Study: Symptoms, Not Prognosis, Should Guide Early RA Treatment


Is it too soon for personalized medicine in early RA treatment? Dutch investigators think so, as they advocate for treatment strategies that are not based on patient prognosis.

Markusse IM, de Vries-Bouwstra JK, Huub Han K, et al., Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis. Arthritis Research & Therapy (2014) 16:430  doi:10.1186/s13075-014-0430-3. (Published: September 25, 2014)

Patients with early rheumatoid arthritis (RA) do well on combination therapy even if they have a poor prognostic profile, according to Dutch researchers.

Their post hoc analysis of a large clinical trial found that tailoring early RA treatment based on risk stratification – as advocated by the European League Against Rheumatism (EULAR) – did not appear to be effective.

Instead, the study authors  advocate a treatment strategy  based on rapid symptom relief rather than on prognostic factors.

According to EULAR, RA patients with a poor prognosis have the most to gain from initial combination therapy versus patients at lower risk.

However, data for the 508 RA patients in the current study showed good outcomes with initial combination therapy compared with monotherapy, regardless of patients’ risk profiles. The original clinical trial had randomized them to methotrexate (MTX) monotherapy (stable dose or step-up), or to combination therapy (MTX, sulfasalazine, and prednisone or MTX plus infliximab).

Baseline characteristics predictive of poor prognosis included the presence of rheumatoid factor and anti-citrullinated peptide autoantibodies, high inflammation (elevated C-reactive protein), and greater radiographic joint damage.

Of the 508 participants, 192 had a poor prognosis, and they tended to be slightly younger (ages 60-68 versus ages 72-78), with higher autoantibody titers and more erosive disease.

More than 70% of all patients achieved American College of Rheumatology 20% response criteria (ACR20) with initial combination therapy after 3 months, compared to 38% of those on monotherapy.

Regardless of their status as poor or “non-poor prognosis,” more patients on initial combination therapy versus monotherapy achieved:

•   ACR50 and ACR70 responses,

•   Remission according to disease activity in 28 joints score (DAS28 1.6 or below),

•   Better functional ability in the form of lower scores on the Health Assessment Questionnaire at 3 months.

Combination therapy also led to less radiographic progression (lower Sharp van der Heijde Scores). Combination therapy-based toxicity rates were similar in all patients.

The differences between the two treatment groups held up at 1 year in terms of ACR20, ACR50, and radiographic progression.

Although EULAR no longer supports the idea  that patients with the worst prognosis gain more from early intensive treatment, its 2013 revised recommendations state that “risk stratification is an important aspect of the therapeutic approach to RA.”

But given the similar responses among patients in this study, such personalized medicine for early RA is “not yet feasible” and “the choice of treatment strategy should depend more on rapid relief of symptoms than on prognostic factors,” according to the authors.

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