NCT03773445

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
52

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Mar 2019

Typical duration for all trials

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 25, 2018

Completed
17 days until next milestone

First Posted

Study publicly available on registry

December 12, 2018

Completed
3 months until next milestone

Study Start

First participant enrolled

March 1, 2019

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2021

Completed
Last Updated

April 15, 2022

Status Verified

April 1, 2022

Enrollment Period

2.6 years

First QC Date

November 25, 2018

Last Update Submit

April 13, 2022

Conditions

Ulcerative Colitis

Keywords

ulcerative colitisgolimumabsimponitherapeutic drug monitoringendoscopic healinghistologic remission

Outcome Measures

Primary Outcomes (3)

  • Correlation between Golimumab trough levels and Endoscopic remission

    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

    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

    defined as a Geboes index ≤3.0

    Cross-Sectional: 15 days before or after the extraction of levels

Secondary Outcomes (5)

  • Correlation between Golimumab trough levels and Clinical remission

    Cross-Sectional: 15 days before or after the extraction of levels

  • Correlation between Golimumab trough levels and Clinical response

    Cross-Sectional: 15 days before or after the extraction of levels

  • Receiver operating characteristic curve analysis

    Cross-Sectional: 15 days before or after the extraction of levels

  • C-reactive protein and fecal calprotectin.

    Cross-Sectional: 15 days before or after the extraction of levels

  • Histological remission

    Cross-Sectional: 15 days before or after the extraction of levels

Interventions

Golimumab trough levelsDIAGNOSTIC_TEST

Golimumab trough levels taken immediately before the administration of the next subcutaneous dose of golimumab

Antibodies to golimumabDIAGNOSTIC_TEST

Antibodies to golimumab taken immediately before the administration of the next subcutaneous dose of golimumab

HistologyDIAGNOSTIC_TEST

Histology of colonic biopsies using the Geboes Index

ColonoscopyDIAGNOSTIC_TEST

Colonoscopy to evaluate the endoscopic activity by a Mayo endoscopic subscore

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital Universitario Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Infanta Sofia

San Sebastián de los Reyes, Madrid, 28703, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Related Publications (25)

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    PMID: 16339095RESULT

  • Sandborn WJ, van Assche G, Reinisch W, Colombel JF, D'Haens G, Wolf DC, Kron M, Tighe MB, Lazar A, Thakkar RB. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012 Feb;142(2):257-65.e1-3. doi: 10.1053/j.gastro.2011.10.032. Epub 2011 Nov 4.

    PMID: 22062358RESULT

  • Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Jarnerot G, Hibi T, Rutgeerts P; PURSUIT-SC Study Group. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):85-95; quiz e14-5. doi: 10.1053/j.gastro.2013.05.048. Epub 2013 Jun 2.

    PMID: 23735746RESULT

  • Rosenberg L, Nanda KS, Zenlea T, Gifford A, Lawlor GO, Falchuk KR, Wolf JL, Cheifetz AS, Goldsmith JD, Moss AC. Histologic markers of inflammation in patients with ulcerative colitis in clinical remission. Clin Gastroenterol Hepatol. 2013 Aug;11(8):991-6. doi: 10.1016/j.cgh.2013.02.030. Epub 2013 Apr 13.

    PMID: 23591275RESULT

  • Zenlea T, Yee EU, Rosenberg L, Boyle M, Nanda KS, Wolf JL, Falchuk KR, Cheifetz AS, Goldsmith JD, Moss AC. Histology Grade Is Independently Associated With Relapse Risk in Patients With Ulcerative Colitis in Clinical Remission: A Prospective Study. Am J Gastroenterol. 2016 May;111(5):685-90. doi: 10.1038/ajg.2016.50. Epub 2016 Mar 15.

    PMID: 26977756RESULT

  • Bryant RV, Burger DC, Delo J, Walsh AJ, Thomas S, von Herbay A, Buchel OC, White L, Brain O, Keshav S, Warren BF, Travis SP. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016 Mar;65(3):408-14. doi: 10.1136/gutjnl-2015-309598. Epub 2015 May 18.

