Lengthening Adalimumab Dosing Interval in IBD patients in long term remission, the LADI study.

The inflammatory bowel diseases (IBD) are characterized by chronic inflammation
of the gastrointestinal tract. Two entities exist within IBD, namely Crohn*s
disease (CD) and ulcerative colitis (UC). These two entities differ in type,
site and extent of inflammation, disease history and extraintestinal
manifestations. Though the pathogenesis of these diseases is not fully
understood, it is known that a chronic up-regulation of the enteric mucosal
immune system, reacting to intestinal bacterial flora, plays an important role.
IBD is a common disease that affects many people, it*s incidence is similar to
diabetes mellitus type I and epilepsy. Furthermore, the incidence of IBD has
been rising over the last few decades, most likely due to a non-genetic,
life-styleassociated influence on the disease course. A particular increase in
incidence has been observed for young CD patients. For the Netherlands it is
expected that the prevalence of IBD will increase by 7% in the coming decade,
on top of approximately 80.000 Dutch patients already diagnosed with IBD.
The goal of IBD therapy is to induce rapid and sustained disease remission.
Currently, guidelines advise a step-up approach, where initial therapy consists
of the least effective and simultaneously least toxic medication. Currently,
the first tier of therapy is mesalazine is for mild-to-moderate UC and CD. If
this therapy fails, corticosteroids and immunosuppressives form the second tier
of the step-up approach. Finally, if these therapies also fail to induce or
maintain remission, anti-TNFα therapy is initiated. The use of such therapies
is currently widely established for both CD and UC patients. In the previously
reported DELTA1 cohort, 50% of the newly diagnosed IBD patients received
anti-TNFα treatment within 18 months of their diagnosis. However, this
anti-TNFα treatment is associated with high monetary costs.Specifically, in a
representative Dutch population of CD patients, anti-TNFα therapies are the
cause of 64.1% of all CD related healthcare costs, with adalimumab (ADA)
accounting for 33.9% of all CD related costs.
ADA is a fully human monoclonal IgG antibody against TNFα. It*s effectiveness
for inducing and maintaining remission in IBD patients has been studied in
several trials. The ADA dose in the maintenance phase of these studies was
40mg, administered subcutaneously every other week.
Original phase-I pharmacokinetic studies of ADA have shown that the mean
half-life after the first administration lies between 15 to 19 days. However,
after 5 months of treatment, the mean half-life increases to 21 days.
Given these pharmacokinetic data, it seems feasible to lengthen the dosing
interval of ADA from 2 to 3 weeks in IBD patients in longterm remission. If
this increased interval does not result in more disease relapse, the
cost-effectiveness of ADA would clearly improve. To our knowledge, no such
studies have been performed in IBD patients, nor in other patient populations.
As such, the aim of this study is to investigate the effects on the efficacy of
ADA maintenance therapy in IBD patients in long term remission, after
lengthening the ADA dose interval from 2 to 3 weeks.

To assess the safety of lengthening the adalimumab dosing interval from 2 to 3
weeks, in patients with Crohn*s disease or ulcerative colitis in long term (6
months) remission.

Single center, randomized controlled,open label non inferiority study with two
treatment arms

Adalimumab every 3 weeks

In this study patients will have to visit the site more frequently and
additional blood samples will be drawn each visit.
The work-up in case of suspected relapse is not different from daily practice,
and does not result in additional burden.