Methotrexate alone works just as well as combination treatments for early rheumatoid arthritis (RA) even in patients with “poor prognosis” features, according to a new study published online in the journal Arthritis & Rheumatism. With so many new drugs available now for treating RA, this finding adds a piece of information to the puzzle of which drug (or combination of drugs) should be given to which patients and at what point in the course of the disease.

Many recent studies have shown that treating RA aggressively in the early stages improve the odds of a patient achieving remission. What is not clear is, for how long is this “window of opportunity” for remission open.

"We now have very good data that patients are not in any way worse off because they were given a therapeutic trial of methotrexate alone before they were stepped up [to additional medications]," says lead author James R. O’Dell, MD, chief of rheumatology in the Division of Rheumatology & Immunology at the University of Nebraska Medical Center in Omaha.

Methotrexate – a disease-modifying antirheumatic drug (DMARD), which slows the progression of the disease – is considered to be “the cornerstone of successful therapy for the treatment of rheumatoid arthritis,” according to the study authors.  It can be used alone, with other DMARDs or with a biologic, such as adalimumab (Humira), etanercept (Enbrel) or abatacept (Orencia).

"Most clinicians start patients on methotrexate. But there is a subset that believes they need multiple drugs out of the gate. This speaks to those and says, ‘You don't need to do that,’” says Dr. O’Dell.

But even the American College of Rheumatology (ACR) recommends starting with methotrexate alone – except when there are “poor prognosis” features, which include being positive for rheumatoid factor (RF), being positive for anti-cyclic citrullinated peptide antibodies or having bone erosions visible on X-rays.  In those cases, the recommendation from ACR is to use more powerful combination therapies, including methotrexate plus a biologic or so-called “double” or “triple” therapy (methotrexate plus sulfasalazine and/or hydroxychloroquine).

But more intensive treatments often cost more – especially in the case of biologics – and carry a greater risk of side effects.

Dr. O’Dell says the key question he and his colleagues wanted to answer was: If you give patients with early, aggressive disease methotrexate alone to start with, and then find that it is not enough and you have to step up to more powerful therapies, has the patient lost anything compared to someone who got the more powerful combination in the first place?

To find out, they conducted an analysis of patients from the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial, a randomized double-blind study that followed 755 patients with early, poor prognosis RA for two years. The first findings of the TEAR trial were published last year and concluded, among other things, that the older triple therapy appears to be equally as effective as the newer biologic drugs for achieving good control of RA.