Phase 3 infliximab data show excellent initial responses

September 1, 2006

Results from one year of follow-up in a phase 3 trial investigating infliximab (Remicade, Centocor) for the treatment of moderate-to-severe psoriasis demonstrate that the dramatic responses, achieved rapidly after induction therapy, are sustained with maintenance therapy in the majority of patients and without the emergence of new safety concerns, reported Alan Menter, M.D., at the American Academy of Dermatology's Academy '06.

Results from one year of follow-up in a phase 3 trial investigating infliximab (Remicade, Centocor) for the treatment of moderate-to-severe psoriasis demonstrate that the dramatic responses, achieved rapidly after induction therapy, are sustained with maintenance therapy in the majority of patients and without the emergence of new safety concerns, reported Alan Menter, M.D., at the American Academy of Dermatology's Academy '06.

Known as the Evaluation of Infliximab for Psoriasis (Remicade) Efficacy and Safety Study II (EXPRESS II), the randomized, double-blind, phase 3 trial entered 835 patients at 63 sites in the United States, Canada and Europe. Participants were assigned into one of three treatment arms to receive placebo or infliximab 3 mg/kg or 5 mg/kg administered in an induction regimen of three infusions at weeks zero, two and six. At week 14, the patients in the infliximab groups were rerandomized to receive maintenance treatment with their original dose of infliximab either every eight weeks or "as needed." Placebo patients were crossed over at week 16 to receive an induction regimen with infliximab 5 mg/kg and then to continue with routine maintenance injections every eight weeks.

Within each infliximab dosage group, the rate of sustained improvement was greater among patients receiving routine, every-eight-weeks maintenance therapy relative to those being treated in the "prn" arm, with optimal results being achieved with scheduled maintenance therapy using the 5 mg/kg dose. Improvements in quality of life, as measured by the Dermatology Life Quality Index, were consistent with the benefits measured in the PASI score.

"Psoriasis cannot be considered a 12-week disease, and, thus, we need to do all possible so as not to allow affected patients to flare after an initial good response. However, experience accumulated over the past few years using infliximab in the treatment of psoriatic arthritis indicates that the every-eight-week schedule for reinfusion is more of a general guideline than a rule.

"Depending on the individual patient's situation, retreatment frequency, as well as dose, may need to be increased or decreased for optimal effect," Dr. Menter notes.

"Clinical trial experience has also revealed there is a small subgroup of patients who appear to be rapid metabolizers of infliximab. Those individuals have no detectable blood levels two weeks after infusion and no significant neutralizing antibody response. This phenomenon is the subject of ongoing study."

FAVORABLE SAFETY

Infliximab was generally well-tolerated in EXPRESS II without new safety issues arising during the maintenance treatment period. Through week 14, adverse events occurred in about two-thirds of patients in both infliximab groups compared with slightly more than half of the patients in the placebo group. Rates of serious adverse events were 1 percent and 3 percent in the infliximab 3 mg/kg and 5 mg/kg groups, respectively, and 2 percent for placebo.

Laboratory abnormalities were generally uncommon, but significant liver function test (alanine aminotransferase) elevations were noted in approximately 5 percent of patients through week 50.

"It is unsure whether psoriasis patients may be more predisposed to develop liver function abnormalities with infliximab than rheumatoid arthritis (RA) patients," Dr. Menter says. "We know that rates of liver function test elevations are higher in psoriasis patients treated with methotrexate as monotherapy compared with RA patients. Obviously, it will be important to monitor liver function in patients who may already be at increased risk for problems."