9410 Carroll Park DriveSan Diego, CA 92121888-423-5227858-824-0896 fax

www.prometheuslabs.com

References:1. Seidman EG. Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD. Rev Gastroenterol Disord.

2003;3(suppl 1):S30-S38.2. Dubinsky MC, Lamothe S, Yang HY, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease.

Gastroenterology. 2000;118(4):705-713.3. Bloomfeld RS, Onken JE. Mercaptopurine metabolite results in clinical gastroenterology practice. Aliment Pharmacol Ther. 2003;17(1):69-73.4. Lichtenstein GR, Abreu MT, Cohen R, Termaine W; American Gastroenterological Association. American Gastroenterological Association Institute medical position

statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130(3):935-939.5. Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis.

Gastroenterology. 2006;130(4):1047-1053.

PROMETHEuS, the Link Design, and For the person in every patient are trademarks or registered trademarks of Prometheus Laboratories Inc. ©2008 Prometheus Laboratories Inc. All rights reserved. PTM08001 4/08 Prometheus products, services, and technology are covered by one or more uS patents and patents pending. For more information, see www.prometheuslabs.com.

To order diagnostic or therapy monitoring tests, please call

Prometheus Client Services at 888-423-5227 or fax to 877-816-4019.

Prometheus diagnostic services provide important information to aid in the diagnosis and management of certain diseases and conditions. How this information is used to guide patient care is the responsibility of the physician.

Classify patients for individualized starting dose of thiopurines

PROMETHEUS® TPMT Genetics PROMETHEUS® TPMT Enzyme

A recently published American Gastroenterological Association Medical Position Statement suggests that individuals should have TPMT genotype or phenotype assessed before initiation of thiopurines.4

PROMETHEUS® Thiopurine Metabolites

“Mean/median 6-TGN levels were higher among patients in

remission than in those with active disease….”

Osterman et al 5

Optimize ongoing dosing of thiopurines to reach and maintain therapeutic goal

From information to insight

PROMETHEUS Diagnostics

Prometheus® TPMT Genetics Prometheus® TPMT Enzyme Prometheus® Thiopurine Metabolites

PROMETHEUS® Thiopurine Management

Classify. Optimize.

From information to insight

PROMETHEUS Diagnostics

CLassify bEfoRE ThERaPy &

oPTiMizE duRinG ThERaPy

Classify. Optimize.

PROMETHEUS® Thiopurine Management

Metabolites monitoring identifies treatment failures who may be converted to responders3,c

individualize dosing for maximal efficacy

before initiating thiopurine therapyWhEn

Why

hoW

CLassify

Knowledge of TPMT guides 3 dosing decisions

1 Normal to high TPMT activity may be interpreted as lower relative risk for myelosuppressiona,1 - Patients may tolerate a full dosing regimen of thiopurine therapy1 - Full dosing may reduce time to response1

2 Intermediate TPMT activity may be interpreted as at risk for myelosupressiona,1

- Reduced thiopurine dose recommended1

3 Low to no TPMT activity may be interpreted as high risk for life-threatening myelosuppression1

- Exclude thiopurine from therapy1

achieve optimal levels to increase the chance of response1

oPTiMizE

WhEn

Why

hoW

PROMETHEUS® TPMT Geneticsb l Genotypic analysis independent of environmental factors

- Blood transfusions - Concomitant medications

PROMETHEUS® TPMT Enzymeb l Detailed phenotypic analysis

aOngoing monitoring of CBCs and LFTs is recommended.

bPrometheus proprietary and patented technology.

The use of 6-MP or azathiopurine in inflammatory bowel disease has not been approved by the FDA.

Thiopurine drug metabolism2 Each individual’s TPMT activity results in differences in metabolism, directly affecting efficacy and risk of toxicity.

Adapted from Dubinsky et al.2

3 to 4 weeks after initiating thiopurine therapy1

inadequate or unexpected response - Suspected lack of patient compliance

Reach therapeutic goal and increase likelihood of response

PROMETHEUS® Thiopurine Metabolitesb

Adapted from Bloomfeld and Onken.3

cBased on 9187 6-MP/azathiopurine metabolite panels reviewed and interpreted by gastroenterologists.

6-TGn (pmol/8 x 108 erythrocytes)

6-MMP (pmol/8 x 108 erythrocytes)

interpretationPatients n (%)

(n = 9187)

Undetectable Undetectable Noncompliance 263 (3%)

< 230 < 5700 Underdosed 4260 (46%)

< 230 > 5700Preferential metabolism

via TPMT pathway534 (6%)

230-450 < 5700 Therapeutic goal 2444 (27%)

230-450 > 5700 Potential hepatotoxicity 552 (6%)

> 450 < 5700Potential TPMT

deficiency (potential myelotoxicity)

936 (10%)

> 1000 UndetectablePotential TPMT absence (potential myelotoxicity)

58 (1%)

> 450 > 5700 Overdosed 140 (2%)

PROMETHEUS® Thiopurine Management

Classify. Optimize.