39scored using the CDEIS, and while the initial assessment was study site specific, the
final assessment was performed by a blinded central reviewer. In the intention to treat
analysis, 27% of subjects in the ADA group achieved mucosal healing at week 12
versus 13% with placebo (p < 0.056). At week 52, the mucosal healing rate was 24%
for those on ADA, while none of the subjects in the placebo group achieved mucosal
healing (p < 0.001). Additionally, using clinical data from EXTEND, ADA was shown
to improve a composite outcome including clinical remission and mucosal healing
[ 44 ]. Similar to mucosal healing rates, no significant difference was noted at week 12,
while 19% of those on ADA achieved deep remission at week 52 versus 0% on pla-
cebo (p < 0.001).
Fistula Healing
In the CLASSIC I trial, the rates of fistula improvement and remission for ADA
and placebo groups were not significantly different, although only 11% of ran-
domized patients had draining enterocutaneous fistulas [ 31 ]. Among those with
fistulas at baseline, more patients in CHARM experience complete fistula clo-
sure at week 56 on ADA therapy (33%) versus placebo (13%) (p < 0.016) [ 33 ].
An open-label Canadian trial, Adalimumab in Canadian Subjects with Moderate
to Severe Crohn’s Disease (ACCESS), found that fistula healing rates at week
24 were as high as 60% for anti-TNF-naïve subjects and 28% for those previ-
ously treated with IFX [ 40 ]. In a randomized controlled trial of ADA plus cip-
rofloxacin versus ADA alone, those with ADA plus ciprofloxacin had a
significantly higher reduction in fistula at 12 weeks versus ADA alone (71%
versus 47%, p < 0.047) [ 45 ]. Complete fistula close was noted in 33% of ADA
subjects at week 12 versus 65% of ADA plus ciprofloxacin (p < 0.009).
Certolizumab Pegol
Certolizumab pegol (CZP) is a humanized fragment of a monoclonal antibody that
is a strong neutralizer of TNF but lacks the typical Fc portion of the parent IgG4
antibody and instead contains two molecules of polyethylene glycol [ 46 ]. The
PEGylation of the antibody increases the plasma half-life and also prevents passage
across the placenta during pregnancy [ 47 ].
Clinical Efficacy
The early randomized phase II placebo-controlled trial for CZP consisted of 92
adult subjects with moderate to severe CD who were randomized to CZP at varying
doses and placebo [ 46 ]. The primary efficacy of clinical response at week 4 was
similar for the three CZP treatment groups (5 mg/kg, 10 mg/kg, and 20 mg/kg) and
3 Antitumor Necrosis Factor Agents in Crohn’s Disease