Capability of Tofacitinib or Etanercept to Accelerate Tapering of NSAID and Treat-to-target Guided De-escalation of Corticosteroids in RA Patients

Prior treatment

• Previous use of Tofacitinib or other Janus-Kinase (JAK)-inhibitors
• Previous use of Etanercept
• Previous use of any biological agent for RA
  • which was stopped due to lack of efficacy
  • one previous use of biological stopped due to intolerance will be allowed
• CS treatment with dosages \>10 mg at BL
• Previous use of Celecoxib as analgesic therapy which was stopped due to lack of efficacy or intolerance
• Concomitant diseases with chronic pain syndrome or need of extended dosages or long-term treatment with the maximum dosages of NSAID/analgesics (according to SmPC) due to other concomitant diseases/pain symptoms in discretion of the treating physician Exclusion criteria related to general health
• Patients with latent Tb, that are not pre-treated for at least 1 month and planned to be treated 9 months in total with Isozid once a day
• Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and with the study outcome
• Alcohol, drug or chemical abuse Exclusion criteria related to prior treatments

Other illness

• Known hypersensitivity to any component of the study medication (TOFA, ETA, Celecoxib)
• Patients with other chronic inflammatory articular disease or systemic autoimmune disease
• Patients with active Tuberculosis (Tb) (evaluation of Tb according to local standards in clinical care)
• Any active infection, a history of recurrent clinically significant infections (e.g. human immune deficiency virus (HIV)), or a history of recurrent bacterial infections with encapsulated organisms
• Current malignancy or history of malignancies except adequately treated or excised basal cell or squamous cell carcinoma or cervical carcinoma in situ.
• History of a severe psychological illness or condition
• Known hypersensitivity to sulfonamides
• Active peptic ulceration or gastrointestinal (GI) bleeding
• Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid (aspirin) or other NSAIDs including Cyclooxigenase (COX)-2 inhibitors
• Inflammatory bowel disease
• Congestive heart failure (New York Heart Association (NYHA) II-IV)
• Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease

Lab values

• Patients of 50 years and older, if they have one or more cardiovascular risk factors (CVRF) defined as:
  • Current cigarette smoking,
  • Known diagnosis of hypertension,
  • HDL \<40 mg/dl,
  • Diabetes mellitus,
  • History of coronary artery disease: history of revascularization procedure, coronary artery bypass grafting, myocardial infarction, cardiac arrest, unstable angina, acute coronary syndrome or
  • History of premature coronary heart disease or sudden death documented in first degree relatives (male relative before 55 years, female relative before 65 years)
• Risk for or history of thrombotic events (e.g. pulmonary embolism or thrombosis) Severe hepatic dysfunction (serum albumin \< 25 g/L or Child-Pugh score ≥ 10)
• Patients with estimated creatinine clearance \< 30 mL/min

Other

• Primary or secondary immunodeficiency
• Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
• Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, intrauterine device (IUD), physical barrier)
• Current participation in another interventional clinical trial or participation within the last 90 days Exclusion criteria related to formal aspects
• Underage or incapable patients

• Patients with active RA and an inadequate response to up to two previous conventional synthetic Disease modifying anti-rheumatic drug (csDMARD) treatments (methotrexate (MTX), leflunomide (LEF),sulfasalazine (SSZ)) with or without ongoing csDMARD therapy
• RA according to ACR classification criteria
• Age 18 - 65 years
• Active RA is defined as
  • DAS28 \> 3.2 and
  • TJC ≥ 3 and SJC ≥ 3
• VAS-pain ≥ 60 mm (0-100 mm)
• Accompanying CS treatment for RA with a stable dosage of ≥ 2mg/d and ≤ 10 mg/d 2 weeks prior to BL (not more than 30% of patients without CS)
• Accompanying need of NSAID or analgesic treatment due to arthritis and in dosages not exceeding the maximum dose according to Summary of Product characteristics (SmPC)
• If ongoing csDMARD treatment, stable treatment will be defined as either
  • MTX treatment with a dosage of ≥ 10 mg/week and ≤ 25 mg/week, continuously for at least 12 weeks prior to Screening (SCR) with a stable dose of MTX for at least 2 weeks prior to BL or
  • LEF treatment with a dosage between 10 to 20 mg/day, continuously for at least 12 weeks prior to SCR with a stable dose of LEF for at least 2 weeks prior to BL or
  • SSZ treatment with dosage between 1 to 3 g/day, continuously for at least 12 weeks prior to SCR with a stable dose of SSZ for at least 2 weeks prior to BL
• Presence of documented negative results for testing of Hepatitis B and C
• Completed SARS-CoV-2-immunisation as currently recommended by the Standing Committee of Vaccination
• Written informed consent obtained prior to the initiation of any protocol-required procedures
• Willingness to comply to study procedures and study protocol