Dose-to-target of etanercept treatment: a dose-tapering randomized controlled trial in patients with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis.

The proportion of patients with rheumatic diseases treated with biologics has
increased considerably over the last decade. As a consequence, the financial
burden for the health care system has increased enormously. Therefore, dose
reduction of biologics is currently a hot topic in rheumatology practice.
However, there is limited information about the success rate of dose tapering
or discontinuation as well as predictors of success and the risks of dose
reduction, like deterioration of disease activity and radiographic progression.
Recently, a few studies in rheumatoid arthritis (RA), psoriatic arthritis (PsA)
and ankylosing spondylitis (AS) patients on biologics were published but these
studies have some major limitations: limited numbers of patients, different
criteria for inclusion and remission and flare were used, in some only
retrospective data was available.

To determine the proportion of patients with RA, AS or PsA maintaining minimal
disease activity (MDA) after dose interval prolongation of etanercept.
Secondary objectives: To study the cost-effectiveness of tapering down
etanercept treatment, to investigate whether the lowest effective etanercept
dose will reduce the risk of adverse events and to study the predictive value
of serum etanercept trough levels for successful down titration.

Open randomized controlled study of a dose-to-target step-down treatment
strategy of etanercept which consists of 2 phases, including 150 rheumatoid
arthritis, 50 psoriatic arthritis and 50 ankylosing spondylitis patients.

Intervention: Patients with Minimal Disease Activity who are treated with
etanercept for at least 6 months will be randomly assigned to continuation of
etanercept every week or prolongation of the dosage interval to once every 2
weeks (phase 1). Patients will be followed for 6 months. Thereafter, the second
phase of this study starts, in which patients, who are still in a state of
minimal disease activity, will be further down-titrated to either etanercept 50
mg every two weeks (continuation group first phase) or discontinuation of
etanercept. Patients will be followed for an additional 12 months.

Phase 1: Patients with low disease activity will be randomly assigned to
continuation of etanercept 50 mg per week or etanercept 50 mg per two weeks.
Patietns will be followed for 6 months.
Phase 2: Patientens who remained in a state of low disease activity with
etanercept 50 mg per two weeks will stop with etanercept. Patients who were
still on standaard treatment and who are in a state of low disease activity
will continue with etanerceot 50 mg per two weeks. Patientes will be followed
for 12 months.

Nature and extent of the burden: We hypothesize that patients with Minimal
Disease Activity will remain in a state of Minimal Disease Activity after dose
interval prolongation of etanercept, however, an increased disease activity
risk can not be excluded, especially in patients discontinuing etanercept.