Clinical trial NCT00480272: Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
Official title: A Phase IV Multicenter, Randomized, Double-blind Study. prospeCtive Study on Intensive Early Rheumatoid Arthritis Treatment With adalimUmab: Induction of REmission and Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
clinical remission
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2007-05-30
Enrollment: 251
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypothesis: Early intensive treatment with anti-TNF agent plus methotrexate plus high dose prednisone may increase remission rate and may induce stable remission in Rheumatoid Arthritis Objective: to evaluate induction of remission using adalimumab, prednisone and methotrexate and maintenance of remission after discontinuation of adalimumab and prednisone

Detailed description: Treatment group A 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + prednisone 50 mg/d tapered to 6.25 mg 6 - 12 months: Adalimumab 40 mg eow plus methotrexate 20 mg weekly group B 0 - 6 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly + placebo 6 - 12 months: Adalimumab 40 mg eow + methotrexate rapidly titrated to 20 mg weekly

Follow up period - Open Label phase:

Patients achieving clinical remission will be than treated only with MTX and observed for another 12 months period. Patients who do not achieve clinical remission or patients who will experience a relapse of the disease will be treated according to standard of care (SOC) modalities.

Eligibility criteria: Inclusion Criteria:

* Active rheumatoid arthritis diagnosed for at least 6 weeks, but no more than 1 year, according to the revised 1987 ACR criteria
* Naïve to treatment with MTX
* Swollen joint count (SJC) \> 8 tender joint count (TJC) \> 8
* At screening CRP \> 1.5 mg/dL (15 mg/L) or ESR ≥ 28 mm/h
* ≥ 1 joint erosion or RF positivity or anti-CCP positivity
* Age 18-70 years.

Exclusion Criteria:

* Rheumatic autoimmune disease other than RA
* Functional class IV
* Any surgical procedure within 12 weeks prior to baseline or planned during the study.
* Pregnancy or breast feeding.
* Evidence of significant concomitant disease
* Primary or secondary immunodeficiency
* active infection of any kind
* History of previously untreated infection with mycobacterium tuberculosis or current treatment for same.
* History of cancer
* Any history or presence of congestive heart failure (CHF) (New York Heart Association classification for CHF: Class III or IV).
* Any history of myocardial infarction within 5 years.
* History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of adalimumab or methotrexate.
* Positive serology for hepatitis B or C indicating active infection.
* Hemoglobin \< 8.0 g/dL.
* Absolute neutrophil count (ANC) \< 1.5 x 103/L.
* Liver function abnormality

Primary outcomes:
measure: to evaluate the proportion of subjects who achieve remission at week 52 after treatment, as defined by DAS 28 </= 2.6
timeFrame: 52 weeks
Secondary outcomes:
measure: subjects who maintain stable remission at 24 months; ACR 20,50,70 at month 4,8,12,24; DAS 28 at month 4,8,12,24; HAQ at week 0,4,8,12,24; radiographic progression at months 12, 24; safety of different treatment regimens
timeFrame: 24 months
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: IRCCS S. Matteo Hospital
Study officials:
affiliation: IRCCS S. Matteo Foundation, Pavia
name: carlomaurizio montecucco, MD
role: PRINCIPAL_INVESTIGATOR
References: