Monitoring vedolizumab and ustekinumab drug levels in patients with inflammatory bowel disease: hype or hope?

Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

“…A similar exposure-efficacy relationship has been observed for ustekinumab: early TLs (week 4 and 8) have been associated with clinical remission [109,110], decrease of faecal calprotectin [111] and biochemical remission [112], while TLs during maintenance have been correlated with clinical remission [109,110], endoscopic response [111,113] and need for optimization [114]. In a recent review, Alsoud et al [127] proposed target TLs for vedolizumab and ustekinumab. During induction, TLs >20 μg/mL at week 6 and >14 μg/mL at week 14 have been suggested for vedolizumab, whereas for ustekinumab >14 μg/mL and >4 μg/mL at weeks 4 and 8, respectively; during maintenance phase, TLs >12 μg/mL for vedolizumab and >2.5 μg/mL for ustekinumab have been proposed [127].…”

“…In a recent review, Alsoud et al [127] proposed target TLs for vedolizumab and ustekinumab. During induction, TLs >20 μg/mL at week 6 and >14 μg/mL at week 14 have been suggested for vedolizumab, whereas for ustekinumab >14 μg/mL and >4 μg/mL at weeks 4 and 8, respectively; during maintenance phase, TLs >12 μg/mL for vedolizumab and >2.5 μg/mL for ustekinumab have been proposed [127].…”

Novel trends with biologics in inflammatory bowel disease: sequential and combined approaches

“… 74 , 99 In case of primary failure, evidence on the appropriateness of TDM is less convincing, and out-of-class swap is usually preferred, 73 even though it has been observed that reactive TDM might be beneficial in some cases. 100 Fewer data on reactive TDM with non-anti-TNFα agents exist, and it is not recommended in routine clinical practice; however, evidence from post hoc analysis of pivotal trials and observational studies have demonstrated that a dose-response correlation exists for these molecules 101 ; therefore, it might be possible that reactive TDM could help discriminate patients who might benefit from dose-escalation from those who need out-of-class swap. Indeed, being able to identify patients with pharmacokinetic failure would be extremely useful; inadequate drug levels only account for certain cases of treatment inefficacy, and patients can also become ‘insensitive’ to the drug’s mechanism of action.…”

T-Cell Adhesion in Healthy and Inflamed Skin

“…Therapies targeting adhesion pathways are currently approved for treatment of autoimmune and inflammatory diseases including, multiple sclerosis, Crohn's disease and ulcerative colitis (Alsoud et al 2020;Ley et al 2016). Predominantly, these approaches rely on monoclonal antibody based blockade of integrin function, although a small molecule LFA-1 antagonist, lifitegrast, is currently approved for dry eye disease (Haber et al 2019).…”

“…Predominantly, these approaches rely on a mAb-based blockade of integrin function, although a small molecule LFA-1 antagonist, lifitegrast, is currently approved for dry eye disease ( Haber et al., 2019 ). Vedolizumab, which possesses a safe and effective track record in the treatment of Crohn’s disease and UC ( Alsoud et al., 2020 ; Feagan et al., 2013 ), provides an illustrative example for the successful development of tissue-specific adhesion‒based therapeutics. Vedolizumab binds to a conformational epitope unique to the heterodimerization of human α 4 and β 7 integrins.…”