Overview

Population

Patients with a diagnosis of Rheumatoid Arthritis (RA), moderate or high clinical disease activity (CDAI>10) despite conventional synthetic (cs)DMARD(s) therapy for ≥3 months, naïve to biological (b) and targeted synthetic (ts)DMARDs therapy and a maximum of 2 swollen joints (out of 44 joints)

Study design

Randomised multicentre, parallel-arm clinical study

Primary objective

Non-inferiority of the experimental arm (i.e. clinical therapy together with ultrasound guided treatment decision) in comparison to the control arm (clinically guided decision) concerning the proportion of patients reaching low disease activity (CDAI ≤10) and a minimal clinical important improvement (MCII: improvement of ≥6 points if starting from moderate disease activity, any case starting from high disease activity and achieving low disease activity) or remission according to ACR/EULAR index-based remission criteria (CDAI ≤2.8/Boolean remission) at week 24.

Intervention

This is a randomised multicentre, national, parallel-arm clinical study. Patients with a diagnosis of RA, moderate or high clinical disease activity (CDAI>10) despite conventional synthetic (cs)DMARD(s) therapy for ≥3 months, naïve to biological (b) and targeted synthetic (ts)DMARDs therapy and a maximum of 2 swollen joints (out of 44 joints) will be included and randomized to one of the following two strategic arms:

1. Clinical decision strategy: All patients receive a TNF-alpha blocker while continuing background csDMARD(s) therapy. If a CDAI ≤10 is not achieved after 12 weeks, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use at week 12 is at the discretion of the investigator.
2. Clinical plus ultrasound-based decision strategy. All patients in this group will be evaluated by ultrasound at 44 joints. In case of clinically-verified plus ultrasound verified inflammation, patients will receive a TNF-alpha blocker while continuing background csDMARD(s) therapy. If a CDAI ≤10 is not achieved after 12 weeks, patients are again evaluated by ultrasound at 44 joints. In case clinically-verified plus ultrasound-verified inflammation is present, patients are switched to a bDMARD or tsDMARD. The decision on which b/tsDMARD to use is at the discretion of the investigator. In case clinically-verified plus ultrasound-verified inflammation is absent, patients receive step-up pain therapy while background csDMARD(s) will be continued.

Sample size

110 patients

Time plan

• Total duration of the study: 42 months
• Active phase for each patient: 48 weeks (24 weeks for the interventional treatment strategy and 24 weeks for follow-up visit)
• Recruitment: 30 months

Eligibility

Inclusion Criteria:

1. Classification of RA according to the ACR-EULAR 2010 criteria
2. Age of the patients: 18 to 84 years
3. Patients with moderate or high disease activity according to CDAI (>10)
4. Maximum of 2 clinically swollen joints out of a 44-joint count
5. Current stable treatment with a single csDMARD or a combination thereof for at least 3 months
6. No glucocorticoid therapy or stable glucocorticoid dose for at least 4 weeks and at a maximum dose of 5 mg/day prednisone equivalent.
7. No corticosteroid intraarticular injection within 4 weeks
8. Stable or absent dose of NSAIDs for at least 1 week
9. Patients able and willing to give written informed consent and compliant with the requirements of the study protocol

Exclusion Criteria:

1. Previous or current treatment with any b/ts DMARD
2. Complete (clinically evident) destruction of any joint to be investigated by ultrasound as judged by the physician
3. Current RA-related vasculitis or other active systemic (i.e. extraarticular) RA-manifestation except for rheumatoid nodules, which in the opinion of the investigator would expose the study subject to a high risk of morbidity or mortality
4. Initial arthritis manifestations before the age of 18 years
5. Planned surgery within the study period for any of the joints investigated either clinically or by sonography
6. Current severe medical illness requiring hospitalization
7. Active infection or active malignancy at screening <5 years
8. Any contraindication to b/ts DMARDs according to the "Summary of Product Characteristics"
9. Pregnancy or lactation