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Ulcerative ColitisGLMLEVELNCT03773445

Golimumab Trough Levels in Patients With Ulcerative Colitis

An observational study of Ulcerative Colitis, run by Hospital San Carlos, Madrid at 12 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ulcerative Colitis
What is being tested?
Golimumab trough levels, Antibodies to golimumab and Histology
Type of treatment
Injection or infusion
How many people
52 participants
Where
12 sitesSpain
Study dates
1 Mar 2019to 30 Sep 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Spain12 sites

  • Hospital Universitario Fundación Alcorcón

    Alcorcón, Madrid, 28922

  • Hospital Universitario Fuenlabrada

    Fuenlabrada, Madrid, 28942

  • Hospital Gregorio Marañón

    Madrid, 28007

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Puerta de Hierro

    Majadahonda, Madrid, 28222

  • Complejo Hospitalario de Navarra

    Pamplona, Navarre, 31008

  • Hospital Infanta Sofia

    San Sebastián de los Reyes, Madrid, 28703

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Universitario La Fe

    Valencia, 46026

Other trials in Spain

About this study

Official title: 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.

Read the 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.

Being tested
Golimumab trough levels, Antibodies to golimumab, Histology, Colonoscopy
Keywords
ulcerative colitis, golimumab, simponi, therapeutic drug monitoring, endoscopic healing, histologic remission
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Correlation between Golimumab trough levels and Endoscopic remission

    defined as a Mayo endoscopic subscore of 0

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

  2. Correlation between Golimumab trough levels and Endoscopic healing

    defined as a Mayo endoscopic subscore of 0 or 1

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

  3. Correlation between Golimumab trough levels and Histological remission

    defined as a Geboes index ≤3.0

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

Secondary outcomes (5)

  1. Correlation between Golimumab trough levels and Clinical remission

    defined as a total Mayo score ≤2 with no individual subscore exceeding 1 point

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

  2. Correlation between Golimumab trough levels and Clinical response

    defined as a decrease from baseline in the total Mayo score of at least 3-points

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

  3. Receiver operating characteristic curve analysis

    Thresholds of golimumab levels for outcomes 1 to 5 will be determined using the receiver operating characteristic curve analysis.

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

  4. C-reactive protein and fecal calprotectin.

    Correlation between Golimumab trough levels with C-reactive protein and fecal calprotectin.

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

  5. Histological remission

    Proportion of patients with Histological remission defined as a Geboes index ≤3.0

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2018
  2. Study start1 Mar 2019
  3. Primary completion30 Sep 2021
  4. Study completion30 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Cross-sectional
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03773445
Sponsor's protocol ID
CTS-GOL-2018-01
Acronym
GLMLEVEL
Status last verified
Apr 2022
First submitted
25 Nov 2018
Last updated
15 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.

    PubMed 16339095

  • 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.

    PubMed 22062358

  • 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.

    PubMed 23735746

  • 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.

    PubMed 23591275

  • 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.

    PubMed 26977756

  • 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.

    PubMed 25986946

  • 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.

    PubMed 14762782

  • 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.

    PubMed 17919486

  • 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.

    PubMed 24803809

  • 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.

    PubMed 26457025

  • 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.

    PubMed 27226417

  • 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.

    PubMed 29372480

  • 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.

    PubMed 23878167

  • 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.

    PubMed 23357488

  • 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.

    PubMed 16931170

Questions about this trial

What is this clinical trial studying?

An observational study of Ulcerative Colitis, run by Hospital San Carlos, Madrid at 12 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Correlation between Golimumab trough levels and Endoscopic remission (time frame: Cross-Sectional: 15 days before or after the extraction of levels). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03773445, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2022.

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