Ultrasound and Anti-TNF Alpha Withdrawal in Rheumatoid Arthritis (RA-BioStop)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Medical University of Graz
Sponsor:
Information provided by (Responsible Party):
Dejaco Christian, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01602302
First received: May 16, 2012
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

TNF-alpha inhibitors may be stopped in Rheumatoid Arthritis (RA) patients treated with a combination of synthetic DMARD plus TNF-alpha inhibitor 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 TNF-alpha inhibitor therapy.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: anti-TNF withdrawal (tanercept, adalimumab, infliximab, certolizumab, golimumab)
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Ultrasound as Biomarker for Anti-TNF Alpha Withdrawal in Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • PD-signals predict relapse at week 16 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Active inflammation at the time of anti-TNFalpha 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.


Secondary Outcome Measures:
  • PD-signals predict relapse at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Active inflammation at the time of anti-TNF alpha 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

  • PD-scores at time of relapse [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    RA-patients have higher PD-scores at time of a clinical flare compared to patients with maintained clinical remission

  • SDAI remission vs DAS28 remission [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    RA-patients with SDAI remission have lower relapse rates compared to patients with DAS28 remission


Estimated Enrollment: 68
Study Start Date: June 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
single arm
single arm (anti-TNF withdrawal)
Drug: anti-TNF withdrawal (tanercept, adalimumab, infliximab, certolizumab, golimumab)
Anti-TNF drug (etanercept, adalimumab, infliximab, certolizumab, golimumab) will be discontinued after baseline visit in all participants
Other Names:
  • Enbrel
  • Humira
  • Remicade
  • Cimzia
  • Simponi

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 anti-TNF withdrawal predicts a disease flare at week 16. The investigators plan to recruit RA-patients with persistent clinical remission according to DAS-28 and/or SDAI and no current corticosteroid therapy. At baseline, anti-TNF alpha therapy is stopped, synthetic DMARDs are continued. Patients undergo 7 study visits within 24 weeks. Ultrasound examinations of 14 joints as well as clinical and laboratory assessments with calculation of DAS-28 and 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 a DAS-28 ≤ 2.6 and/or a SDAI ≤ 3.3 for at least 6 months (documented at ≥ 2 visits)
  • Written informed consent
  • Current treatment with a synthetic DMARD or a combination of them plus a stable dose and administration interval (for the last 6 months) of a TNF-alpha inhibitor as defined above
  • No current corticosteroid treatment (stopped for at least 2 weeks), no corticosteroid injection within 2 weeks
  • Stable dose of NSAIDs for at least 1 week

Exclusion Criteria:

  • Synthetic DMARD and/or anti-TNF alpha dose or administration interval not in accordance with the SRP during the last 6 months before inclusion
  • Current treatment with any investigational drug
  • Complete destruction of joints to be investigated by sonography
  • Instability of the atlanto-axial joint due to active rheumatoid pannus
  • Current RA-related vasculitis or other severe systemic (i.e. not articular) RA- manifestation
  • Begin of arthritis before age of 17 years
  • Planned surgery within the study period or history of surgery (within 2 months) at any of the joints to be investigated clinically or sonographically
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01602302

Contacts
Contact: Christian Dejaco, MD, PhD +43-316-80595 christian.dejaco@gmx.net
Contact: Josef Hermann, MD +43-316-80248 josef.hermann@medunigraz.at

Locations
Austria
Medical University Graz Recruiting
Graz, Austria, 8036
Contact: Christian Dejaco, MD, PhD    +43-316-80595    christian.dejaco@gmx.net   
Principal Investigator: Christian Dejaco, MD, PhD         
Sponsors and Collaborators
Medical University of Graz
Investigators
Principal Investigator: Christian Dejaco, MD, PhD Medical University of Graz
  More Information

No publications provided

Responsible Party: Dejaco Christian, MD, PD, Dr., Medical University of Graz
ClinicalTrials.gov Identifier: NCT01602302     History of Changes
Other Study ID Numbers: 2011-5; V2, 2011-005204-15
Study First Received: May 16, 2012
Last Updated: July 15, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Graz:
rheumatoid arthritis
ultrasound
remission
TNF

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Infliximab
Certolizumab pegol
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dermatologic Agents
Gastrointestinal Agents
Central Nervous System Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 16, 2014