Updated: October 9, 2024

CCP: 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

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.

Introduction

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

DrugDose optimizationTime to reassess
VedolizumabEscalate to q4w dosing*At the 3rd q4w dosing
UstekinumabEscalate to q4w dosing OR request IV reloading doseAt the 3rd q4w dosing OR 3 to 4 months after IV reloading dose
Tofacitinib10mg po BIDAfter 8 weeks 
Upadacitinib30mg po bid (for those on 15mg qd)After 8 weeks
RisankizumabN/A
OzanimodN/A

*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(μg/g)InterpretationSuggested Management
<50-100Quiescent disease likelyContinue current therapy
>100-250Inflammation possibleInvestigate (e.g., colonoscopy) to confirm inflammation
>250Inflammation likelyOptimize/switch therapy

Table 3: Approach to managing thiopurine therapy

Etiology of Thiopurine Failure6-TGN Level
(pmol/10^8 erythrocytes)
6-MMP Level (pmol/10^8 erythrocytes)6-MMP/6-TGN RatioProposed Treatment Strategy
Inadequate
dose
Low (<230)Low (<5700)Normal (4-24)Increase dose
Excessive TPMTLow (<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 adherenceLow (<230)Low (<5700)Normal (4-24)Verify adherence
True drug ineffectivenessNormal (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

REFERENCES:

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