CENTOCOR
Chimeric monoclonal antibody approved for the treatment of ulcerative colitis and maintenance of clinical remission
Infliximab was approved on October 13, 2006, for the reduction of signs and symptoms, induction and maintenance of clinical
remission and mucosal healing, and elimination of corticosteroid use in patients with moderately to severely active ulcerative
colitis who have had an inadequate response to conventional therapy. This monoclonal antibody binds to tumor necrosis factor
(TNF)-alpha, inhibiting its biological activity.
Efficacy. The efficacy of infliximab was evaluated in 2 studies (UC I and UC II) that enrolled a total of 728 patients with moderately
to severely active ulcerative colitis (Mayo score, 6–12 [possible range, 0–12]; endoscopy subscore ≥2) who had not responded
adequately to conventional oral therapies, including oral corticosteroids, 6-mercaptopurine, and azathioprine in UC I and
these medications and/or aminosalicylates in UC II. Patients were randomized to receive either placebo or 5 or 10 mg of infliximab
at Weeks 0, 2, and 6 and every 8 weeks thereafter through Week 46 in UC I and through Week 22 in UC II. Clinical response
was defined as a Mayo score decrease from baseline ≥30% and ≥3 points, as well as a decrease in the rectal bleeding subscore
of ≥1 or a rectal bleeding subscore of 0 or 1. Both studies demonstrated statistically significant (P<.01 for all) improvement among infliximab-treated patients versus placebo-treated patients in the parameters of clinical
response, sustained response, clinical remission, sustained remission, and mucosal healing. In UC I, patients treated with
infliximab 5 or 10 mg achieved clinical response rates of 69% and 62% at Week 8, 52% and 51% at Week 30, and 45% and 44% at
Week 54, respectively, versus 37% at Week 8, 30% at Week 30, and 20% at Week 54 among patients who received placebo. Clinical
remission (Mayo score ≤2 points and no individual subscore >1) was sustained through Week 54 in 20% of both the infliximab
5- and 10-mg groups and in 7% of the placebo group. In UC II, patients treated with infliximab 5 or 10 mg achieved clinical
response rates of 65% and 69% at Week 8 and 47% and 60% at Week 30, respectively, versus 29% at Week 8 and 26% at Week 30
among patients who received placebo. Clinical remission was sustained through Week 30 in 15% of patients treated with infliximab
5 mg, 23% of patients treated with infliximab 10 mg, and 6% of patients who received placebo. Safety. Patients treated with infliximab have an increased risk of serious infections, including bacterial sepsis, tuberculosis,
and invasive fungal and other opportunistic infections, the progression of which could lead to hospitalization or death. Treatment
of latent tuberculosis should be initiated before infliximab therapy, and infliximab should not be administered to patients
with clinically important, active infections. The risk of serious infection is increased when infliximab is co-administered
with etanercept and anakinra. Infliximab doses >5 mg/kg should not be administered to patients who have moderate-to-severe
heart failure. Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis, have been reported
rarely among patients receiving infliximab. Leukopenia, neutropenia, thrombocytopenia, and pancytopenia also have been reported
in infliximab-treated patients; some cases have been fatal. Infusion-related reactions, including flu-like symptoms, headache,
dyspnea, hypotension, transient fever, chills, gastrointestinal symptoms, and skin rashes, are common.
Dosing. The recommended dose of infliximab is 5 mg/kg at 0, 2, and 6 weeks for induction, followed by 5 mg/kg every 8 weeks for maintenance.
Infusion should begin within 3 hours of solution preparation, and the solution must be administered over a period of ≥2 hours.
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