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Rheumatoid ArthritisPhase 4RA-BioStopNCT01602302

Ultrasound and Withdrawal of Biological DMARDs in Rheumatoid Arthritis

A Phase 4 study testing bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept) in people with Rheumatoid Arthritis, run by Medical University of Graz at 1 site in Austria.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

biological DMARDs may be stopped in Rheumatoid Arthritis (RA) patients treated with a combination of synthetic DMARD plus bDMARDs which are in persistent clinical remission. The research question of this study is, whether musculoskeletal sonography is a useful biomarker predicting a disease flare after cessation of… Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteAustria
Study dates
Jun 2012to 19 Nov 2020
Phase
Phase 4
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 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patient ≥18 years and <90 years of age
  • Classification of RA according to the ACR/EULAR 2010 criteria
  • Persistent clinical remission as defined by the ACR/EULAR remission criteria for at least 6 months (documented at ≥2 visits)
  • Written informed consent
  • Current treatment with a single csDMARD or a combination of csDMARDs plus a stable dose and administration interval (for the last 6 months) of a TNF-alpha inhibitor
  • No current systemic corticosteroid treatment (stopped for at least 4 weeks), no corticosteroid injection within 4 weeks
  • Stable dose of NSAIDs for at least 1 week

Who cannot join

  • • Current treatment with any investigational drug
  • Current administration interval of the anti-TNF-alpha agent of >11 weeks
  • Complete destruction of any joint to be investigated by sonography
  • Current RA-related vasculitis or other active systemic (i.e. extraarticular) RA- manifestation with the exception of rheumatoid nodules
  • Initial arthritis manifestations before the age of 17 years
  • Planned surgery within the study period or history of surgery of any of the joints to be investigated clinically or by sonography
Show all 11Show fewer
  • Current severe medical illness requiring hospitalization
  • Active infection or active malignancy at screening or infection during the past 4 weeks requiring (even temporary) discontinuation of the anti-TNF-alpha agent
  • Pregnancy or lactation
  • Inability of the patient to follow the protocol
  • Current treatment with Rituximab (MabThera®)

Trial locations and contacts

1 site in 1 country.

Austria1 site

  • Medical University Graz

    Graz, 8036

Other trials in Austria

About this study

Official title: Ultrasound as Biomarker for Withdrawal of Biological DMARDs in Rheumatoid Arthritis

biological DMARDs may be stopped in Rheumatoid Arthritis (RA) patients treated with a combination of synthetic DMARD plus bDMARDs which are in persistent clinical remission. The research question of this study is, whether musculoskeletal sonography is a useful biomarker predicting a disease flare after cessation of bDMARD therapy.

Read the detailed description

Rheumatoid arthritis (RA) is the most common inflammatory joint disease. It is usually treated with synthetic and biologic disease modifying antirheumatic drugs (DMARDs). Up to 35% of patients can achieve clinical remission by the combination these therapies; however, there is considerable uncertainty regarding the management of patients once this clinical state is achieved. The discontinuation of biological agents in patients with persistent clinical remission may be beneficial for the patients and the health care system reducing the risks of long term adverse events and saving costs, respectively. Up to 60% of patients were reported to flare after cessation of anti-tumor necrosis factor alpha (TNF alpha) therapy despite continuation of synthetic DMARDs and up to now there exist no validated biomarkers that predict which patients will suffer a flare and which patients will remain in remission.

Sonography is more and more used as a biomarker in RA. Subclinical inflammation was previously associated with an increased risk for short term clinical relapse and structural deterioration.

The hypothesis of this prospective study is that ultrasound verified subclinical inflammation at the time of bDMARD withdrawal predicts a disease flare at week 16. The investigators plan to recruit RA-patients with persistent clinical remission according to SDAI and no current corticosteroid therapy. At baseline, bDMARD is stopped, synthetic DMARDs are continued. Patients undergo 9 study visits within 52 weeks. Ultrasound examinations of 14 joints as well as clinical and laboratory assessments with calculation of SDAI scores are performed at each visit. Patients are considered to have a disease flare if disease status changes from remission to active disease according to clinical scores. Patients with a flare of the disease are excluded from the active phase of the study and are treated according to current guidelines.

