Treatment of Inflammatory Bowel Disease with Biologics

38

of the entire CHARM cohort (including those who received open-label ADA) found
that continuous ADA was a more effective treatment strategy versus induction dos-
ing followed by retreatment for clinical flare [ 34 ].
Long-term follow-up studies of ADA from CHARM and the open-label exten-
sion, Additional Long-Term Dosing With HUMIRA to Evaluate Sustained
Remission and Efficacy in CD (ADHERE), demonstrated improved rates of steroid-
free remission at 2, 3, and 4 years compared to placebo [ 35 – 37 ]. Additionally mul-
tiple analyses from these large randomized controlled trials demonstrate that ADA
is effective at improving patient-reported outcomes for CD [ 38 – 40 ], reducing costs
[ 38 , 41 ], and reducing all-cause hospitalizations and surgery [ 42 ].

Mucosal Healing

The ability for ADA to induce and maintain mucosal healing was assessed in the
EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic
Healing) trial [ 43 ]. This study is notable in that it was the first prospective, random-
ized, placebo-controlled study with mucosal healing as an end point. All subjects were
given open-label ADA for induction (160 mg at week 0 and 80 mg at week 2), and
those with a clinical response (decrease in CDAI by at least 70 from baseline) were
randomized to maintenance with ADA 40 mg every other week or placebo. Subjects
who flared or were nonresponders were given open-label ADA. Ileocolonoscopy was

P < 0.003 P < 0.001P < 0.001

39%

21%

Infliximab

(ACCENT I)

Certolizumab pegol

(PRECISE 2)

Adalimumab

(CHARM)

40%

Placebo

17%

48%

28%

100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0%

Maintenance of remission

Fig. 3.2 Maintenance 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 30 clinical remission
dosed at 5 mg/kg [ 12 ]. Adalimumab outcome: week 26 remission dosed at 40 mg every other week
[ 33 ]. Certolizumab pegol outcome: week 26 clinical remission dosed at 100 mg every 4 weeks [ 49 ]

B. P. Va u g h n