Infliximab is the first biologic to show efficacy in two inflammatory bowel diseases ( IBD ), Crohn's Disease and ulcerative colitis.

Results from two Phase III trials presented at Digestive Disease Week 2005 showed that, among patients with moderate to severe, active ulcerative colitis who experienced an inadequate response to conventional therapy, nearly 70 percent of patients at week eight demonstrated significant improvement in their symptoms with Infliximab ( Remicade ) therapy.

Data from the ACT 1 and ACT 2 clinical trials showed Infliximab met primary and secondary endpoints of clinical response, clinical remission and mucosal healing.
Currently, there are no biologic therapies approved to treat moderate to severe ulcerative colitis, and with limited alternative treatment options, some patients face surgical removal of the colon, otherwise known as a colectomy.

The ACT 1 and ACT 2 clinical trials were conducted to evaluate the safety and efficacy of Infliximab 5 mg/kg and 10 mg/kg at weeks zero, two and six and then every eight weeks in people with active ulcerative colitis.
The primary endpoint for these trials was a clinical response at week eight, defined as a decrease from baseline in the Mayo score by greater than or equal to 30 percent and greater than or equal to three points, accompanied by a decrease in the rectal bleeding subscore of greater than or equal to one or a rectal bleeding subscore of zero or one at week eight.
Secondary endpoints also included a clinical response at week 30, clinical remission at week eight and week 30 and mucosal healing at week eight.
The serious adverse events reported in these trials were similar to those reported in previous Infliximab clinical trials.

Two randomized, placebo-controlled trials, ACT 1 and ACT 2, were designed to evaluate the safety and efficacy of Infliximab for active ulcerative colitis.
For each trial, 364 patients with active ulcerative colitis who were unresponsive to at least one standard therapy, including corticosteroids, immunosuppressants or 5-ASAs, were enrolled.
Patients in ACT 1 and ACT 2 had endoscopic evidence of moderate or severe ulcerative colitis ( total Mayo score of six to 12 ) and an endoscopy score greater than or equal to two.
For both trials, patients were randomized to receive placebo or Infliximab 5 mg/kg or 10 mg/kg.
ACT 1 patients received study agent at weeks zero, two and six and then every eight weeks through week 46 and had their last evaluation at week 54.
ACT 2 patients received study agent at weeks zero, two and six and then every eight weeks through week 22 and had their last evaluation at week 30.

In ACT 1, significantly higher proportions of patients receiving Inflixiamb 5 mg/kg ( 69 percent ) and 10 mg/kg ( 62 percent ) achieved clinical response at week eight versus placebo-treated patients ( 37 percent; P < 0.001 for both ).

In addition, at week 30, 52 percent of patients in the 5 mg/kg and 51 percent of patients in the 10 mg/kg Infliximab treatment group were in clinical response versus 30 percent of placebo-treated patients ( P < 0.001 and P=0.002, respectively ).
At week eight, 39 percent and 32 percent of patients treated with Infliximab 5 mg/kg and 10 mg/kg, respectively, were in clinical remission compared to 15 percent of placebo-treated patients ( P < 0.001 and P=0.002 ).
These differences in remission rates persisted at week 30 ( 34 percent, 5 mg/kg; 37 percent, 10 mg/kg versus 16 percent, placebo; P=0.001 and P < 0.001 ).

Mucosal healing was achieved at week eight in 62 percent and 59 percent of patients receiving Infliximab 5 and 10 mg/kg, respectively versus 34 percent of placebo-treated patients ( P < 0.001 ).

This difference in mucosal healing was maintained at week 30 ( 50 percent, 5 mg/kg; 49 percent, 10 mg/kg versus 25 percent, placebo; P < 0.001 for both ).
The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was greater in both Infliximab groups compared to the placebo group ( 24 percent, 5 mg/kg; 19 percent, 10 mg/kg; 10 percent, placebo; P=0.030 and P=0.125, respectively ).

In ACT 2, significantly higher proportions of patients receiving Infliximab 5 mg/kg ( 65 percent ) and 10 mg/kg ( 69 percent ) were in clinical response at week eight versus 29 percent who received placebo ( P < 0.001 for both ).
At week 30, 47 percent of patients receiving Inflixiamb 5 mg/kg and 60 percent receiving 10 mg/kg were in clinical response versus 26 percent of patients receiving placebo ( P < 0.001 for both ).
Clinical remission was achieved at week eight in 34 percent and 28 percent of Infliximab 5 and 10 mg/kg patients, respectively, compared to six percent of placebo-treated patients ( P < 0.001 for both ).
Differences in remission rates persisted at week 30 ( 26 percent, 5 mg/kg; 36 percent, 10 mg/kg; 11 percent, placebo; P=0.003 and P < 0.001 ).

Mucosal healing was achieved at week eight in 60 percent and 62 percent of patients receiving Infliximab 5 mg/kg and 10 mg/kg, respectively, compared to 31 percent of placebo-treated patients ( P < 0.001 for both ).
Mucosal healing at week 30 was achieved in 46 percent and 57 percent of patients receiving Infliximab 5 and 10 mg/kg, respectively, compared to 30 percent of placebo-treated patients ( P=0.009 and P < 0.001 ).
The proportion of patients who were able to discontinue corticosteroids while in clinical remission at week 30 was significantly greater in both Infliximab groups compared with the placebo group ( 18 percent, 5 mg/kg; 27 percent, 10 mg/kg; 3 percent, placebo; P=0.010 and P 0.001, respectively ).

There are reports of serious infections, including tuberculosis (TB), sepsis and pneumonia in patients receiving Infliximab. Some of these infections have been fatal.
Infliximab can lower the ability to fight infections.

There have been rare cases where people taking Infliximab have developed severe liver problems.
Blood disorders have been reported, some fatal. Nervous system disorders have also been reported.
Reports of lymphoma in patients on Infliximab and other TNF blockers are rare but occur more often than in the general population.
Serious infusion reactions have been reported with Infliximab, including hives, difficulty breathing and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common side effects: respiratory infections ( that may include sinus infections and sore throat ), coughing and stomach pain or mild reactions to infusion such as rash or itchy skin.

Source: Centocor, 2005


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