293consequences of which are presently unknown. This could have implications on
vaccination against enteric infections such as rotavirus (an oral vaccine) but possi-
bly not parenteral agents commonly administered in the first year of life. No
evidence- based recommendations can be made at the present time, and any inten-
tional use in pregnancy would need to be discussed on a case-by-case basis. Data on
vedolizumab use in the paediatric age group are limited to retrospective observa-
tional data in largely TNF-exposed patients, suggesting a remission rate of 100% at
14 weeks in three patients with UC, an improvement to the comparative 44%
reported in nine Crohn’s patients [ 64 ]. A phase III study of vedolizumab of patients
15 years and older is currently ongoing (ClinicalTrials.gov:NCT02039505), and a
phase III PK/PD paediatric trial is about to start.
Therapeutic Drug Monitoring
The quantification of drug levels and anti-drug antibodies has garnered appropriate
attention with supportive evidence for correlation between trough levels and thera-
peutic outcomes [ 65 ]. In the GEMINI studies, a positive correlation was noted
between VDZ levels and efficacy [ 42 , 43 ]. Dosing frequency (q4 or q8 weekly) had
no effect on drug levels with both leading to α 4 β7 saturation in ≥95% serum lym-
phocytes. Anti-vedolizumab antibodies were noted in 1–4.1% of patients in GEMINI
I and II of which 0.4–1% were persistently positive and concomitant immunosup-
pression was associated with reduced immunogenicity consistent with observations
with anti-TNF therapy [ 65 ]. No difference in efficacy was noted between mono-
therapy and combination with immunosuppressive therapy in the GEMINI trials.
They were, however, not powered for detection. That said, with much of the present
appeal for vedolizumab is in its gut specificity and consequently its safety profile,
monotherapy may find more favour in the light of present evidence. The availability
of vedolizumab trough and antibody testing in the USA since May 2016 and data on
its impact on clinical endpoints and decision making are eagerly awaited.
Head-to-head comparisons between vedolizumab and other biological agents
and its role in special situations discussed above are now needed to better position
it in current treatment paradigms of active IBD.
AMG 181
AMG 181 is a fully human (IgG2) α 4 β7 integrin antibody that, like vedolizumab,
specifically inhibits binding to MAdCAM-1 but not VCAM-1. AMG 181 has
showed in vitro pharmacology and pharmacokinetic and pharmacodynamic charac-
teristics in cynomolgus monkeys rendering the compound suitable for evaluation in
humans [ 66 ]. Results of phase I studies are not published yet.
16 Anti-integrin Agents in IBD: Efficacy and Risk of Complications