Ultrasound and Withdrawal of Biological DMARDs in Rheumatoid Arthritis (RA-BioStop)

Medical University of Graz

Status and phase

Terminated

Phase 4

Conditions

Rheumatoid Arthritis

Treatments

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

Study type

Interventional

Funder types

Other

Identifiers

NCT01602302

2011-005204-15 (EudraCT Number)

2011-5 V2;

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

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 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

Exclusion criteria

• 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
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®)