IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease;A randomized clinical trial in patients with recent-onset arthritis to compare the efficacy of DMARD combination therapy including prednisone with combination therapy including adalimumab, a TNF-blocking agent.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 610

Inclusion Criteria

1. minimum age of 18 years
2. at least one swollen joint
3. at least one other painful joint
4. symptom duration shorter than 2 years
5. diagnosis rheumatoid arthritis according to the ACR classification criteria or
6. diagnosis undifferentiated arthritis, suspected for rheumatoid arthritis by the rheumatologist, as no classification criteria exist.
7. patients naive for treatment with corticosteroids or disease modifying anti-rheumatic drugs (DMARDs).

Exclusion Criteria

1. previous therapy with DMARDs or with corticosteroids (exception: one dose of parenteral corticosteroids within the last 6 months, but not within the last 2 months, or an oral dose of prednisone of =<10 mg/day for =< 2 weeks within the same period allowed).
2. pregnancy or wish to become pregnant during the study, or childbearing potential without adequate contraception
3. concomitant treatment with another experimental drug
4. history or presence of malignancy within the last five years
5. bone marrow hypoplasia
6. elevated hepatic enzyme levels (ASAT, ALAT > 3 times normal value)
7. serum creatinine level > 150 umol/l or estimated creatinine clearance of < 75%
8. uncontrolled diabetes mellitus (according to the rheumatologist)
9. uncontrolled hypertension or moderate to severe heart failure (NYHA class III/IV)
10. alcohol or drug abuse
11. history of infected joint prothesis within the previous 3 months
12. serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months
13. chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis
14. history of active tuberculosis requiring treatment within previous 3 years, or signs and symptoms of latent infection with tuberculosis, based on medical history, physical examination, tuberculin (PPD) skin test or chest radiograph (see 9.3.1).
15. history of other granulomatous infections as histoplasmosis or coccidiomycosis
16. evidence of active cytomegalovirus, active pneumocystis carinii, active aspergillosis, or drug resistant atypical mycobacterium infection
17. history of opportunistic infections such as herpes zoster within previous 2 months.
18. history of active hepatitis B infection or evidence of a latent infection (see 9.3.1).
19. documented HIV infection, AIDS related complex (ARC) or AIDS.
20. history of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease.
21. Multiple sclerosis or neurological symptoms suspect for demyelinising disease.
22. Hypersensitivity to human immunoglobuline or other constituents of adalimumab

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. The percentage of patients achieving remission after 4 months and after 1<br /><br>year of combination therapy, defined as a DAS < 1.6<br /><br>After 4 months: with the combination therapy methotrexate and prednisone<br /><br>After 1 year: after randomization into the combination therapy with either<br /><br>prednisone or adalimumab.<br /><br><br /><br>2. Functional capacity, measured by the health assessment questionaire (HAQ)<br /><br>after 1 year<br /><br><br /><br>3. Radiological joint damage: absolute and progression from baseline, measured<br /><br>by the modified Sharp/van der Heijde score. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- MACTAR questionnaire<br /><br>- Short Form 36 questionnaire<br /><br>- EuroQol questionnaire<br /><br>- Time Trade Off technique<br /><br>- costs<br /><br><br /><br>- ACR painful and swollen joint count<br /><br>- Patient measures, via visual analog scale (VAS)<br /><br>pain, morning stiffness, disease activity, general health<br /><br><br /><br>- laboratory measurements: chemical (kidney and liver function), hematological<br /><br>(leucocytes, thrombocytes, hemoglobine), parameters of inflammation (C-reactive<br /><br>protein, erythrocyte sedimentation rate), bone markers, genetic factors</p><br>

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