Lots of young people work their way through various medications during their IBD course – either because they have no effect, they lose effect or they are not tolerated due to unwanted side effects. Any new drug that is safe and effective in the treatment of Crohn’s is therefore welcome, especially one which can be taken by mouth and does not require an injection or infusion.
This is the report from the phase II stage of a trial of a drug called laquinimod – a new oral medicine which inhibits cells called antigen presenting cells and T-cells which are involved in promoting inflammation. A phase II trial tests a drug in a moderate number of people to see if it is effective and further tests safety (already tested in a small number of people in phase I trials).
180 patients (adults aged 18-67 years old) with moderate-severe Crohn’s disease were recruited from 37 different centres across 9 countries and randomly assigned to take laquinimod (at one of four different doses) or a placebo (control/dummy drug which has no effect but appears identical to the test drug) for 8 weeks, then followed up for another 4 weeks.
The two lower doses of laquinimod were most effective at achieving either remission or a response at 8 weeks compared to the higher doses and placebo (48% in the lowest dose group compared with 15.9% in the placebo group). Patients on these lower doses entered remission earlier than those on placebo; the benefit of the lowest dose laquinimod was noticeable by week 2 of treatment and consistent through to week 8 and at the additional 4 weeks of follow-up.
The overall incidence of unwanted side effects was similar in the laquinimod group to the placebo group; most were mild to moderate severity. Patients who received the highest dose of laquinimod were most likely to stop taking the drug due to side effects (most frequently exacerbation of their Crohn’s). The commonest unwanted effect was headache, especially in the high dose group.
What does this mean?
Laquinimod was safe and generally well tolerated in this trial. When used at the lowest dose in this study, it had the most beneficial effect on response and remission. Phase III trials (the next stage in larger groups of people) are now underway using the drug at the low dose and an even lower dose, to confirm its effectiveness and safety profile. If it is shown to be effective, it could eventually provide a novel treatment option that can be taken by mouth.