Algorithms Outperform Metabolite Tests in Predicting Response of Patients With Inflammatory Bowel Disease to Thiopurines

Waljee, Akbar K.; Joyce, Joel C.; Wang, Sijian; Saxena, Aditi; Hart, Margaret; Zhu, Ji; Higgins, Peter

doi:10.1016/j.cgh.2009.09.031

Cited by 73 publications

(70 citation statements)

References 17 publications

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“…If metabolite levels do correlate to these routine labs or even to clinical activity, monitoring these levels can better guide us in optimizing the safety of the drug as well as in assessing patients' disease activity. Others have suggested that clinical algorithms based on routine labs may provide equivalent information at less cost [9] . The first aim this study is to determine the incidence of lymphopenia (defined by absolute lymphocyte count <1000) in patients with IBD with and without treatment using the immunosuppressives AZA/6MP.…”

Section: Lymphopenia In Inflammatory Bowel Disease Patients On Immunomentioning

confidence: 99%

Lymphopenia in Inflammatory Bowel Disease Patients on Immunosuppressive Medications

Abraham

Sellin

2016

Journal of Gastroenterology and Hepatology Research

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Azathioprine and 6-mercaptopurine (AZA/6MP) are effective immunosuppressives used for the treatment of inflammatory bowel disease. The optimal strategy for monitoring therapeutic efficacy and adequate immunosuppression remains to be defined. White blood cell count, mean corpuscle volume (MCV), and 6-mercaptopurine metabolites (6TGN, 6MMP) have all been suggested as potential parameters to monitor efficacy and safety. However, immunomodulators target lymphocytes specifically rather than leukocytes overall; little data is available on the relationship between lymphocytes and immunomodulators in IBD. This study evaluates the incidence of lymphopenia with immunosuppressive use, and correlates metabolite levels (6TGN and 6MMP) with leukocyte, lymphocyte, and MCV levels in IBD patients treated with AZA/6MP. Medical records of 125 adult IBD patients were analyzed based on the use of AZA/6MP, blood counts, and mercaptopurine metabolites 6TGN and 6MMP. Forty three percent of patients taking AZA/6MP developed lymphopenia. Of those with lymphopenia, only 11% had leukopenia. A low but statistically significant correlation of r = -0.3 (p=0.04) for 6TGN to leukocyte counts as well as to MCV levels was found. No correlation between 6TGN levels and lymphocyte counts was noted. This analysis shows that not only leukocyte counts but lymphocyte counts should be monitored closely in patients on these immunosuppressives. Metabolite markers do not provide information regarding who will develop lymphopenia. Consequences of lymphopenia such as opportunistic infections need to be discussed with patients prior to starting this type of therapy.

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Section: Lymphopenia In Inflammatory Bowel Disease Patients On Immunomentioning

confidence: 99%

Lymphopenia in Inflammatory Bowel Disease Patients on Immunosuppressive Medications

Abraham

Sellin

2016

Journal of Gastroenterology and Hepatology Research

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“…Further work on the costeff ectiveness of these diff erent approaches are warranted to inform optimal approaches to drug monitoring in thiopurine therapy. Several alternatives to the measurement of metabolites have been suggested, which are less costly, including measuring the change in the red blood cell mean corpuscular volume, assessing lymphocyte counts, white blood cell count, and machine learning algorithms ( 69,70 ). Th ese factors, although of interest, have not yet been adequately assessed in a prospective randomized manner.…”

Section: Azathioprine/6-mercaptopurinementioning

confidence: 99%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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“…In this fourth group of patients, another class of therapeutic agent is required. Metabolite testing is not the only research pathway as outlined by a recent study by Waljee et al [76]. They investigated whether patterns in common laboratory parameters might be used to identify appropriate immunologic responses to TP and whether they are more accurate than measurements of TP metabolites in identifying patient who respond to therapy.…”

Section: Groupmentioning

confidence: 99%

Thiopurine metabolism monitoring: implications in inflammatory bowel diseases

Dewit

Stärkel

Roblin

2010

Eur J Clin Investigation

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Algorithms Outperform Metabolite Tests in Predicting Response of Patients With Inflammatory Bowel Disease to Thiopurines

Cited by 73 publications

References 17 publications

Lymphopenia in Inflammatory Bowel Disease Patients on Immunosuppressive Medications

Lymphopenia in Inflammatory Bowel Disease Patients on Immunosuppressive Medications

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Thiopurine metabolism monitoring: implications in inflammatory bowel diseases

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