A Double Blind, Randomized, Placebo Controlled,
Multi-Center Trial of Anti-TNF¨¢
Chimeric Monoclonal Antibody (Infliximab, Remicade®)
in Combination with Methotrexate in Patients with
Very Early Inflammatory Arthritis.

1. Men and women, >= 18 and <= 75 years of age, capable of understanding and signing an informed consent;

2. The presence of arthritis:

a. Must be established in a rheumatology center;

b. Must be present in at least 2 joints of the 66 joint count, of which at least one joint must be an MCP-, or a PIP- (IP-) or a wrist- or a MTP-joint. Two MTP-joints will not
suffice. Any kind of polyarthritis (>= 6 joints of any kind) will be sufficient;

c. Without any previous episodes of inflammatory joint disease;

3. Duration of symptoms :

a. Must be reported by the subject and should involve the inflamed joints described
under 2;

b. Must be 2 weeks at least, according to the algorithm in Table 1 (subjects will not
receive study treatment before 12 weeks of symptom duration according to the
algorithm in Table 1);

c. Must be 16 weeks at most, as reported by the subject, including the observation
period of at least 2 weeks by the physician, according to the algorithm in Table 1;

4. Confirmation of persistent arthritis:

a. Duration must be 2 weeks at least, according to the algorithm in Table 1.

b. Duration must be 12 weeks at most, according to the algorithm in Table 1.

c. Must be documented by the same rheumatology center that established arthritis at the first visit;

d. Must involve at least one of the same joints as were involved at the first visit;

5. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the
study and should continue such precautions for 6 months after receiving the last
medication;

6. Are considered eligible according to the tuberculosis (TB) eligibility assessment,
screening, and early detection of reactivation rules defined in Section 7.14: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation;

7. Chest radiograph (which must not be older than three months at the visit 1/day 0 visit) must show no evidence of malignancy, infection, or fibrosis. The chest radiograph should also show no atypical scarring, cavitary lesions, or calcified granulomas, as evidence of past tuberculosis infections, without a documented history of adequate therapy.

1. Have arthritis with a distinct diagnosis, made after a routine diagnostic work-up
(examples are SLE, psoriatic arthritis, systemic sclerosis, gout, pseudogout, Lyme
arthritis, reactive arthritis, Parvo viral arthritis);

2. Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care;

3. Weigh more than 100 kg;

4. Use glucocorticoids > 10 mg/day prednisone or equivalent;

5. Have received Intramuscular or intra-articular injection of steroids in the previous month;

6. Have Screening laboratory test results as follows:

a. White blood cells (WBCs) < 3.0 x 109 cells/L;

b. Platelets < 100 X 109 cells/L;

c. Serum creatinine > 1.4 mg/dL;

d. Serum transaminase levels exceeding 2 times the upper limit of normal for the site
laboratory;

7. Have had any previous treatment with monoclonal antibodies or antibody fragments;

8. Have a history of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion;

9. Have had prior treatment with MTX and/or other DMARDs (except
hydroxychloroquine);

10. Have documentation of seropositivity for human immunodeficiency virus (HIV);

11. Have documentation of a positive test for hepatitis B surface antigen or hepatitis Cantibodies;

12. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results;

13. Have a known history of serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the previous 3 months;

14. Have a known history of a demyelinating disease, such as multiple sclerosis;

15. Have or have had an opportunistic infection (eg, herpes zoster [shingles],
cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening;

16. Have undergone any joint replacement surgery;

17. Have a chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg. bronchiectasis), sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer;

18. Be considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section on: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation Rules;

19. Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB;

20. Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic
area), or splenomegaly;

21. Currently have any known malignancy other than the condition being treated or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence;

22. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease;

23. Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access;

24. Use any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer;

25. Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).

26. Have a concomitant diagnosis or history of congestive heart failure (NYHA class III or IV);

27. Be women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion.