Aggressive versus step-up treatment approach for early rheumatoid arthritis

This clinical trial compared between different approaches for early rheumatoid arthritis treatment.

It is recommended for patients who were recently diagnosed with rheumatoid arthritis (RA) to start medical treatment as early as possible in order to reduce disease progression and long-term disability. But what is the best choice of initial therapy?

Disease-modifying anti-rheumatic drugs (DMARDs) are a group of medications commonly used for the treatment of RA. There are 2 main types of DMARDs: standard and biologic. Common standard DMARDs include methotrexate (MTX, Trexall, Rheumatrex), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). Etanercept (Enbrel) is a biologic DMARD that belongs to a class of drugs called tumor necrosis factor (TNF) inhibitors.

The traditional approach for management of patients newly diagnosed with RA is a “step-up” method that starts with MTX alone (monotherapy) and if the disease does not improve, add one or more standard or biologic DMARDs. A more aggressive, though less common, therapeutic approach is an immediate combination therapy with several DMARDs.  

This clinical trial compared the outcomes of different drug regimens for  patients with early RA without prior treatment, and followed their therapy consequences after 2 years.

The trial enrolled 755 adult patients who were recently diagnosed with RA. Patients were appointed randomly to 4 different groups:

Two immediate combination treatment groups – immediately started on either MTX plus etanercept or MTX plus sulfasalazine and hydroxychloroquine (triple therapy).

Two step-up from MTX monotherapy groups – received MTX monotherapy for 24 weeks and afterward were co-administered with either etanercept or sulfasalazine and hydroxychloroquine (triple therapy).

The researchers followed the patients for two years and evaluated their disease activity based on certain variables, i.e. improvement in signs and symptoms, physical disability and joint damage.

There were no differences in disease activity between patients who received MTX plus etanercept and those randomized to triple therapy, regardless of

whether they received immediate combination treatment or step-up from MTX monotherapy.

Immediate combination treatment with either strategy was more effective than the step-up approach after two years.

Treatment with the combination of MTX plus etanercept resulted in a statistically significant radiographic benefit compared with oral triple therapy.

In this trial (analyzing disease activity and joint damage after two years of treatment), patients newly diagnosed with RA, responded better to an initial aggressive drug therapy (with either triple DMARD therapy or MTX plus etanercept) compared to the step-up approach (beginning with MTX monotherapy).

MTX plus etanercept was superior to the triple therapy in terms of joint damage.