Treatment of Inflammatory Bowel Disease with Biologics

107

therapy can be taken through modifying risk factors and thiopurine metabolite assess-
ments [ 63 – 67 ] (Fig. 7.2). The traditional therapeutic efficacy window for thiopurine
monotherapy is a thioguanine (TGN) level of between 235  pmol/8  ×  10^8 and
450 pmol/8 × 10^8 RBCs. When using thiopurines as concomitant immunosuppressive
agents, however, the therapeutic efficacy window for reducing antidrug antibodies
may be lower (125 pmol/8 × 10^8 RBCs) [ 68 – 70 ]. A crude measure of TGN levels is
peripheral RBC mean corpuscular volume (MCV) [ 71 ]. In a post hoc analysis of
SONIC, patients who had achieved a mean increase in MCV of 7 were more likely to
be in steroid-free remission, achieve mucosal healing, and obtain an infliximab con-
centration of >3, as compared to those who hadn’t achieved a delta change in MCV of
7 or more. As patients will need regular blood test monitoring while on thiopurines,
following peripheral MCV measurements could serve as a reliable interim surrogate
for achieving optimal thiopurine concentrations.

Table 7.3 Factors associated
with disease relapse after
stopping an
immunosuppressive agent

Extensive disease or elevated inflammatory markers

(CRP, platelet count, white blood count)

Evidence of mucosal activity on endoscopy

Short duration in remission prior to stopping

Short duration of steroid-free remission

Thiopruine use

Viral testing and

Vaccination

Hepatitis B

Vaccinate if no immunity, consider

treatment if positive/active infection

Varicella Zoster

Vaccination if negative serology

Epstein Barr Virus

Consider avoidance of thiopurineif IgG EBV

negative or acute infection given risk of

EBV related lymphoma

Pneumococcal and Influenza vaccination

Avoid live vaccines while on thiopurines

TPMT testing

Complete Deficiency
Avoid thiopurines
Heterozygotes
Start at lower dose (50%)
Ultrahigh TPMT or hypermethylation
Low probability for efficacy and
increased risk of liver toxicity
Metabolite
Monitoring

4-6 weeks after initiation

or dose adjustment

TGN : 125 pmol/8×1 08 to

MMP > 5,700 pmol/8×10 450 pmol/8×1 08 RBCs

8

Increased risk for

hepatotoxicity – Split

dosing to reduce

MMP concentrations

Optimal dosing achieved for

Combo therapy; if TGN < 12 5

then increase dose

TGN > 400 pmol/8×1 08

Increased risk for leukopenia – if

inactive disease then reduce

dose, if active disease then

thiopruine refractory and stop

Fig. 7.2 Clinical algorithm to monitor concomitant immunosuppressive use and optimize effectiveness

7 Concomitant Use of Immunosuppressive Therapy with Tumor Necrosis Factor (TNF)