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complications (HR 0.74, 95% CI 0.62–0.89) and surgeries (HR 0.68, 95% CI 0.49–
0.95) and the combined outcome of hospitalizations, complications, and surgeries
(HR 0.74, 95% CI 0.62–0.87). Within this trial, an important point to be noted is that
they followed a treat-to-target algorithm where adjustments in therapy were made if
patients had not achieved clinical remission at 3–6-month intervals. This approach
may have factored into the overall impact of ECI and suggests that the timing of
concomitant immunosuppressive therapy and the manner in which we monitor and
adjust dosing are equally important.
In aggregate, direct comparative effectiveness studies demonstrate that the con-
comitant use of an immunosuppressive agent improves treatment outcomes and
reduces disease-related complications in IBD. The optimal approach to using con-
comitant immunosuppressive therapy with TNF-antagonists is early in the disease
course with frequent monitoring and adjustments in dosing or therapies when clini-
cal remission has not been achieved. The ideal choice of which immunosuppressive
agent to use appears to be azathioprine (6-mercaptupurine can likely be used as
well) based on efficacy, but providers will need to take into consideration differ-
ences in trial characteristics and variations in outcomes across trials. Consideration
for immunosuppressive safety will therefore likely drive the decision as to which
immunosuppressive agent is chosen on an individualized basis.
Safety
When taking into consideration the optimal use of a therapeutic agent or the combi-
nation of therapies, we must take into consideration the impact safety will have on
patient outcomes and adherence. Specifically, we must understand the safety profile
when immunosuppressive agents are added or continued alongside biologic agents
and the populations at greater risk for adverse events when using concomitant
immunosuppressive therapy. Two of the most notable safety concerns with con-
comitant immunosuppressive therapy are serious infections and malignancy.
Serious Infections
Treatment-related serious infections can be broadly categorized as those resulting in
the interruption or discontinuation of therapy, hospitalization, or death. Although
randomized controlled trials have not demonstrated an increased risk for serious
infections with the addition of immunosuppressive agents to biologics, population-
based studies have observed an increased incremental risk, with the majority of this
risk being attributed to the concomitant use of steroids [ 23 – 27 ]. Any prednisone use
can increase the risk of serious infections, but doses higher than 20 mg of prednisone
for 2 or more weeks are associated with the most significant risk for serious infec-
tions, and this risk persists for up to 90 days after exposure [ 28 , 29 ]. This risk can be
further augmented in certain patients who are already at an increased baseline risk
for treatment-related serious infections. Two subgroups of particular importance are
P.S. Dulai and C.A. Siegel