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CHICAGO -- The current mantra of hitting rheumatoid arthritis (RA) hard and early should not equate to starting patients on biologic therapies right out of the gate, a prominent RA specialist said here.

Conventional disease-modifying anti-rheumatic drugs (DMARDs), especially methotrexate, should still be the mainstays of RA treatment -- at the outset and as well as later on for those patients who do eventually require biologics, said James R. O'Dell, MD, of the University of Nebraska Medical Center in Omaha, at the .

And this advice is not just about biologics' cost -- it's based on the decades of clinical evidence showing that methotrexate is the equal of, and in some respects superior to, the newer medications.

One example, O'Dell offered: the that showed an intensive DMARD-based regimen achieved disease remission in 65% of patients with early RA.

And how about the comparing methotrexate to adalimumab (Humira) alone or a combination of both? Methotrexate was just as effective as the biologic as monotherapy -- with a dose O'Dell called "suboptimal" (less than 20 mg/week).

In fact, O'Dell said, "a biologic has never beaten methotrexate in a [head-to-head] trial like this."

Nevertheless, methotrexate is still underutilized in early RA while biologics are overused, he contended. He was senior author in a showing the following:

• One-quarter of patients received a biologic before methotrexate

• Among patients on methotrexate when biologics were added, the methotrexate dose was only 15 mg/week

• Subcutaneous methotrexate, which is effective in many patients not responding to the oral form, was tried in only 7% of patients who ultimately received a biologic

• And among those patients receiving the subcutaneous form, three-quarters did not need a biologic in the subsequent 5 years

It's true that methotrexate is contraindicated in some patients, especially women who may become pregnant or who are breastfeeding. Nevertheless, those legitimate cautions cannot account for the underuse of methotrexate in those data, he suggested.

In his talk here, O'Dell was particularly insistent that subcutaneous methotrexate be tried when patients don't respond adequately to maximal oral dosing. Interindividual variation in oral bioavailability is considerable, he said, and the switch often benefits patients with gastrointestinal intolerance of oral dosing.

He also emphasized that patients should remain on methotrexate for as long as treatment continues, unless it's absolutely contraindicated or cannot be tolerated in any form. Its efficacy is additive with most other drugs studied, including all the conventional DMARDs, all tumor necrosis factor (TNF) inhibitors, and rituximab. (It remains unclear whether the same is true for the interleukin-6 inhibitor tocilizumab [Actemra] or the JAK inhibitors, he said.)

For those patients who cannot have methotrexate, O'Dell went over the options; hydroxychloroquine or azathioprine for the breastfeeding patient, for example, and leflunomide for those with severe kidney disease.

O'Dell also noted that these alternative agents have their own contraindications: JAK inhibitors aren't suitable for patients at high risk for zoster infections, and minocycline should be avoided in patients for whom hyperpigmentation is unacceptable.

The overarching point is that patients need to be treated individually -- including those who don't want methotrexate for lifestyle reasons. (It requires monitoring and some patients "don't want labs," he said.)

Fortunately, the RA clinician has a big toolbox that holds something for nearly every patient.