Ultrasound and Anti-TNF Alpha Withdrawal 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 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.
  
  

• 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
  
  

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

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.