Treatment of Inflammatory Bowel Disease with Biologics

34

mesalazine, azathioprine, semi-elemental diet, and metronidazole [ 8 ]. After 2 years
of CD-related symptoms and stunted growth, she received open-label IFX at a dose
of 10  mg/kg for two infusions. She went into complete clinical and endoscopic
remission for 3 months however, ultimately developed a symptomatic recurrence.
This single experience led to a small open-label trial in ten patients with steroid-
unresponsive CD [ 9 ]. Eight patients received a single infusion of IFX at 10 mg/kg,
while two received 20 mg/kg to assess the safety of higher doses. Eight of the nine
patients available for follow-up responded clinically measured via decrease in the
Crohn’s Disease Activity Index (CDAI).

Clinical Efficacy

Based on the remarkable open-label experience with IFX, a multicenter randomized
controlled trial was designed to test the efficacy in moderately to severely active CD
[ 10 ]. In this trial, 108 subjects were randomized to a single infusion of placebo, IFX
at 5 mg/kg, 10 mg/kg, or 20 mg/kg. The primary end point of a 70-point reduction
in CDAI score at 4 weeks was noted in 65% of those who received IFX versus 17%
of those who received placebo (p < 0.001). More so 33% of those who received IFX
were in clinical remission versus 4% on placebo (p  <  0.005) (Fig. 3.1). No dose
response was noted, although each arm only contained 25–28 subjects limiting the

P < 0.005 P < 0.004 P < 0.17

33%

4%

Infliximab Certolizumab pegol

(PRECISE I)

Adalimumab

(CLASSIC l)

36%

Placebo

12%

22%

17%

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Induction of remission

Fig. 3.1 Induction of remission with corresponding placebo rates from seminal clinical trials for
each anti-TNF (note: trials had different inclusion criteria and end points and thus while presented
on the same chart cannot be directly compared). Infliximab outcome: week 4 remission (defined as
CDAI < 150), data pooled for doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg [ 10 ]. Adalimumab out-
come: week 4 remission (defined as CDAI < 150) following 160 mg/80 mg induction regimen [ 31 ].
Certolizumab pegol outcome: week 6 remission following 400 mg at weeks 0, 2, and 4 [ 48 ]

B. P. Va u g h n