Initial therapy with methotrexate (MTX) plus doxycycline is more effective than MTX alone among patients with early seropositive rheumatoid arthritis (RA), according to a new study in the February issue of Arthritis & Rheumatism.1

In the 2-year double-blind randomized controlled trial, 66 patients with seropositive RA of <1 year duration who had not been previously treated with disease-modifying antirheumatic drugs (DMARDs) were randomized to one of three groups: 100 mg of doxycycline twice daily with MTX (high-dose doxycycline group); 20 mg of doxycycline twice daily with MTX (low-dose doxycycline group); or placebo with MTX (placebo group). Treatment was started with an MTX dosage of 7.5 mg/week and titrated every 3 months until patients achieved remission or attained the maximum dosage of 17.5 mg/week. The primary endpoint was an American College of Rheumatology 50% improvement (ACR50) response at 2 years.

At 2 years, 41.6% of patients in the high-dose doxycycline group achieved ACR50, as did 38.9% of those in the low-dose doxycycline group and 12.5% of patients in the placebo group. Four patients in the high-dose doxycycline group, two patients in the low-dose doxycycline group, and two patients in the placebo group withdrew due to toxic reactions.

"The therapeutic responses to low-dose and high-dose doxycycline were similar, suggesting that the antimetalloproteinase effects were more important than the antibacterial effects," conclude the researchers, led by James R. O'Dell, MD, chief of rheumatology at the University of Nebraska Medical Center in Omaha, Nebraska. "Further studies to evaluate the mechanism of action of tetracyclines in RA are indicated."

Antimetalloproteinase effects cited

"The groups that got doxycycline plus MTX did significantly better," says Dr. O'Dell. "The proviso is that we don't believe any of these effects have to do with treating infection [because] the tetracycline class of antibiotics have significant other effects in terms of regulating the immune system and inhibiting metalloproteinases that we believe are more responsible for the mechanism of action."

When asked what role doxycycline may have in the treatment of RA if further studies confirm and support these findings, Dr. O'Dell tells CIAOMed that "if we have therapies that are cheaper and have efficacy, they may be something to consider in places where people are looking hard at costs." Going forward, he says, head-to-head comparisons in early seropositive RA are warranted.

"There is a role for adding doxycycline to DMARDs such as MTX, but I would not use it alone," comments Jessica R. Berman, MD, a rheumatologist at the Hospital for Special Surgery in New York City. "Because of the antimetalloproteinase effects, it may decrease inflammation, but I think the effect is probably similar to adding a nonsteroidal," she says, adding that she rarely uses it.

Reference

  1. O'Dell JR, Elliot JR, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: Doxycycline plus methotrexate versus methotrexate alone. Arthritis Rheum. 2006; 54:621-627.