Biologic and other novel
therapies targeted to specific pathogenic processes offer the potential for improved treatment outcomes in patients with
Crohn's disease and alteration of the course of the disease.
Therapies targeted to
tumor necrosis factor alpha (
TNF-alpha) include anti-
TNF-alpha monoclonal antibodies (
infliximab and
CDP-571), TNF-binding neutralizing fusion
proteins (
etanercept), and
TNF-alpha production inhibitors (
thalidomide). In placebo-controlled trials,
infliximab has rapidly induced clinical response and remission in patients with moderately to severely active
Crohn's disease refractory to conventional
therapy and patients with fistulizing
Crohn's disease, with minimal toxicity;
retreatment with
infliximab in patients who experienced an initial response maintained their clinical improvement. Clinical experience suggests that
infliximab may also be effective when administered as
corticosteroid-sparing
therapy.
Infliximab is the only anti-
TNF-alpha therapy currently available in clinical practice for the treatment of active
Crohn's disease. Controlled trials of the investigational anti-
TNF-alpha agent
CDP-571 show benefit for induction of clinical improvement and
steroid-sparing, but further investigation is needed. A pilot study of
etanercept suggested a beneficial effect, but its efficacy was not confirmed in a controlled trial. In open-label trials,
thalidomide has demonstrated efficacy in patients with refractory
Crohn's disease; however, the therapeutic potential of
thalidomide may be severely limited by the high incidence of
drug-induced side effects. Other novel agents, including anti-alpha4
integrin antibodies,
interleukin (IL)-10 and
IL-11, and the
immunomodulators tacrolimus and
mycophenolate mofetil have been evaluated as treatment in patients with severely active or fistulizing
Crohn's disease in open-label and controlled trials, with varied results reported to date. The development of these new
therapies is an exciting advance that promises to improve the management of
Crohn's disease and expand current knowledge of underlying pathophysiologic mechanisms.