Loss of Response or Partial Response for Patients on Advanced Therapy

Objective: achieve and maintain remission with advanced therapy

Patient Population: patients diagnosed with inflammatory bowel disease on advanced therapy

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New IBD therapies are continuously becoming available, however the approach to loss of response or partial response for patients on Advanced Therapy remains inconsistent.  The main objective is to achieve and maintain remission by dose optimization and reassessment of response to medications and switching therapies as required.


This CCP recommends a common approach to any IBD patient who is on Advanced Therapy and who is exhibiting symptoms of loss of response or partial response. While initially developed for guidance regarding drug level monitoring and dose optimization for patients losing response to anti-TNF therapies, this CCP also provides suggestions for how to approach patients who are on newer biologics and small molecules. Where applicable, the guidance reflects published data and recommendations established by the global IBD community.   

Table 1: Approach to managing other advanced therapies


Dose optimization

Time to reassess


Escalate to q4w dosing*

At the 3rd q4w dosing


Escalate to q4w dosing OR request IV reloading dose

At the 3rd q4w dosing OR 3 to 4 months after IV reloading dose


10mg po BID

After 8 weeks 


30mg po bid (for those on 15mg qd)

After 8 weeks





*Optimization has limited benefit based on evidence.

Always discuss the potential risks associated with changing advanced therapies with the patient, including the risk of a lesser response and potential side effects. 

Table 2: Fecal Calprotectin results and clinical approach

Fecal Calprotectin



Suggested Management


Quiescent disease likely

Continue current therapy


Inflammation possible

Investigate (e.g., colonoscopy) to confirm inflammation


Inflammation likely

Optimize/switch therapy

Table 3: Approach to managing thiopurine therapy

Etiology of Thiopurine Failure 6-TGN Level
(pmol/10^8 erythrocytes)
6-MMP Level (pmol/10^8 erythrocytes) 6-MMP/6-TGN Ratio Proposed Treatment Strategy


Low (<230) Low (<5700) Normal (4-24) Increase dose
Excessive TPMT Low (<230) High (>5700) High (>24) TPMT modulation by the addition of allopurinol or 5-ASA, dose splitting, switch to alternative agent, such as MTX
Lack of adherence Low (<230) Low (<5700) Normal (4-24) Verify adherence
True drug ineffectiveness Normal (230-400) Normal (<5700) Normal (4-24) Alternative therapy

5-ASA: Mesalamine
6-MMP: 6-methylmercaptopurine
6-TGN: 6-thioguanine nucleotides
MTX: Methotrexate
TPMT: Thiopurine methyltransferase


Papamichael et al. Appropriate Therapeutic Drug Monitoring of Biologic Agents for patients with inflammatory bowel diseases. Clinical Gastroenterology Hepatology. 2019; 17(9):1655-1668. https://doi.org/10.1016/j.cgh.2019.03.037

Feuerstein et al. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017;153(3):827-834. https://doi.org/10.1053/j.gastro.2017.07.032

Mitrev et al. Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases. Aliment Pharmacol Ther 2017; 46(11-12):1037-1053. https://doi.org/10.1111/apt.14368

Bressler et al. Clinician’s guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease. Canadian Journal of Gastroenterology and Hepatology 2015;29(7):369-372. https://doi.org/10.1155/2015/852723

Kopylov et al. Therapeutic drug monitoring in inflammatory bowel disease. Annals of Gastroenterology 2014;27(4):304-312. PMCID: PMC4188926

Turner et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021 Apr;160(5):1570-1583. https://doi.org/10.1053/j.gastro.2020.12.031

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