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Natalizumab Maintains Remission for 2 Years in Patients With Moderately to Severely Active Crohn's Disease and in Those With Prior Infliximab Exposure: Presented at UEGW

By Chris Berrie

BERLIN, GERMANY -- October 30, 2006 -- Remission induced by natalizumab can be maintained by continuous therapy for periods more than 2 years in patients with moderate to severe Crohn's disease (CD), including those patients who previously failed therapy with infliximab.

The results from a long-term, open-label extension study following on from the Evaluation of Natalizumab as Continuous Therapy (ENACT-1) induction trial and the ENACT-2 maintenance trial were presented here on October 24^th at the United European Gastroenterology Week (UEGW) 2006.

Principal investigator Remo Panaccione, MD, associate professor of medicine and director, inflammatory bowel disease clinic, division of gastroenterology, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada.

Dr. Panaccione detailed the 3-part induction, maintenance and long-term extension series of trials with natalizumab. The ENACT-1 induction trial enrolled patients with moderate to severe active CD, defined as CD Activity Index (CDAI) score of 220 to 450. ENACT-2 then followed with the ENACT-1 subjects who had a response, defined as a 70-point or greater decrease in CDAI score from baseline score (CR-70). These subjects had completed the induction trial with mildly active CD (CDAI <220).

At the end of the ENACT-2 trial, 146 patients were in remission and enrolled in a new trial, a long-term, open-label extension study. Sixty percent, or 87 out of 146 patients, had received uninterrupted natalizumab therapy for a total of 15 months. Of these, 22 had been previously exposed to infliximab, and 11 had previously failed treatment with infliximab.

The aim of this open-label section was thus to assess the long-term safety and tolerability of natalizumab, with secondary efficacy endpoints for the proportion of patients in remission following this additional 12 months of natalizumab therapy.

A comparison of the baseline concomitant medications for ENACT-1 and this open-label extension demonstrated continued use of 5-acetylsalicylic acid (5-ASA) compounds (47% vs 44%, respectively), immunosuppressants (40% vs 38%) and antibiotics (5% vs 3%), but, as Dr. Panaccione stressed, a large reduction in the use of steroids (39% vs 6%).

For the maintenance of patients in remission from the start of this open-label extension study, there was continued maintenance of remission for the full 12 months following ENACT-2, with the full patients group (n = 87) showing a 14% decreased by the end of the 12 months. When subdivided into those previously exposed to anti-TNF (n = 22), this was slightly improved (9% drop), while for the 11 patients exposed to anti-tumor necrosis factor (anti-TNF), it was slightly worse (18% drop).

Another important aspect is the steroid-free remission over time in the natalizumab treated patients, which essentially paralleled the full data above due to the high levels of off-steroid patients (n = 80).

Thus, this total of 2 years of maintenance therapy of continued monthly infusions with natalizumab 300 mg (ENACT-2 plus open-label extension) showed the promotion of long-term remission for up to 2 years in patients with Crohn's disease, including for those previously exposed to, or who had previously failed anti-TNF therapy. Furthermore, the majority of patients maintained steroid-free remission.

Dr. Panaccione then outlined the combined ENACT-2 and open-label extension 2-year safety data (n = 87). Overall, treatment emergent adverse events were experienced by 83% of patients, with 17% being serious. Of the latter, 2% were related to the study drug.

Of the most frequently reported adverse events, nasopharyngitis and headache were the only to represent 20% or more of patients (21%, 20%, respectively). For those associated with infection, nasopharyngitis was again the most prevalent, with a frequency that was more than twice that of the other events (21%). There were also 5 serious adverse events (in 4 patients) associated with infection: abdominal abscess, neutropenic sepsis, hematoma infection, Pneumocystis carinii pneumonia and pneumonia. Finally, 6% of patients discontinued treatment due to adverse events.

In summarising these data, Dr. Panaccione also stressed that no patient on natalizumab monotherapy or with concomitant immunosuppressors and/or with steroids developed anti-natalizumab antibodies.

Thus, overall, natalizumab treatment maintained patients in remission for more than 2 years when administered as continuous therapy, with only 14% of patients showing loss of remission over this last year. As Dr. Panaccione put it, "Nearly 50% of patients who respond to natalizumab and enter remission are likely to be in remission for over 2 years on natalizumab maintenance therapy, including patients who have previously been exposed to or failed anti-TNF therapy.

This study was supported by Elan Pharmaceuticals and Biogen Idec.


[Presentation title: Natalizumab Maintains Remission for Two Years in Patients With Moderately to Severely Active Crohn's Disease and in Those With Prior Infliximab Exposure: Results From an Open-Label Extension Study. Abstract OP-G-180]

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