Tailoring treatment withdrawal in inflammatory bowel disease
Patients may not relapse over mid-term and those who have relapsed may have benefited from a drug-free period before being treated again.
There is currently no cure for inflammatory bowel disease. Most recent treatments and treatment strategies allow for healing intestinal lesions and maintaining steroid-free remission in a subset of patients. These patients and their doctors often ask themselves whether the treatment could be withdrawn.
Several studies in both Crohn’s disease and ulcerative colitis have demonstrated a risk of relapse, which varies between 20 and 50% at 1 year and between 50 and 80% beyond 5 years. These numbers clearly highlight that stopping therapy should not be a systematically proposed strategy in those remitting patients. Nevertheless, they also indicate that a minority of patients may not relapse over mid-term and that those who have relapsed may have benefited from a drug-free period before being treated again for a new cycle of treatment.
In this context, it would be good to optimally select patients who can be candidates for a successful treatment withdrawal. The criteria impacting this decision are as follows: the risk of relapse (linked to factors like mucosal healing and biomarkers), the consequence of a potential relapse, the tolerance and potential side effects of therapy, patients’ priorities and preferences, and the costs. Integration of these parameters allows for the proposal of a decisional algorithm that may help the patients and doctors to make an appropriate decision for their individual case.
The cure for a disease is logically considered as a main situation where a treatment withdrawal can be decided. However, there is currently no cure for inflammatory bowel disease (IBD). In our current conception, those are multifactorial polygenic diseases (1). Therefore, a cure is highly unlikely. What we could imagine is to be able to sufficiently modify the environment to be able to stop the ongoing immuno-inflammatory process (2).
There are two limitations to this possibility: first, the self-perpetuation of inflammation would be installed and not be possible to stop even retrieving environmental triggers, and second, the cumulated tissue damage would generate symptoms. This second point should not be an obstacle to treatment withdrawal but would rather require complementary symptomatic treatments. Beyond this, a treatment withdrawal would also make sense when the benefit of the treatment is lower than its risk and/or cost. Most often, it is considered that cost here is a political health care system or a pragmatic insurance company decision that cannot be made at the level of individual patients.
The situation where it could be decided on an individual patient basis is when the patient is not covered for his/her medical fees and has to decide himself or herself how to spend money, including for health care. This situation is very rare in western Europe. Nevertheless, public or private health institutions have important decision to make in this field. For them, the benefit/cost ratio is certainly relevant and has to be taken into account.
For the physician, it is thus usually the benefit/risk ratio that is dominant. Assessing this is not an easy task as the physician thus needs to integrate and compute at the same time the risk of ongoing drug therapy and the benefit of this therapy. Furthermore, the risk linked to treatment withdrawal is not limited to the risk of relapse. We also have to consider the probability of rapidly recovering remission after retreatment, and if the response to retreatment was not appropriate, the consequences of the disease flare, including the risk of surgical resection. It is even more complicated as the physician should also integrate the patient’s preferences and priorities. Indeed, the acceptance of the risk of side effects and the risk of disease progression may vary from patient to patient.
The aims of this review article are to illustrate the most important factors to consider when contemplating treatment withdrawal in IBD and to propose a way to integrate these various factors. The benefit/risk and benefit/cost ratios of mesalazine has been recently reviewed and probably remains positive over time (3). Therefore, we will focus on biologic and immunomodulator withdrawal. As far as biologic therapy is concerned, there are currently essential data on anti-tumor necrosis factor (anti-TNF) and concerning an immunomodulator, essentially purines.