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Future Considerations
We have summarized the current evidence available to guide concomitant
immunosuppressive use with TNF-antagonists, but several questions remain.
With the advent of immune pathway-specific biologics, consideration can be
given to using a second biologic in place of the immunosuppressive agent to
achieve optimal clinical outcomes [ 72 ]. Another important concept under eval-
uation is the personalization of treatment decisions when using concomitant
immunosuppressive agents based on an individual patient’s risk profile for
developing complications. As not all IBD patients will progress on to disease-
related complications or adverse events, the blanket use of concomitant immu-
nosuppressive therapy may be unnecessary in certain subgroups. A web-based
program linking a video decision aid about the benefits and risks of Crohn’s
therapy to a personalized decision-making tool which presents a prediction of
disease severity based on patient demographics, disease characteristics, genetic
variables, and serological markers has now been developed. Providers are able
to input these data in the program which then graphically depict a patient’s
individual risk for disease-related complications. This web-based patient com-
munication tool has now been validated in both adult and pediatric Crohn’s
disease patients, and the impact of this tool on provider and patient decisions
is currently under investigation [ 73 , 74 ].
Summary
In summary, the combination of TNF-antagonists with immunosuppressive
agents is clearly superior to TNF-antagonist monotherapy for improving treat-
ment response and long-term outcomes. The optimal timing of using combined
immunosuppressive therapy is early in the disease course prior to the develop-
ment of disease-related complications. When using concomitant immunosup-
pressive therapy, opportunities exist to personalize treatment decisions and
mitigate treatment-related risks through appropriate disease and drug monitor-
ing. In a subset of patients, TNF-antagonist monotherapy may be appropriate,
but providers will need to approach this decision with caution to ensure loss of
response and immunogenicity do not occur. As new biologics and small mole-
cules are developed, comparative effectiveness studies will be needed to under-
stand if these new agents should be used as monotherapy or in combination with
currently available biologics or immunosuppressives. When guiding patients
through this decision-making process, a combined approach of optimizing effi-
cacy and minimizing safety concerns should be taken through a personalized
approach. We have provided a summary outline for consideration, but the deci-
sion will ultimately need to be personalized based on patient and provider
preferences.
P.S. Dulai and C.A. Siegel