41primary outcome of clinical remission at week 6 (32% and 25% for CZP and
placebo, respectively, p < 0.174) [ 50 ]. However as with other CZP trials, when
only looking at those with an elevated CRP (>5 mg/L), significant differences
between CZP and placebo were noted. In PRECISE 1 and 2, the rates of antidrug
antibody formation were 8 and 9%, respectively [ 48 , 49 ].
PRECISE 3, an open-label extension including participants from PRECISE 1
and 2, demonstrated efficacy for CZP over a longer period as well as established that
continuous therapy was superior to interrupted therapy [ 51 ]. Those in the placebo
arm of PRECISE 1 or 2 were given the option for open-label CZP at the end of the
study and then followed for an additional 54 weeks. Similarly to other anti-TNFs,
those on continuous CZP had a response rate of 40% versus 27% for those who
received interrupted CZP. Twenty percent of those who started the open-label exten-
sion completed the 7-year follow-up. At 7 years, a higher proportion of those who
started the extension study in remission remained in remission versus those not in
remission at the start of the extension, indicating that those who achieved remission
on CZP could maintain a long-term remission [ 52 ].
Mucosal Healing
PRECISE 1 and 2 did not have mucosal healing end points. The Endoscopic
Mucosal Improvement in Patients with Active Crohn’s Disease Treated with CZP
(MUSIC) trial was an open-label single-arm study to assess the efficacy of CZP
for mucosal healing [ 53 ]. Subjects were given CZP 400 mg at weeks 0, 2, 4, and
8 then every 4 weeks, and the primary outcome was endoscopic improvement
assessed via CEDIS at week 10 compared to baseline; the main secondary out-
come was endoscopic improvement at week 54. Of the 89 subjects enrolled, 88%
had a week 10 colonoscopy revealing a significant decrease in mucosal lesions
(mean CDEIS decrease of 5.7 from baseline, 95% CI 5.3, 7.6, p < 0.001) with 4%
(95% CI 1, 11) being in mucosal healing [ 53 ]. At week 54, the mucosal healing
rates increased to 13% (95% CI 6, 25). Although this study lacked a control
group, a significant decrease in mucosal lesions was noted on CZP that persisted
through 1 year.
Fistula Healing
In PRECISE 1, the rate of fistula healing was similar in the CZP and placebo arms
(30% and 31%, respectively) [ 48 ]. In PRECISE 2, only 14% of patients had drain-
ing fistulas on inclusion, and thus no conclusions could be drawn for fistula closure
[ 49 ]. A small Swiss multicenter cohort questionnaire-based study, reflecting the
real-world experience with CZP, noted that 73% (8/11 subjects) had a 50% decrease
in the number of draining perianal fistulas at 6 weeks [ 54 ].
3 Antitumor Necrosis Factor Agents in Crohn’s Disease