 4,811 person-years of exposure (median exposure range, 1-1,977 days).

Vedolizumab exposure was not found to be associated with increased risk for infection or serious infection. Serious clostridial infections, sepsis, tuberculosis and Listeria meningitis were reported in no more than 0.6% of patients. Moreover, no confirmed cases of progressive multifocal leukoencephalopathy occurred.

Independent risk factors for serious infections in UC included previous anti–TNF-alpha failure (HR = 1.99; 95% CI, 1.16-3.42) and concomitant use of narcotic analgesics (HR = 2.68; 95% CI, 1.57-4.58). Independent risk factors for serious infections in CD included younger age (HR = 0.97; 95% CI, 0.95-0.98), concomitant use of corticosteroids (HR = 1.88; 95% CI, 1.35-2.63) and concomitant use of narcotic analgesics (HR = 2.72; 95% CI, 1.9-3.89).

No more than 5% of patients in each study who were exposed to vedolizumab experienced an infusion-related reaction as defined by study investigators, and fewer than 1% of patients who were exposed to vedolizumab were diagnosed with a malignancy.

“The rate of malignancy (0.1/100 person-years) was consistent with that observed in patients with IBD normally,” Colombel said. “In conclusion, a favorable benefit-risk profile makes vedolizumab a useful option for the long-term treatment of IBD. Still appropriate long-term registries are needed to fully assess the safety profile of the drug in clinical practice.” – by Adam Leitenberger

Disclosure: Colombel reports he has served as consultant, advisory board member or speaker for AbbVie, ABScience, Amgen, Bristol-Myers Squibb, Celltrion, Danone, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen, Immune Pharmaceuticals, MedImmune, Merck & Co, Millennium Pharmaceuticals, Neovacs, Nutrition Science Partners, Pfizer, Prometheus Laboratories, Protagonist, Receptos, Sanofi, Schering Plough Corporation, Second Genome, Shire, Takeda, Teva Pharmaceuticals, Tigenix, UCB Pharma, and Vertex. Please see the full study for a list of all other researchers’ relevant financial disclosures.

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