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

• PD-signals predict relapse at week 16 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  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.
  
  

• PD-signals predict relapse at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  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
  
  
• PD-signals predict relapse at week 52 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  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
  
  
• 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
  
  
• Increment of PD-scores precede flare [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  An increment of PD-scores at follow-up compared to baseline visits precedes a clinical flare
  
  
• PD scores better predict a relapse than residual swollen joints [ Time Frame: 16, 24, 52 weeks ] [ Designated as safety issue: No ]
  PD scores better predict a relapse at week 16, 24 and 52 than the presence of residual swollen joints
  
  
• PD score at baseline correlates with relapse risk [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  The higher the PD score at baseline, the more likely is a relapse at weeks 16, 24 and/or 52
  
  
• 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 [ Time Frame: 16, 24, 52 weeks ] [ Designated as safety issue: No ]
  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
  
  
• 8. Blood biomarkers predict the time to flare after bDMARD withdrawal [ Designated as safety issue: No ]
  8. Blood biomarkers predict the time to flare after bDMARD withdrawal
  
  
• 9. Blood biomarkers predict the time to re-achieve remission after flare and re-induction of bDMARD treatment [ Designated as safety issue: No ]
  9. Blood biomarkers predict the time to re-achieve remission after flare and re-induction of bDMARD treatment
  
  
• PD-scores and blood biomarkers at baseline predict radiographic progression at week 52 [ Time Frame: 52 ] [ Designated as safety issue: No ]
  PD-scores and blood biomarkers at baseline predict radiographic progression at week 52
  
  

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.