A double blind, randomised, placebo controlled, multicentre trial of Anti-Tumour Necrotising Factor alpha (Anti-TNFa) chimeric monoclonal antibody (infliximab, Remicade®) in combination with methotrexate in patients with very early inflammatory arthritis

Not Applicable

Completed

• Conditions: Arthritis; Early inflammatory arthritis; Musculoskeletal Diseases

• Registration Number: ISRCTN21272423
• Lead Sponsor: Medical University of Vienna (Austria)

Brief Summary

2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30092827

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-12-18
• Study Completion: 2013-10-07
• Last Update Posted: 3 September 2018

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

All patients to be included into this trial must meet the following inclusion criteria:
1. Men and women, between 18 and 75 years of age, capable of understanding and signing an informed consent
2. The presence of arthritis:
2.1. Must be established in a rheumatology centre
2.2. Must be present in at least two joints of the 66 joint count, of which at least one joint must be an Metacarpophalangeal- (MCP-), or a Proximal Interphalangeal- (PIP-) (Interphalangeal- [IP-]), or a wrist- or a Metatarsophalangeal- (MTP-) joint. Two MTP-joints will not suffice. Any kind of polyarthritis (= 6 joints of any kind) will be sufficient
2.3. Without any previous episodes of inflammatory joint disease
3. Duration of symptoms:
3.1. Must be reported by the subject and should involve the inflamed joints described under point 2
3.2. Must be 2 weeks at least
3.3. Must be 16 weeks at most, as reported by the subject, including the observation period of at least 2 weeks by the physician
4. Confirmation of persistent arthritis:
4.1. Duration must be 2 weeks at least
4.2. Duration must be 12 weeks at most
4.3. Must be documented by the same rheumatology centre that established arthritis at the first visit
4.4. 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 sterilisation) 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 the protocol)
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

Patients must not:
1. Have arthritis with a distinct diagnosis, made after a routine diagnostic work-up (examples are Systemic Lupus Erythematosus [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 greater than 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:
6.1. White Blood Cells (WBCs) less than 3.0 x 10^9 cells/L
6.2. Platelets less than 100 x 10^9 cells/L
6.3. Serum creatinine greater than 1.4 mg/dL
6.4. 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 Disease Modifying Anti-Rheumatic Drugs (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 C-antibodies
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 (e.g., 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 (e.g., 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 the protocol)
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 (e.g., 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, haematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease
23. Be unable or

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 two consecutive visits after month 3 during the first 54 weeks.