T Cells and TNF (Tumor Necrosis Factor): The Impact of TNF Blockade

January 6, 2020 updated by: Imperial College London

T Cells and TNF: The Impact of TNF Blockade on Effector T Cell Populations in Rheumatoid Arthritis and Other Conditions Treated With Anti-TNFalpha Agents

We aim to translate these findings into patients with rheumatoid arthritis and other conditions treated with anti-TNF (anti-tumor necrosis factor) therapy, such as psoriatic arthritis and ankylosing spondylitis. Patients from rheumatology clinics within NHS (National Health Service) trusts will be recruited. We will correlate disease activity assessed by clinical parameters, ultrasonography, and questionnaires with biomarkers in the blood and target tissues, such as synovium and skin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Inflammatory arthritis particularly rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis are potentially disabling conditions which cause joint pain, swelling and deformity and treatments are aimed at preventing these complications. Although treatment has improved with the advent of anti TNF alpha therapies, up to 30% of patients fail to respond to this treatment and in others, treatment is associated with significant side effects. The precise mechanisms of this remain unclear. In addition, there are no sensitive methods available to monitor or predict disease response to treatment aside from testing inflammatory markers in the blood. Understanding the mechanism of action and what governs response to anti TNF therapy will allow development of more specific therapies for inflammatory arthritis. Work in animal models of rheumatoid arthritis has characterised a novel cell type, Th17 cells, important in the inflammatory cascade which are affected in a particular way by anti TNF therapies and may underpin their mechanism of action and side effects.

Study Type

Observational

Enrollment (Actual)

48

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

  • United Kingdom
      • London, United Kingdom, W6 8RF
        • Kennedy Institute Clinical Trials Unit, 4Wl, Charing Cross Hospital

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Primary care clinic

Description

Inclusion criteria:

  • Only anti-TNF naïve patients will be included in this study
  • Patients between 18 to 80 years of age
  • Patients due to start treatment with anti-TNF blocking agents - etanercept or adalimumab

Patients with rheumatoid arthritis

  • Only patients meeting the 1987 American College of Rheumatology (ACR) revised classification criteria for rheumatoid arthritis will be included
  • Patients should have active rheumatoid arthritis, defined by an initial DAS28 score >5.1
  • Patients should have at least 1 joint suitable for synovial biopsy
  • Patients can be on concurrent DMARDs but they should have been on a stable dose of DMARD for at least 1 month prior to study entry
  • Patients can be on a concurrent dose of glucocorticoids (up to 10mg daily) and they should have been on a stable dose for at least 4 weeks prior to study entry

Patients with psoriatic arthritis

  • Patients should have a secure diagnosis of psoriatic arthritis determined by a rheumatologist
  • Patients with psoriatic arthritis included in this study should have evidence of concurrent psoriatic skin lesions at the time of study entry
  • Patients should have at least one joint suitable for synovial biopsy
  • Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry

Patients with Ankylosing spondylitis

  • Patient should fulfil the Modified New York Criteria for diagnosis of ankylosing spondylitis
  • Patients can be on concurrent NSAIDs
  • Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry

Exclusion Criteria:

  • Patients who have been previously treated with anti-TNF therapy for whatever reason
  • Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who do not fulfil the diagnostic criteria for these conditions as above
  • Patient who have received an intra-articular injection of steroids or have received an intra-muscular injection of depot steroid to treat disease flare in the preceding 4 weeks prior to commencing anti-TNF therapy.
  • Patients with intercurrent, active infection of any type, excluding the common cold

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Rheumatoid arthritis
Participants with Rheumatoid arthritis
Drug: anti-TNF therapy (etanercept or adalimumab)
Biological DMARD
Other Names:
  • Humira
  • Enbrel
Ankylosing spondylitis
Participants with Ankylosing spondylitis
Drug: anti-TNF therapy (etanercept or adalimumab)
Biological DMARD
Other Names:
  • Humira
  • Enbrel
Psoriatic arthritis
Participants with Psoriatic arthritis
Drug: anti-TNF therapy (etanercept or adalimumab)
Biological DMARD
Other Names:
  • Humira
  • Enbrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood
Time Frame: Week 0, Week 12
The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).
Week 0, Week 12

Collaborators and Investigators

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

Sponsor

Imperial College London

Investigators

  • Principal Investigator: Sonya Abraham, Imperial College London

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)

April 1, 2010

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

January 29, 2010

First Submitted That Met QC Criteria

January 29, 2010

First Posted (Estimate)

February 2, 2010

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 6, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2104091

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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