Editorial: combination immunosuppressive therapy to treat Crohn’s disease – ready for all age groups?

Regardless of its origin, and whether it truly does sit in the Hippocratic Oath, one of the central tenets of medicine is to do no harm. It is no surprise then in medicine in general that clinicians have long been ret‐ icent to treat patients with drugs with potentially serious side effects, especially in cases where the disease is not thought to be life threat‐ ening. Although our understanding of treatment goals in the manage‐ ment of Crohn's disease has evolved hugely, fear of harm is never far away, and for some patient groups there has always been a greater degree of caution. This is especially the case for the elderly patient.1 There are obvious reasons for this before we look at the data. Malignancy is more common as we age, the risk of infection is higher with immunomodulation, and ultimately the death rate is naturally higher. Paradoxically this however leads to clinicians either under‐treating dis‐ ease to avoid perceived side effects or overusing drugs and interventions that are wrongly considered to pose less of a risk, such as steroids.2 Our knowledge of the safety of drug interventions in the elderly is hampered by the lack of available trial data, as this group is often ex‐ cluded from studies. Instead, we have had to rely on post‐marketing surveillance and more latterly a wealth of ‘real world’ experience. The REACT study, which compares conventional therapy and algorithmic early combined immunosuppression in multiple practices in Belgium and Canada, is interesting for a number of reasons, not least that it does not exclude older patients, in this paper defined as those over 60 years.3 Singh et al present a post‐hoc analysis from the REACT study and observed no difference in the efficacy and safety of early combined immunosuppression with an anti‐TNF agent and immunomodulator, compared to conventional management, over a period of 2 years in older and younger patients.4 The older age group represented 15.7% of the total, which is appropriate, since 15%‐30% of the IBD popula‐ tion will consist of this age group. Before adopting early combined immunosuppression in all of our older patients, we do need to consider a few things, as the authors have alluded to in their discussion. This study was not powered to de‐ finitively demonstrate the safety of these approaches in each of the two populations. It also relied on clinical endpoints, which as we now know do not necessarily correlate with mucosal disease, and impor‐ tantly we therefore may expose some patients to unnecessary risk. However, this study does add evidence that combination im‐ munosuppressive therapy in some older patients may be safe and effective. It also reminds us that dogma and myth are increasingly unwelcome in medical practice. After all, we strive to treat the indi‐ vidual and we should be stratifying our patients using the tools and knowledge available rather than excluding populations under‐repre‐ sented in trial data. Further studies in this patient group and with different immunosup‐ pressive regimes are needed. If they give us the tools to personalise ther‐ apy further then we may demonstrate that rather than ‘doing no harm’, omission of therapy in all older patients may actually lead to the opposite.

Regardless of its origin, and whether it truly does sit in the Hippocratic Oath, one of the central tenets of medicine is to do no harm. It is no surprise then in medicine in general that clinicians have long been reticent to treat patients with drugs with potentially serious side effects, especially in cases where the disease is not thought to be life threatening. Although our understanding of treatment goals in the management of Crohn's disease has evolved hugely, fear of harm is never far away, and for some patient groups there has always been a greater degree of caution. This is especially the case for the elderly patient. 1 There are obvious reasons for this before we look at the data.
Malignancy is more common as we age, the risk of infection is higher with immunomodulation, and ultimately the death rate is naturally higher.
Paradoxically this however leads to clinicians either under-treating disease to avoid perceived side effects or overusing drugs and interventions that are wrongly considered to pose less of a risk, such as steroids. 2 Our knowledge of the safety of drug interventions in the elderly is hampered by the lack of available trial data, as this group is often excluded from studies. Instead, we have had to rely on post-marketing surveillance and more latterly a wealth of 'real world' experience. The REACT study, which compares conventional therapy and algorithmic early combined immunosuppression in multiple practices in Belgium and Canada, is interesting for a number of reasons, not least that it does not exclude older patients, in this paper defined as those over 60 years. 3 Singh et al present a post-hoc analysis from the REACT study and observed no difference in the efficacy and safety of early combined immunosuppression with an anti-TNF agent and immunomodulator, compared to conventional management, over a period of 2 years in older and younger patients. 4 The older age group represented 15.7% of the total, which is appropriate, since 15%-30% of the IBD population will consist of this age group.
Before adopting early combined immunosuppression in all of our older patients, we do need to consider a few things, as the authors have alluded to in their discussion. This study was not powered to definitively demonstrate the safety of these approaches in each of the two populations. It also relied on clinical endpoints, which as we now know do not necessarily correlate with mucosal disease, and importantly we therefore may expose some patients to unnecessary risk.
However, this study does add evidence that combination immunosuppressive therapy in some older patients may be safe and effective. It also reminds us that dogma and myth are increasingly unwelcome in medical practice. After all, we strive to treat the individual and we should be stratifying our patients using the tools and knowledge available rather than excluding populations under-represented in trial data.
Further studies in this patient group and with different immunosuppressive regimes are needed. If they give us the tools to personalise therapy further then we may demonstrate that rather than 'doing no harm', omission of therapy in all older patients may actually lead to the opposite.

ACK N OWLED G EM ENT
Declaration of personal interests: None.