    PMID: 25986946RESULT

  • Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M, Williams C, Price A, Talbot I, Forbes A. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004 Feb;126(2):451-9. doi: 10.1053/j.gastro.2003.11.010.

    PMID: 14762782RESULT

  • Gupta RB, Harpaz N, Itzkowitz S, Hossain S, Matula S, Kornbluth A, Bodian C, Ullman T. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology. 2007 Oct;133(4):1099-105; quiz 1340-1. doi: 10.1053/j.gastro.2007.08.001. Epub 2007 Aug 2.

    PMID: 17919486RESULT

  • Korelitz BI, Sultan K, Kothari M, Arapos L, Schneider J, Panagopoulos G. Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis. World J Gastroenterol. 2014 May 7;20(17):4980-6. doi: 10.3748/wjg.v20.i17.4980.

    PMID: 24803809RESULT

  • Wiernicka A, Szymanska S, Cielecka-Kuszyk J, Dadalski M, Kierkus J. Histological healing after infliximab induction therapy in children with ulcerative colitis. World J Gastroenterol. 2015 Oct 7;21(37):10654-61. doi: 10.3748/wjg.v21.i37.10654.

    PMID: 26457025RESULT

  • Magro F, Lopes SI, Lopes J, Portela F, Cotter J, Lopes S, Moreira MJ, Lago P, Peixe P, Albuquerque A, Rodrigues S, Silva MR, Monteiro P, Lopes C, Monteiro L, Macedo G, Veloso L, Camila C, Afonso J, Geboes K, Carneiro F; Portuguese IBD group [GEDII]. Histological Outcomes and Predictive Value of Faecal Markers in Moderately to Severely Active Ulcerative Colitis Patients Receiving Infliximab. J Crohns Colitis. 2016 Dec;10(12):1407-1416. doi: 10.1093/ecco-jcc/jjw112. Epub 2016 May 25.

    PMID: 27226417RESULT

  • Fernandez-Blanco JI, Fernandez-Diaz G, Cara C, Vera MI, Olivares D, Taxonera C. Adalimumab for Induction of Histological Remission in Moderately to Severely Active Ulcerative Colitis. Dig Dis Sci. 2018 Mar;63(3):731-737. doi: 10.1007/s10620-018-4935-5. Epub 2018 Jan 25.

    PMID: 29372480RESULT

  • Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, Pedersen G, Kjeldsen J, Jacobsen BA, Oxholm AS, Kjellberg J, Bendtzen K, Ainsworth MA. Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial. Gut. 2014 Jun;63(6):919-27. doi: 10.1136/gutjnl-2013-305279. Epub 2013 Jul 22.

    PMID: 23878167RESULT

  • Velayos FS, Kahn JG, Sandborn WJ, Feagan BG. A test-based strategy is more cost effective than empiric dose escalation for patients with Crohn's disease who lose responsiveness to infliximab. Clin Gastroenterol Hepatol. 2013 Jun;11(6):654-66. doi: 10.1016/j.cgh.2012.12.035. Epub 2013 Jan 26.

    PMID: 23357488RESULT

  • Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease. Clin Gastroenterol Hepatol. 2006 Oct;4(10):1248-54. doi: 10.1016/j.cgh.2006.06.025. Epub 2006 Aug 22.

    PMID: 16931170RESULT

  • Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010 Jan;59(1):49-54. doi: 10.1136/gut.2009.183095.

    PMID: 19651627RESULT

  • Paul S, Del Tedesco E, Marotte H, Rinaudo-Gaujous M, Moreau A, Phelip JM, Genin C, Peyrin-Biroulet L, Roblin X. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2013 Nov;19(12):2568-76. doi: 10.1097/MIB.0b013e3182a77b41.

    PMID: 24013361RESULT

  • Vande Casteele N, Ferrante M, Van Assche G, Ballet V, Compernolle G, Van Steen K, Simoens S, Rutgeerts P, Gils A, Vermeire S. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015 Jun;148(7):1320-9.e3. doi: 10.1053/j.gastro.2015.02.031. Epub 2015 Feb 24.

