Golimumab Trough Levels in Patients With Ulcerative Colitis

Completed

• Conditions: Ulcerative Colitis

• Registration Number: NCT03773445
• Lead Sponsor: Hospital San Carlos, Madrid

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-11-25
• Study First Submitted QC: 2018-12-10
• Study First Posted: 2018-12-12
• Study Start: 2019-03-01
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-13
• Last Update Posted: 2022-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Correlation between Golimumab trough levels and Clinical remission	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
Correlation between Golimumab trough levels and Clinical response	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
Receiver operating characteristic curve analysis	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.
Histological remission	Cross-Sectional: 15 days before or after the extraction of levels	Proportion of patients with Histological remission defined as a Geboes index ≤3.0
C-reactive protein and fecal calprotectin.	Cross-Sectional: 15 days before or after the extraction of levels	Correlation between Golimumab trough levels with C-reactive protein and fecal calprotectin.

Trial Locations

Locations (12)

Hospital Universitario Fundación Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario Fuenlabrada; 🇪🇸 Fuenlabrada, Madrid, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Hospital Infanta Sofia; 🇪🇸 San Sebastián De Los Reyes, Madrid, Spain

Complejo Hospitalario de Navarra; 🇪🇸 Pamplona, Navarra, Spain