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Use of TNF-blocking Therapy in Combination With DMARDs in Patients With Early Rheumatoid Arthritis

Phase 4
18 Years
60 Years
Open (Enrolling)
Rheumatoid Arthritis

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Trial Information

Use of TNF-blocking Therapy in Combination With DMARDs in Patients With Early Rheumatoid Arthritis

We want to study, whether early treatment with infliximab for 6 months started parallel with
the combination therapy of methotrexate, sulphasalazine, hydroxychloroquine and prednisolone
(COMBI) can induce quick remission in patients with early RA, if the remission can be
sustained after 6 months on patients continuing the COMBI treatment and can diminish the
risk of progression of erosive changes in patients with early RA, and if we can reduce costs
of the 2 treatment arms with respect to costs due to the disease.

100 patients with early RA will be included in the study. The patients are randomised into
COMBI + placebo or into COMBI +infliximab.

All patients are treated openly with COMBI, starting with a combination of methotrexate,
sulfasalazine, hydroxychloroquine and prednisolone. In addition, the patients are randomized
into a) infliximab or b) similar placebo. The COMBI treatment will be continued for 2 years,
but the infliximab/placebo will be given only during the first 6 months.

The patients will be evaluated clinically at week 0, 4, 6, 10, 14, 18, 22 and 26 (at the day
of infusion, prior to the infusion) and at months 8, 10, 12, 15, 18, 21, and 24 and at
annually thereafter till 10 years.

If a patient has adverse events due to individual drugs in the COMBI, the treatment can be
substituted by another DMARD.The disease activity will be measured according to the ACR core
set of disease activity.

Radiology of hands (PA projection) and feet (PA projection) at baseline and at 1, 2, 3, 4,
5, 7 and 10 years. We also will record sick leaves, loss of income, and work disability.

Inclusion Criteria:

- Diagnosis of RA fulfilling the ACR classification criteria for RA

- Patients within age group of 18-60 years

- Patients not permanently work disabled or retired

- Duration of symptoms < 12 months, and who have not received DMARD previously

- Patients with active disease (see below)

- Criteria for active disease at entry:

- > 6 swollen joints (66 joint count)

- > 6 tender joints (68 joint count)

- duration of early morning stiffness > 45 min and/or ESR > 30 mm/h and/or CRP >
20 mg/l

Exclusion Criteria:

- Previous treatment with DMARDs

- Previous treatment with oral glucocorticoids during the previous 6 months

- Less than 30 days from previous intra-articular injection with corticosteroids

- Allergy to sulphonamides

- Allergy to acetylsalicylic acid

- Allergy to methotrexate

- Allergy to antimalarials

- Previous treatment with biologicals

- Serum creatinine value > upper limit of normal (registered in 2 different blood

- Serum transaminase levels > 2x upper limit of normal (registered in 2 different

- Known/previous malignancy excluding basalioma or in situ cervical cancer >5 years

- Cardiac failure (NYHA III-IV)

- Previous history of tuberculosis and/or exposition to tuberculosis and/or typical
changes of previous/active tuberculosis in chest radiology

- Active infection

- Pregnancy

- Leukopenia (WBC < 4 x 109/l)

- Thrombocytopenia (platelets < 100 x 109/l)

- Active peptic ulcer

- Type I or type II diabetes under poor control

- Heavy use of alcohol

- Fertile women not practising contraception or who are planning pregnancy

- Male patients wishing to have children during the therapy

- Other autoimmune rheumatic disease

- Other chronic disease which judged by the physician could influence the patient's
compliance or intervene the study course

- Patient is not cooperative

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Remission by ACR criteria

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Marjatta Leirisalo-Repo, MD, Prof

Investigator Role:

Study Director

Investigator Affiliation:

Helsinki University


Finland: Finnish Medicines Agency

Study ID:




Start Date:

March 2003

Completion Date:

December 2015

Related Keywords:

  • Rheumatoid Arthritis
  • rheumatoid arthritis
  • methotrexate
  • sulfasalazine
  • hydroxychloroquine
  • infliximab
  • Arthritis
  • Arthritis, Rheumatoid