Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study

Stallmach, Andreas; Langbein, C.; Atreya, Raja; Bruns, Tony; Dignaß, Axel; Ende, K; Hampe, Jochen; Hartmann, Franz; Neurath, Markus F.; Maul, Jochen; Preiß, J; Schmelz, Renate; Siegmund, Britta; Schulze, H; Teich, Niels; Arnim, Ulrike von; Baumgart, Daniel C.; Schmidt, Carsten

doi:10.1111/apt.13813

Cited by 150 publications

(145 citation statements)

References 34 publications

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“…Although controlled clinical trials suggested that vedolizumab might induce more rapid clinical remis sion in ulcerative colitis than in Crohn's disease 59,60 , sub sequent real world data confirmed efficacy of this drug for moderate-severe Crohn's disease in routine clinical practice 64 with similar rates of long term remission in Crohn's disease and ulcerative colitis 65 . The reasons for potential differences between vedolizumab in Crohn's disease versus ulcerative colitis remain to be deter mined.…”

Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

513

403

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Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

513

403

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“…Clinical response to vedolizumab at week 10 was observed in 46% of these patients. In a real-world scenario, vedolizumab was found effective to induce clinical remission at week 54 in 25% of patients [8]; a further study showed a slightly greater remission rate of 35% after a median follow-up of 39 weeks [18]. Both cohorts covered ≥90% of patients that were TNF antagonist experienced.…”

Section: Discussionmentioning

confidence: 99%

“…Further therapeutic options were opened by the introduction of vedolizumab and ustekinumab, monoclonal antibodies against α4β7 integrin and interleukin 12/23p40. With respect to the TNF failure cohort of CD patients, retrospective data of real-world experience showed an initial clinical response to vedolizumab in about 60% and remission rates at week 54 between 21 and 25% [8]. A response to ustekinumab was demonstrated in 58% of patients [9].…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

Bär

Krause²,

Stallmach

et al. 2017

Inflamm Intest Dis

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Background and Aims: In Crohn's disease (CD) patients still remain refractory to current regimens, including biologicals. Previous data from small single-center studies indicated cyclophosphamide pulse therapy (CPT) to be effective for induction of remission at least in steroid-refractory cases. The aim of the present study was to study the efficacy and safety of CPT in mainly tumor necrosis factor (TNF)-refractory complicated CD patients. Methods: Patients with refractory CD undergoing CPT were identified in 13 centers of the German IBD Study Group and retrospectively registered. In total, 41 patients (12 male, 29 female, median age 36 years, range 18-72 years) were included for analysis. Seventy-eight percent of these had previously been treated with thiopurines and 90% had previously received anti-TNF antibodies. Former steroid treatment was found throughout the cohort. Results: Patients received a median number of 5 (1-13) pulses every 28 (13-54) days in a period of 120 (12-411) days. A median dose of 766 (600-1,200) mg and a median cumulative dose of 4,500 (750-9,750) mg was given. A clinical response (reduction in the Harvey-Bradshaw Index [HBI] ≥2 points) was found in 68% of the patients and clinical remission (HBI <5 points) in 32%. Steroids could be reduced from 31 to 12 mg per day over all patients. Side effects were recorded in 71% (n = 29) of the patients. Three patients terminated CPT due to side effects. No patient died. Conclusion: Our data point to CPT as a therapeutic alternative for induction of remission in patients with severe refractory courses of CD including TNF antagonists. CPT might serve as bridging for maintenance treatment.

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“…A German prospective study assessing the efficacy of vedolizumab induction therapy showed clinical remission at week 14 in 23.7% of the patients with Crohn's disease and 23.5% of the patients with ulcerative colitis [8]. In this patient group, clinical remission was achieved after 54 weeks in 21% of the patients with Crohn's disease and 25% of the patients with ulcerative colitis [9]. Recently, a French prospective study including 173 patients with Crohn's disease and 121 with ulcerative colitis found that up to one-third of the patients were in steroid-free clinical remission at week 54 of vedolizumab therapy, but a significant number of patients experienced a loss of response during the first year of treatment [10].…”

Section: Doi: 101159/000492322mentioning

confidence: 87%

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn’s Disease at a Tertiary Referral Center

Hoffmann

Krisam

Stremmel

et al. 2018

Dig Dis

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Background: Vedolizumab was approved for the therapy of ulcerative colitis and Crohn’s disease in mid-2014. Real-world treatment data are necessary for a balanced assessment of its position among other therapeutic options. Summary: Patients with ulcerative colitis or Crohn’s disease, initiating vedolizumab therapy at the outpatient clinic for inflammatory bowel diseases at the University Hospital Heidelberg between June 1, 2014 and August 31, 2016, were recruited based on electronic medical records. The primary study endpoint was response at week 30, while the secondary endpoints were the need for surgery and discontinuation of therapy due to inadequate response, or adverse events. Twenty-five patients with ulcerative colitis (40% anti-tumor necrosis factor α [TNFα] naive) and 28 patients with Crohn’s disease (10.7% anti-TNFα naive, 53.6% having undergone at least one intestinal surgery) were enrolled. Among the ulcerative colitis patients, 20% achieved remission, 32% partial response, and 48% were non-responders to vedolizumab. In Crohn’s disease, 14.3% of the patients achieved remission, 46.4% partial response, and 39.4% were non-responders. Two patients discontinued vedolizumab therapy due to suspected side effects. Key Message: In a relatively treatment-refractory cohort of inflammatory bowel disease patients, vedolizumab was efficacious in achieving response. However, the majority of the patients were not satisfactorily treated, as they did not reach remission.

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Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study

Abstract: Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

Cited by 150 publications

References 34 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn’s Disease at a Tertiary Referral Center

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