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

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Patients with active rheumatic arthritis (RA) and lack of efficacy of at least one csDMARD (Disease-modifying anti-rheumatic drug) treatment will be randomized to receive either Tofacitinib (TOFA) or etanercept (ETA). The study will be separated into two parts: The capability to decrease and discontinue pain-reducing treatment with a NSAID (non-steroidal anti-inflammatory drug) over the first 12 weeks of treatment will be measured for primary outcome measured using a visual analogue scale (VAS) at week 12 compared to baseline between the two treatment groups.

Starting at week 12, the capability to taper corticosteroid (CS) treatment using a treat-to-target strategy, i.e. when at least low disease activity (LDA-DAS28) is achieved, will be measured in both groups.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. Frank Behrens
• Collaborator: Pfizer
• Treatments: Etanercept; Tofacitinib

Criteria

Inclusion Criteria:

• 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

• Written informed consent obtained prior to the initiation of any protocol-required procedures

• Willingness to comply to study procedures and study protocol

Exclusion Criteria:

• 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

• Known hypersensitivity to any component of the study medication (TOFA, ETA, Celecoxib)

• 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 other chronic inflammatory articular disease or systemic autoimmune disease

• Patients with active Tuberculosis (Tb) (evaluation of Tb according to local standards in clinical care)

• 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

• 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

• Primary or secondary immunodeficiency

• History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised

• 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

• 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

• 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

• Inflammatory bowel disease

• Congestive heart failure (New York Heart Association (NYHA) II-IV)

• Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease

• 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)

• Alcohol, drug or chemical abuse Exclusion criteria related to prior treatments

• Current participation in another interventional clinical trial or participation within the last 90 days Exclusion criteria related to formal aspects

• Underage or incapable patients