Clinical trial NCT03773445: Golimumab Trough Levels in Patients With Ulcerative Colitis
Official title: Association of Golimumab Trough Levels With Endoscopic and Histologic Healing in Patients With Ulcerative Colitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
Keywords: ulcerative colitis
golimumab
simponi
therapeutic drug monitoring
endoscopic healing
histologic remission
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
Collaborators: name: Hospital Universitario La Fe
name: Hospital Universitario 12 de Octubre
name: Hospital Universitario Ramon y Cajal
name: Gregorio Marañón Hospital
name: Complejo Hospitalario de Navarra
name: Hospital Universitario Fundación Alcorcón
name: Hospital Infanta Sofia
name: Hospital Clínico Universitario de Valencia
name: Puerta de Hierro University Hospital
name: Hospital Universitario La Paz
name: Hospital Universitario de Fuenlabrada
name: Merck Sharp & Dohme LLC
First posted: 2018-12-12
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Correlation between Golimumab trough levels and Endoscopic remission
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: Correlation between Golimumab trough levels and Endoscopic healing
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: Correlation between Golimumab trough levels and Histological remission
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
Secondary outcomes:
measure: Correlation between Golimumab trough levels and Clinical remission
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: Correlation between Golimumab trough levels and Clinical response
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: Receiver operating characteristic curve analysis
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: C-reactive protein and fecal calprotectin.
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
measure: Histological remission
timeFrame: Cross-Sectional: 15 days before or after the extraction of levels
Other outcomes:
Locations:
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Fuenlabrada
country: Spain
facility: Hospital Universitario Fuenlabrada
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: San Sebastián De Los Reyes
country: Spain
facility: Hospital Infanta Sofia
state: Madrid
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
Study officials:
affiliation: Hospital San Carlos, Madrid
name: Carlos Taxonera, Dr.
role: PRINCIPAL_INVESTIGATOR
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