Golimumab Trough Levels in Patients With Ulcerative Colitis (GLMLEVEL)

April 13, 2022 updated by: Carlos Taxonera, Hospital San Carlos, Madrid

Association of Golimumab Trough Levels With Endoscopic and Histologic Healing in Patients With Ulcerative Colitis

Proactive therapeutic drug monitoring of Anti-TNFs with drug titration to a therapeutic window is associated with favorable long-term therapeutic outcomes in IBD and may be superior to reactive therapeutic drug monitoring. Moreover, many exposure-response relationship studies have shown that higher serum anti-TNF drug concentrations are associated with better clinical outcomes in IBD, suggesting that it is maybe time to go from a 'treat-to-target' to a 'treat-to trough' therapeutic approach. In this scenario, there are very limited data regarding therapeutic drug monitoring with golimumab in UC and even no data regarding a therapeutic window to target for important objectives outcomes like mucosal healing and histological remission.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Tumor necrosis factor (TNF)-α antagonists have changed the goals of ulcerative colitis (UC) treatment, with the focus now on preventing disease progression rather than just controlling symptoms. Anti-TNF agents have shown ability to achieve clinical remission and mucosal healing in UC. However, histological remission represents a target distinct from endoscopic healing in UC, and seems a better predictor of clinical outcomes. Moreover, histological remission and not mucosal healing has been associated with a reduced risk of colorectal cancer in UC. Infliximab was reported to induce histological remission in a significant proportion of UC patients. More recently, adalimumab was able to achieve histological remission in nearly one-third of anti-TNF naïve patients with moderately to severely active UC.

Reactive therapeutic drug monitoring of anti-TNF agents may help to identify mechanisms for loss of response and to guide selection of optimal intervention in individual patients and has been shown to be cost-effective compared with empiric dose escalation. Proactive therapeutic drug monitoring showed that anti-TNF trough levels are correlated with clinical response, clinical remission and mucosal healing in patients with inflammatory bowel disease (IBD). Conversely, inadequate serum drug concentrations and antidrug antibodies are associated with poor clinical outcomes. Recently, a study demonstrated that infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in patients with UC.

Golimumab, a subcutaneously administered fully human antibody to TNF, induces clinical response and remission in patients with moderately to severely active UC. In patients who responded to induction therapy, golimumab doses administered every 4 weeks as a maintenance regimen was effective in maintaining clinical response through 1 year. Available data on golimumab drug monitoring and exposure-response relationship in UC patients are from the PURSUIT trials. A positive association between golimumab levels and efficacy outcomes, including mucosal healing, was confirmed during both induction and maintenance portions of the PURSUIT studies.

Real life data regarding golimumab concentrations and clinical outcomes are lacking, with only a small observational study published. Besides, there are no data regarding the ability of golimumab to achieve histological remission in UC patients.

Study Type

Observational

Enrollment (Actual)

52

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Madrid, Spain, 28041
        • Hospital 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital Gregorio Marañón
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46026
        • Hospital Universitario la Fe
    • Madrid
      • Alcorcón, Madrid, Spain, 28922
        • Hospital Universitario Fundacion Alcorcon
      • Fuenlabrada, Madrid, Spain, 28942
        • Hospital Universitario Fuenlabrada
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Puerta de Hierro
      • San Sebastián De Los Reyes, Madrid, Spain, 28703
        • Hospital Infanta Sofía
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Complejo Hospitalario de Navarra

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Eligible patients will include patients of at least 18 years old with moderate to severe UC treated with maintenance therapy with golimumab according to usual clinical practice and have received the induction regimen with the drug according to the EU label, followed by maintenance treatment for at least 6 months from the first dose of drug.

The study population will comprise all consecutive patients in which a programmed colonoscopy is indicated according to clinical practice for one of the following reasons:

  1. Based on a treat-to-target strategy
  2. Screening for prevention of colorectal cancer ( >8 years disease)
  3. In case of flare
  4. In case of long term remission

Description

Inclusion Criteria:

  • Age greater than or equal to 18 years.
  • Patients with a diagnosis of ulcerative colitis at least 12 months prior to the start of the study.
  • Patients previously treated with golimumab for ulcerative colitis prescribed according to the usual clinical practice of each center and who have received at least 5 maintenance doses according to the guidelines accepted in the technical file.
  • Sign of informed consent.

Exclusion Criteria:

  • Patients with Crohn's disease or colitis pending classification
  • Alterations in the coagulation that contraindicate the taking of biopsies
  • Patients with moderate-severe heart failure (grades III / IV NYHA)
  • Patients with tuberculosis or other serious infections such as septicemia, abscesses and opportunistic infections
  • Psychiatric illness that discourages participation in the study
  • Patients with a history of hypersensitivity to golimumab, to other murine proteins or to any of the excipients included in the golimumab data sheet
  • Withdrawal of the informed consent by the patient
  • Any other condition that in the opinion of the investigator discourages the participation of the subject in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between Golimumab trough levels and Endoscopic remission
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
defined as a Mayo endoscopic subscore of 0
Cross-Sectional: 15 days before or after the extraction of levels
Correlation between Golimumab trough levels and Endoscopic healing
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
defined as a Mayo endoscopic subscore of 0 or 1
Cross-Sectional: 15 days before or after the extraction of levels
Correlation between Golimumab trough levels and Histological remission
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
defined as a Geboes index ≤3.0
Cross-Sectional: 15 days before or after the extraction of levels

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between Golimumab trough levels and Clinical remission
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
defined as a total Mayo score ≤2 with no individual subscore exceeding 1 point
Cross-Sectional: 15 days before or after the extraction of levels
Correlation between Golimumab trough levels and Clinical response
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
defined as a decrease from baseline in the total Mayo score of at least 3-points
Cross-Sectional: 15 days before or after the extraction of levels
Receiver operating characteristic curve analysis
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
Thresholds of golimumab levels for outcomes 1 to 5 will be determined using the receiver operating characteristic curve analysis.
Cross-Sectional: 15 days before or after the extraction of levels
C-reactive protein and fecal calprotectin.
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
Correlation between Golimumab trough levels with C-reactive protein and fecal calprotectin.
Cross-Sectional: 15 days before or after the extraction of levels
Histological remission
Time Frame: Cross-Sectional: 15 days before or after the extraction of levels
Proportion of patients with Histological remission defined as a Geboes index ≤3.0
Cross-Sectional: 15 days before or after the extraction of levels

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital San Carlos, Madrid

Collaborators

Merck Sharp & Dohme LLC
Hospital Universitario Ramon y Cajal
Complejo Hospitalario de Navarra
Hospital Universitario 12 de Octubre
Puerta de Hierro University Hospital
Hospital Universitario La Fe
Hospital Universitario La Paz
Hospital Universitario Fundación Alcorcón
Hospital Universitario de Fuenlabrada
Hospital Clínico Universitario de Valencia
Gregorio Marañón Hospital
Hospital Infanta Sofia

Investigators

  • Principal Investigator: Carlos Taxonera, Dr., Hospital San Carlos, Madrid

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Actual)

September 30, 2021

Study Completion (Actual)

September 30, 2021

Study Registration Dates

First Submitted

November 25, 2018

First Submitted That Met QC Criteria

December 10, 2018

First Posted (Actual)

December 12, 2018

Study Record Updates

Last Update Posted (Actual)

April 15, 2022

Last Update Submitted That Met QC Criteria

April 13, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTS-GOL-2018-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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