COBRA-light study, an open randomised trial comparing a modified COBRA therapy with the COBRA therapy according to BeSt in early rheumatoid arthritis.

Early treatment of rheumatoid arthritis is important to lower disease activity
and suppress radiologic progression. (*window of opportunity*)
Combination therapy is proven to be superior to monotherapy in the treatment of
early RA. The COBRA therapy is effective in several trials, and the positive
effect on radiologic progression sustained over time.
In a recent trial (BeSt) comparing different treatment strategies the COBRA
therapy and initial therapy with Infliximab (a TNF-blocker) were equally
effective in improving functional ability and preventing radiographic damage.
Apparently most rheumatologists and or patients have resistance in prescribing
this therapy. This is because of the possible side effects, the combination of
MTX and sulfasalazine, the low dose MTX and the complexity of the medication.
For this reason several rheumatologists treat their patients with different
combinations of prednisone (usually lower then the 60mg used in the original
COBRA-schedule) and different dosages of MTX.
It is obvious that it is a step forward if we could demonstrate that the
proposed COBRA-light is as effective as the original COBRA-schedule according
to BeSt.

Are there differences is efficacy, side effects, tolerance en costs in patients
with early RA in treatment with COBRA-light compared with COBRA according to
BeSt?

Open, randomised trial comparing the efficacy, side effects, tolerance en costs
of COBRA-light in patients with early RA in treatment with COBRA according to
BeSt.
In the first year patients will be seen frequently in order to follow
disease-activity, side effects and cardiovascular parameters. In the first year
patients will be seen at 2, 4, 8, 13, 26, 39 en 52 weeks. In the follow-up
period of the second year patients will be seen every six months.

COBRA light:

Week 1: Pred 30mg
Week 2: Pred 20mg MTX 10mg
Week 3: Pred 15mg MTX 10mg
Week 4: Pred 10mg MTX 10mg
Week 5: Pred 10mg MTX 17,5mg
Week 6: Pred 10mg MTX 17,5mg
Week 7: Pred 10mg MTX 17,5mg
Week 8: Pred 10mg MTX 17,5mg
Va wk 9:Pred 7,5mg MTX 25mg

COBRA BeSt:

Week 1: Pred 60mg
Week 2: Pred 40mg MTX 7.5mg SSZ 500
Week 3: Pred 25mg MTX 7.5mg SSZ 1000
Week 4: Pred 20mg MTX 7.5mg SSZ 1500
Week 5: Pred 15mg MTX 7.5mg SSZ 2000
Week 6: Pred 10mg MTX 7.5mg SSZ 2000
Va wk 7: Pred 7,5mg MTX 7.5mg SSZ 2000

At 13, 26, 39, 52, 78 en 104 weeks the disease activity will be measured. If
the disease activity measured by DAS(44) is > 1,6 the medication needs to be
adjusted. DAS(44)<1,6 is regarded al clinical remission: no change of therapy.
All patients will receive folic acid 5 mg/day.

Normal risks.
The total radiation of the X-rays meets the requirements as obtained in The
Netherlands.