Safety and Efficacy of the Combination of Diacerein 100 mg Daily and MTX Versus MTX Alone in the Treatment of Early Rheumatoid Arthritis (RA)

Inclusion Criteria:

1. Male or female aged between 18 and 65 years;
2. Active RA of ≥ 3 months duration but < 2 years, diagnosed according to the American College of Rheumatology (ACR) 1987 revised criteria for RA;
3. RA global functional status class I-III;
4. Treatment on an outpatient basis;
5. Treatment with MTX for a minimum of 12 weeks, with stable weekly dose (10-20 mg) for at least 4 weeks before randomisation;
6. Insufficient response to treatment with MTX, with disease activity score DAS28 > 4.0 at the time of screening and randomisation; the DAS28 must not change significantly from screening to baseline visit (change < 0.6);
7. Tender joint count (TJC) ≥ 6 (68 joint count) and swollen joint count (SJC) ≥ 6 (66 joint count) at screening and randomisation;
8. Screening ESR ≥ 28 mm/h;
9. Evidence of adequate contraceptive methods in women of childbearing potential. Female patients of childbearing potential are those who are not surgically sterile or post-menopausal. Adequate contraceptive methods are hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the entire duration of the study;
10. Agreement not to drink alcohol for the duration of the study;
11. Ability and agreement to comply with the requirements of the study protocol;
12. Having given written informed consent to participate in the study.

Exclusion Criteria:

1. History of active inflammatory arthritis other than RA;
2. Any uncontrolled medical condition such as diabetes mellitus, asthma, cardiopulmonary disease, congestive heart failure, neurological disease, etc.;
3. Alcohol abuse, defined as the consumption of more than one glass of beer or wine in a day;
4. Moderate or severe liver disease (cirrhosis, hepatitis, liver insufficiency);
5. Blood anomalies (significant cytopenia);
6. History of, or currently active primary or secondary immunodeficiency;
7. Chronic hepatitis B (HBsAg positive or HBcAb positive with HBV DNA load ≥ 400 copies/ml) or hepatitis C (anti-HCV positive);
8. Current known active, or history of, recurrent bacterial, viral, fungal, mycobacterial or other infections, or any infection requiring hospitalisation or treatment with i.v. antibiotics within 4 weeks prior to randomisation or oral antibiotics within 2 weeks prior to randomisation;
9. Treatment with biologic DMARDs such as TNF antagonists, IL 1 receptor antagonists, IL 6 receptor antagonists, CTLA4Ig within 12 weeks prior to randomisation, and rituximab within 24 weeks prior to randomisation;
10. Treatment with non-biologic DMARDs such as chloroquine, hydroxychloroquine, penicillamine, sulfasalazine within 4 weeks prior to randomisation, leflunomide, parenteral gold, oral gold within 8 weeks prior to randomisation, azathioprine and ciclosporin within 12 weeks prior to randomisation;
11. Treatment with intra-articular injection of a depocorticosteroid within 8 weeks prior to randomisation;
12. Treatment with NSAID or oral corticosteroids, unless the patient has been on a stable dose for at least 4 weeks before randomisation (maximal allowed daily dose of oral corticosteroid equivalent to prednisone 10 mg);
13. Physical therapy and alternative therapies, unless the patient has received them regularly for at least 4 weeks before randomisation;
14. Initiation of chronic treatment with antihistaminics, antidepressants or tranquilisers, within less than 12 weeks before randomisation.