    PMID: 25724455RESULT

  • Cornillie F, Hanauer SB, Diamond RH, Wang J, Tang KL, Xu Z, Rutgeerts P, Vermeire S. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial. Gut. 2014 Nov;63(11):1721-7. doi: 10.1136/gutjnl-2012-304094. Epub 2014 Jan 28.

    PMID: 24474383RESULT

  • Adedokun OJ, Sandborn WJ, Feagan BG, Rutgeerts P, Xu Z, Marano CW, Johanns J, Zhou H, Davis HM, Cornillie F, Reinisch W. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014 Dec;147(6):1296-1307.e5. doi: 10.1053/j.gastro.2014.08.035. Epub 2014 Aug 28.

    PMID: 25173754RESULT

  • Vande Casteele N, Khanna R, Levesque BG, Stitt L, Zou GY, Singh S, Lockton S, Hauenstein S, Ohrmund L, Greenberg GR, Rutgeerts PJ, Gils A, Sandborn WJ, Vermeire S, Feagan BG. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease. Gut. 2015 Oct;64(10):1539-45. doi: 10.1136/gutjnl-2014-307883. Epub 2014 Oct 21.

    PMID: 25336114RESULT

  • Papamichael K, Rakowsky S, Rivera C, Cheifetz AS, Osterman MT. Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis. Aliment Pharmacol Ther. 2018 Feb;47(4):478-484. doi: 10.1111/apt.14458. Epub 2017 Dec 6.

    PMID: 29210094RESULT

  • Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, Adedokun OJ, Guzzo C, Colombel JF, Reinisch W, Gibson PR, Collins J, Jarnerot G, Rutgeerts P; PURSUIT-Maintenance Study Group. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014 Jan;146(1):96-109.e1. doi: 10.1053/j.gastro.2013.06.010. Epub 2013 Jun 14.

    PMID: 23770005RESULT

  • Adedokun OJ, Xu Z, Marano CW, Strauss R, Zhang H, Johanns J, Zhou H, Davis HM, Reinisch W, Feagan BG, Rutgeerts P, Sandborn WJ. Pharmacokinetics and Exposure-response Relationship of Golimumab in Patients with Moderately-to-Severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT Induction and Maintenance Studies. J Crohns Colitis. 2017 Jan;11(1):35-46. doi: 10.1093/ecco-jcc/jjw133. Epub 2016 Jul 20.

    PMID: 27440869RESULT

  • Detrez I, Dreesen E, Van Stappen T, de Vries A, Brouwers E, Van Assche G, Vermeire S, Ferrante M, Gils A. Variability in Golimumab Exposure: A 'Real-Life' Observational Study in Active Ulcerative Colitis. J Crohns Colitis. 2016 May;10(5):575-81. doi: 10.1093/ecco-jcc/jjv241. Epub 2016 Jan 6.

    PMID: 26738756RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and colonic biopsies

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Shadowing Technique, HistologyColonoscopy

Condition Hierarchy (Ancestors)

ColitisGastroenteritisGastrointestinal DiseasesDigestive System DiseasesInflammatory Bowel DiseasesColonic DiseasesIntestinal Diseases

Intervention Hierarchy (Ancestors)

Staining and LabelingHistocytological Preparation TechniquesCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesInvestigative TechniquesEndoscopy, GastrointestinalEndoscopy, Digestive SystemDiagnostic Techniques, Digestive SystemEndoscopyDiagnostic Techniques, SurgicalDigestive System Surgical ProceduresSurgical Procedures, OperativeMinimally Invasive Surgical Procedures

Study Officials

  • Carlos Taxonera, Dr.

    Hospital San Carlos, Madrid

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr.

Study Record Dates

First Submitted

November 25, 2018

First Posted

December 12, 2018

Study Start

March 1, 2019

Primary Completion

September 30, 2021

Study Completion

September 30, 2021

Last Updated

April 15, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will not share

Locations

ES(12)