Tapering of Biologics in Inflammatory Arthritis Patients in Remission

Study Purpose

Rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA) are types of inflammatory arthritis. They are disabling conditions caused by inflammation in joints that can lead to pain, stiffness, fatigue and joint damage. There is currently no cure but treatment is aimed at reducing joint inflammation. Some of the most promising new therapies work by interfering with the binding of a molecule called tumour necrosis factor (TNF). In recent years, new anti-TNF drugs (such as adalimumab, etanercept and certolizumab) have been developed that block the action of TNF and reduce this inflammation. These drugs are very effective in controlling inflammation for many patients whose arthritis has not responded to other therapies. Some patients can take these medications for a long time. If a patient is stable on their rheumatoid arthritis biologic or biosimilar, tapering the drug is often considered. The investigators are planning to look at drug level and anti-drug antibody testing to guide anti-TNF tapering (reducing) decisions in UK patients with RA who have stable, reduced arthritis symptoms. The investigators think that measuring these drug levels and anti-drug antibodies in blood samples will be useful for guiding this process, but the investigators can't be sure. It is important to do this safely so the patient doesn't experience a flare of their disease symptoms. The study will be used to determine whether a much larger study to assess the usefulness of these measurements would be achievable. This study will assess whether measuring biomarkers (measurable substances in the blood) that may affect a patient's response to treatment. If a patient are eligible to take part, they will be randomly allocated to one of the following groups; - Their Doctor receiving information and treatment advice based on their blood results or - Their Doctor not receiving this information

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Patients must have RA according to the American College of Rheumatology (ACR) 1987 or 2010 criteria 2. Patients must be willing and able to participate in the study (including follow up visits and providing blood samples) after providing informed consent. 3. Patients must currently be on stable treatment a one of the following single anti-TNF agents Adalimumab, Etanercept or Certolizumab. They must have been taking this biologic/ biosimilar therapy for a minimum of 12 months 4. Patients must be in remission with a DAS28 CRP of less than or equal to 2.6. 5. A DAS28 score must be provided at baseline. This must have been taken within the month before study recruitment. If this DAS score is not available, the patient is not eligible to take part. 6. Consultant must be looking to taper patient's standard care medication 7. Aged 18 years or over

Exclusion Criteria:

1. Anyone who has switched anti-TNF agent in the last 12 months 2. Anyone without a recent DAS score (within the previous month) 3. Anyone taking any anti-TNF therapy that isn't Adalimumab, Etanercept or Certolizumab. 4. Anyone who has received steroids within past 3 months (enteral, parenteral or intra-articular) 5. Anyone who is currently pregnancy, or pregnancy planned within next 6 months 6. Anyone with any planned major surgery 7. Anyone with the inability to provide informed consent

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04429776
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Manchester
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Rheumatoid Arthritis, Psoriatic Arthritis
Additional Details

Participants will be randomly allocated to feedback of their drug levels / antidrug antibody status to their consultant prior to tapering, or not, in a 1:1 ratio.

  • - Those participants randomised to the group where no feedback is required will have their dosing interval doubled (from 2 to 4 weeks for certolizumab and adalimumab; from 1 to 2 weeks for etanercept).
  • - For participants randomised to the arm where results are received by the treating clinician, advice will accompany the results.
It will be made clear that this is advice only and that the ultimate treatment decisions rest with the treating clinician. Patients would be recruited at the point at which the decision is made to begin tapering their biologic. The NHS site teams will be informed which arm of the study the participant has been randomised to, as they will be made aware of patient test results. Participants will not be blinded to which intervention they receive. University of Manchester Researchers undertaking the laboratory tests and those entering study data will be blinded. The consent form, registration form, baseline CRF and baseline participant questionnaire should then be returned to the study coordinator at CfMR in the pre-paid packaging provided. A baseline DAS28 score must be provided. This should be from no more than a month before the date of consent. If this cannot be provided the patient is not eligible to take part. Recruiting teams can start to taper the patient's medication immediately after consent on to the TAPER trial. Blood samples will be taken at the following time points;
  • - Baseline (at the point of consent, when the decision to taper is made) - 6 months after tapering starts - 12 months after tapering starts Participants in TAPER will need to have their blood samples taken the day before their next anti-TNF injection date.
This means the participant will have to come in to their hospital sites at these time points for their sample. Sites will be provided with blood kits for this. These will include a phlebotomy letter, just in case the participant needs to go to a different hospital department to have their bloods taken. These will be returned to the University of Manchester is the pre-paid postage boxes provided. The researchers would like each of the follow-up visits to occur as closely to the 6 month and 12 month time points as possible. However, the researchers will accept the following visit windows; • 6 and 12 month time points; +/- 1 month The University of Manchester will return the blood results to site for participants randomised to the arm where results are returned. This will be sent via email with appropriate treatment advice, as per the information in section 4 within 4 weeks of sample receipt. The site team will receive these results by letter in advance of the follow-up visit and will have the opportunity to discuss these with the Chief Investigator, Prof. Anne Barton, in advance of the visit if required. For participants in the control arm (no feedback of results), the blood samples will be collected and tested in the same way but results will not be provided to the treating clinician.

Arms & Interventions

Arms

Experimental: Feedback Arm

Trough blood samples taken and analysed at baseline, 6m and 12m. Results fed back to recruiting clinical team who can choose to use these to influence their tapering decisions.

Active Comparator: No Feedback Arm

Trough blood samples taken and analysed at baseline, 6m and 12m. Results not fed back to recruiting clinical team.

Interventions

Diagnostic Test: - Drug level testing

These will be carried out at the CfMR labs at the University of Manchester.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Anne C Barton, FRCP PhD

[email protected]

01612760539

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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