Can Triple Therapy Match Biologics For RA At Lower Cost?

Is triple therapy with conventional DMARDs more effective than biologics for rheumatoid arthritis (RA), and are biologics ultimately worth their higher cost? Two leading rheumatologists met for a “Great Debate” on this question at the 2013 annual meeting of the American College of Rheumatology (ACR) in San Diego.

Ronald van Vollenhoven, MD, PhD, of the Unit for Clinical Therapy Research in Inflammatory Diseases at the Karolinska University Hospital in Stockholm, Sweden contends that patients improve faster and to a greater degree with biologics. “The future is in starting with biologics and switching to conventional DMARDs to maintain a low disease state or remission, although the cost would initially be greater,” he said. “In ideal situation, if cost was no objective, we’d use biologicals more.”

But recent clinical trails show conclusively that patients initially treated to target (low disease activity or remission) with DMARD triple therapy have outcomes as good as those started or switched to biologics, countered James R. O’Dell, MD, chief of rheumatology at the University of Nebraska Medical Center in Omaha. “If you start with conventional triple DMARD therapy," he pointed out, "less than 15% of patients will need biologics, and those that eventually take biologics have radiographic outcomes as good, or better, than with biologics.".

Current guidelines do not recommend DMARD triple therapy of methotrexate (MTX), sulfasalazine, and hydroxychloroquine for newly diagnosed RA patients. However, researchers presenting new data from clinical trials from the Netherlands (O’Dell was a co-author) are enthusiastic about the positive results with triple therapy versus MTX monotherapy, independent of corticosteroids.

The randomized Rotterdam Early Arthritis Cohort (tREACH) trial split 281 patients into three induction therapy groups followed every three months to assess their progress at one year:

•    Triple DMARD therapy or MTX25 mg per week, 2 g sulfasalazine 2g per day, and 400 mg hydroxychloroquine daily (n=91);
•    The same triple DMARD therapy with tapered corticosteroids starting at15 mg a day (n=93);
•     MTX 25 mg per week with similarly tapered oral glucocorticoids (n=97).

Triple therapy shows better clinical effectiveness than MTX monotherapy, with 80% of patients reaching low disease activity. Triple therapy also reduces the burden of disease and treatment failure, with faster attainment and maintenance of treatment goals – all with 40% fewer prescriptions for biologics after a year, reported co-investigator Pascal de Jong PhD of the Erasmus Medical Center.

“We know that outcomes are better when you give therapy early and aggressively in early rheumatoid arthritis,” de Jong concluded. “If you start with biologicals it will cost more to control disease,” he added.

The same tREACH study also finds initial triple therapy more cost-effective than MTX monotherapy with lower direct (medical) costs and indirect costs to workers (e.g., less sick leave).

An analysis of the National Data Bank for Rheumatic Diseases does show a higher discontinue rate for triple therapy, which is not surprising when people have to take multiple pills, said Kaleb Michaud PhD of the University of Nebraska Medical Center and a co-author of the study.

While cost turns out not to be a major factor in patient discontinuation in this study, and biologicals may be overused, “you do have to recognize money is an issue,” conceded O’Dell. In the current health care climate, clinicians might well be mandated to try triple therapy before going to biologicals, he added.

In the end, however, all the investigators agreed that it boils down to an individual choice by patients and clinicians as to whether triple therapy or biologicals will provide the most benefits for the cost.

“It’s nice to have options,” concluded de Jong.