Treatment of Inflammatory Bowel Disease with Biologics

106

therapy as a general rule of thumb appears to be most appropriate for IBD patients with

extensive disease or those at risk for disease-related complications (i.e., steroid depen-

dent or refractory) [ 6 , 18 , 57 ]. Among these individuals, the decision to personalize the

use of concomitant immunosuppressive therapy can be made through an assessment of

safety and long-term risks. In young males at risk for HSTCL, short-term use of con-

comitant thiopurines, TNF-antagonist monotherapy, or the use of methotrexate as the

concomitant immunosuppressive agent may be most appropriate given the fatal nature

of this lymphoma. In the elderly or individuals at risk for lymphoma with extended use

of thiopurines, TNF-antagonist monotherapy, discontinuation of the thiopurine after

1–2 years of use, or switching to methotrexate may be reasonable options. The risk of

malignancy in patients using thiopurines rises exponentially after 2 years of use [ 50 ,

58 ], and the risk of malignancy in patients discontinuing thiopurines appears to return

to the baseline risk seen in patients without prior exposure [ 58 ]. Thus, withdrawing the

thiopurine after 2 years of use can be considered, particularly in patients at low risk for

relapse upon immunosuppressive withdrawal [ 18 ] (Table 7.3). This approach is how-

ever associated with reductions in TNF-antagonist drug concentrations and the devel-

opment of antidrug antibodies, so patients should be followed up closely to optimize

TNF- antagonist dosing as needed [ 59 – 62 ].

In individuals at an increased risk for serious infections or other thiopurine- related

adverse events, opportunities to optimize the use of concomitant immunosuppressive

Steroid dependent/refractory, or

severe IBD (with or without IBD

related complications)?

YES NO

COMBO

Increased

Risk for AE?

NO YES

Lymphoma? Infection orother AEs?

Age

Male ≤ 25

years ≥^65 years

AZA/6MP Combo with

early IS withdrawal or

switch to MTX;

or Anti-TNF Mono

Ant-TNF Mono;

short-term

Thiopurine

Combo or

MTX Combo

Modify Risk

Factors

AZA/6MP Combo with

Metabolite monitoring;

or Anti-TNF Mono

AZA/6MP
Combo

Increased

Risk for AE?

NO YES

AZA/6MP

Combo

Anti-TNF

Mono

Failing Anti-

TNF Mono

Add AZA/6MP

Combo

Anti-TNF Monotherapy or Combo Therapy

Fig. 7.1 Considerations when determining whether to use a concomitant immunosuppressive

agent with TNF-antagonists. IBD inflammatory bowel disease, AE adverse event, AZA azathio-

prine, 6MP 6-mercaptopurine, anti-TNF tumor necrosis factor antagonist, MTX methotrexate, IS

immunosuppressive

P.S. Dulai and C.A. Siegel