Being tested
bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept)
Keywords
rheumatoid arthritis, ultrasound, remission, biological DMARD
Medical subject headings
Arthritis, Rheumatoid

What participants receive

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

  • bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept)Drug

    Also called Enbrel, Humira, Remicade, Cimzia

    bDMARDS (etanercept, adalimumab, infliximab, certolizumab, golimumab, tocilizumab, abatacept) will be discontinued after baseline visit in all participants

Study groups in NCT01602302
Study groupRoleWhat they receive
single arm ( bDMARD withdrawal )Experimentalsingle arm (bDMARD withdrawal)
Receives: Drug: bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept)

What is being measured

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

  1. PD-signals predict relapse at week 16

    Active inflammation at the time of bDMARD withdrawal indicated by the presence of a PD-score ≥1 in at least one joint out of a sonographic 14-joint count predicts relapse rate at week 16.

    Measured: 16 weeks

Secondary outcomes (10)

  1. PD-signals predict relapse at week 24

    Active inflammation at the time of bDMARD withdrawal indicated by the presence of a PD-score ≥1 in at least one joint out of a sonographic 14-joint count predicts relapse rate at week 24

    Measured: 24 weeks

  2. PD-signals predict relapse at week 52

    Active inflammation at the time of bDMARD withdrawal indicated by the presence of a PD-score ≥1 in at least one joint out of a sonographic 14-joint count predicts relapse rate at week 52

    Measured: 52 weeks

  3. PD-scores at time of relapse

    RA-patients have higher PD-scores at time of a clinical flare compared to patients with maintained clinical remission

    Measured: 24 weeks

  4. Increment of PD-scores precede flare

    An increment of PD-scores at follow-up compared to baseline visits precedes a clinical flare

    Measured: 52 weeks

  5. PD scores better predict a relapse than residual swollen joints

    PD scores better predict a relapse at week 16, 24 and 52 than the presence of residual swollen joints

    Measured: 16, 24, 52 weeks

  6. PD score at baseline correlates with relapse risk

    The higher the PD score at baseline, the more likely is a relapse at weeks 16, 24 and/or 52

    Measured: 52 weeks

  7. 7. Patients converting from a rheumatoid factor (RF) positive to a RF negative status are less likely to experience a relapse at weeks 16, 24 and 52 than patients remaining seropositive

    1. Patients converting from a rheumatoid factor (RF) positive to a RF negative status are less likely to experience a relapse at weeks 16, 24 and 52 than patients remaining seropositive

    Measured: 16, 24, 52 weeks

  8. 8. Blood biomarkers predict the time to flare after bDMARD withdrawal

    1. Blood biomarkers predict the time to flare after bDMARD withdrawal

  9. 9. Blood biomarkers predict the time to re-achieve remission after flare and re-induction of bDMARD treatment

    1. Blood biomarkers predict the time to re-achieve remission after flare and re-induction of bDMARD treatment

  10. PD-scores and blood biomarkers at baseline predict radiographic progression at week 52

    PD-scores and blood biomarkers at baseline predict radiographic progression at week 52

    Measured: 52

Timeline

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

  1. First posted18 May 2012 (estimated)
  2. Study startJun 2012
  3. Primary completion19 Nov 2020
  4. Study completion19 Nov 2020

Why it stopped: low recruitment

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01602302
Sponsor's protocol ID
2011-5; V2
Other IDs
2011-005204-15
Acronym
RA-BioStop
Status last verified
Nov 2020
First submitted
16 May 2012
Last updated
1 Dec 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Dejaco C, Gessl I, Husic R, Mitter G, Deimel T, Lackner A, Supp G, Hermann J, Smolen J, Stradner MH, Aletaha D, Schwantzer G, Mandl P. Ultrasound-based withdrawal of biologics in rheumatoid arthritis (RA-BioStop). RMD Open. 2026 Aug 7;12(3):e007003. doi: 10.1136/rmdopen-2026-007003.

    PubMed 42567558

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing bDMARD withdrawal (etanercept, adalimumab, infliximab, certolizumab, golimumab, tozilizumab, abatacept) in people with Rheumatoid Arthritis, run by Medical University of Graz at 1 site in Austria.

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 7 inclusion and 11 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: stopped early, as of the sponsor's last update on 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: low recruitment). Results are not available in the source record.

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?

PD-signals predict relapse at week 16 (time frame: 16 weeks). 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 NCT01602302, which also lists 1 linked publication.

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 1 Dec 2020.

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