Etrolizumab for the Treatment of Ulcerative Colitis and Crohn’s Disease: An Overview of the Phase 3 Clinical Program

Sandborn, William J.; Vermeire, Séverine; Tyrrell, Helen E.J.; Hassanali, Azra; Lacey, Stuart R.; Tole, Swati; Tatro, Amanda R.

doi:10.1007/s12325-020-01366-2

Cited by 66 publications

(63 citation statements)

References 37 publications

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“…After 10 weeks of therapy, clinical remission was achieved in 18.4 vs. 6.0% (p 0.001) of the study participants, respectively; clinical remission was associated with a higher rate of mucosal healing. In the maintenance study that followed, 37% of the patients, that initially responded to the induction therapy reached a clinical remission after 52 weeks, compared to only 18.5% of those receiving placebo (p < 0.001) (Danese et al, 2020b;Sandborn et al, 2020f).…”

Section: Modulation Of Sphingosine-1-phosphate Receptorsmentioning

confidence: 99%

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians’ Perspective

2021

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The introduction of anti-tumor necrosis factor antibodies resulted in a considerable expansion of the options available for the treatment of inflammatory bowel disease. Unfortunately, approximately one third of treated patients do not respond to these modalities, and drug efficacy may be lost over time. These drugs are also associated with contraindications, adverse events, and intolerance. As such, there is an ongoing need for new therapeutic strategies. Despite several recent advances, including antibodies against pro-inflammatory cytokines and cell adhesion molecules, Janus kinase inhibitors, and modulators of sphingosine-1-phosphate receptors, not all problems associated with IBD have been solved. In this manuscript, we review the current state of development of several new treatment options. Ongoing evaluation will require specific proof of efficacy as well as direct comparisons with established treatments. Results from head-to-head comparisons are needed to provide clinicians with critical information on how to formulate effective therapeutic approaches for each patient.

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Section: Modulation Of Sphingosine-1-phosphate Receptorsmentioning

confidence: 99%

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians’ Perspective

2021

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“…While VDZ targets only the α4β7 integrin, etrolizumab is a SC humanized monoclonal anti-integrin antibody that selectively binds the β7 subunit of both α4β7 and αEβ7 integrins (Vermeire et al, 2014;Sandborn et al, 2020h). Therefore, etrolizumab controls movement of inflammatory cells into the gastrointestinal tract and also mediates inflammatory effects on the gut mucosa (Vermeire et al, 2014;Sandborn et al, 2020h). The phase II EUCALYPTUS study showed that etrolizumab was beneficial over placebo in patients with moderate-severe UC (Vermeire et al, 2014).…”

Section: Etrolizumabmentioning

confidence: 99%

“…The aim of HIBISCUS I and II (identical induction trials of etrolizumab 105 mg vs. adalimumab and placebo), GARDENIA (maintenance study studying etrolizumab 105 mg vs. infliximab), and LAUREL (maintenance trial evaluating etrolizumab 105 mg against placebo) is to study UC patients who are anti-TNF naïve. HICKORY is a maintenance trial studying etrolizumab 105 mg vs. placebo in anti-TNF exposed UC patients (Sandborn et al, 2020h). The primary endpoints are based on clinical response (≥3 point decrease and 30% reduction in Mayo clinic score and ≥1 point decrease in rectal bleeding or an absolute rectal bleeding score of 0 or 1), remission (MCS ≤2, with individual subscore ≤1 and rectal bleeding score of 0) at each trial's specified time points (Sandborn et al, 2020h).…”

Section: Etrolizumabmentioning

confidence: 99%

“…HICKORY is a maintenance trial studying etrolizumab 105 mg vs. placebo in anti-TNF exposed UC patients (Sandborn et al, 2020h). The primary endpoints are based on clinical response (≥3 point decrease and 30% reduction in Mayo clinic score and ≥1 point decrease in rectal bleeding or an absolute rectal bleeding score of 0 or 1), remission (MCS ≤2, with individual subscore ≤1 and rectal bleeding score of 0) at each trial's specified time points (Sandborn et al, 2020h). COTTONWOOD is the open-label extension and safety monitoring study of UC patients treated with etrolizumab who were followed until week 108 (Sandborn et al, 2020h).…”

Section: Etrolizumabmentioning

confidence: 99%

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Novel and Emerging Therapies for Inflammatory Bowel Disease

2021

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Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and to also improve the safety profile and tolerability of these medications. In this review we will discuss novel treatment target agents including selective janus kinase (JAK) inhibitors, anti-interleukin (IL) (IL-12/IL-23), leukocyte trafficking/migrating inhibitors (such as sphingosine-1-phosphate receptor modulator) and other small molecules currently in development.

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“…However, the drug was efficient in several important secondary endpoints and was similarly effective as infliximab and adalimumab, underscoring its biological activity and warranting further research ( 69 – 72 ). Phase III trials in CD are still ongoing with promising results in an exploratory cohort ( 73 , 74 ).…”

Section: T Rm Cells As Potential Therapeutic Targementioning

confidence: 99%

Total Recall: Intestinal TRM Cells in Health and Disease

et al. 2021

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Tissue-resident memory T cells (TRM cells) have crucial functions in host defense in mucosal tissues. They provide local adaptive immune surveillance and allow the fast initiation of targeted adaptive immune responses in case of antigen re-exposure. Recently, an aberrant activation in the case of immunologically mediated diseases has been increasingly acknowledged. As the organ with the largest interface to the environment, the gastrointestinal tract faces billions of antigens every day. Tightly balanced processes are necessary to ensure tolerance towards non-hazardous antigens, but to set up a powerful immune response against potentially dangerous ones. In this complex nexus of immune cells and their mediators, TRM cells play a central role and have been shown to promote both physiological and pathological events. In this review, we will summarize the current knowledge on the homeostatic functions of TRM cells and delineate their implication in infection control in the gut. Moreover, we will outline their commitment in immune dysregulation in gastrointestinal chronic inflammatory conditions and shed light on TRM cells as current and potential future therapeutic targets.

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Etrolizumab for the Treatment of Ulcerative Colitis and Crohn’s Disease: An Overview of the Phase 3 Clinical Program

Cited by 66 publications

References 37 publications

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians’ Perspective

An Update for Pharmacologists on New Treatment Options for Inflammatory Bowel Disease: The Clinicians’ Perspective

Novel and Emerging Therapies for Inflammatory Bowel Disease

Total Recall: Intestinal TRM Cells in Health and Disease

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