Very early inflammatory arthritis.
Conditions
Interventions
200 subjects (80 per DMARD treatment arm and 40 in the supportive treatment arm) will be randomly assigned, stratified by glucocorticoid use to one of the following treatment groups:
Group I:
To rec
Sponsors
Josef S. Smolen MD
Department of Rheumatology
Medical University of Vienna
Waehringer Guertel 18-20
A-1090 Vienna, Austria
+43-1-40400-4300
josef.smolen@wienkav.at
Eligibility
Inclusion criteria
Inclusion criteria: 1. Men and women, >= 18 and = 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.
Exclusion criteria
Exclusion criteria: 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) 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of presence of clinical remission between treatment with infliximab plus MTX versus MTX monotherapy and supportive treatment only at end of infliximab therapy, i.e. at at least 2 consecutive visits after month 3 during the first 54 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Comparison, Group I versus Group II and Group III of: 1. the presence of persistent clinical remission at week 106; 2. the presence of persistent clinical remission at week 54 since start of therapy; 3. the presence of persistent clinical remission at week 106; 4. radiographic progression at week 22, 54 and 106; 5. the presence of clinical remission at every time point during the trial; 6. the presence of clinical remission by SDAI and CDAI at every time point during the trial; 7. the presence of remission by Pinals criteria at every time point during the trial; 8. the presence of near-remission (DAS28 < 2.6) at every time point during the trial; 9. the duration of clinical remission or near-clinical remission during the entire trial; 10. time to remission; 11. time to relapse after withdrawal of infliximab therapy in patients who achieved persistent clinical remission; 12. all variables included in the WHO/ILAR core set for clinical trials (66-joints swollen joint count, 68-joints tender joint count, pain, patient and evaluator global assessments, health assessment questionnaire (HAQ), CRP, ESR) at every time point during the trial; 13. DAS28, SDAI, CDAI and RADAI at every time point during the trial; 14. ACR 50 and 70 response, SF36, Fatigue (VAS) and Pharmacoeconomics at week 2, 6, 14, 22, 30, 38, 54, 70 and 106; 15. glucocorticoid and NSAID/coxib dosage at every time point during the trial; 16. number of visits at which relapse from remission was noted. | — |
Contacts
Public ContactTanja A. Stamm
Department of Rheumatology Medical University of Vienna Waehringer Guertel 18-20
Outcome results
None listed