Drug Combos Effective Against Rheumatoid Arthritis

MONDAY Nov. 26, 2007 -- Combining an older synthetic drug with a newer, "biologic" medication may work best to ease the joint swelling and tenderness of rheumatoid arthritis, a new study finds.

There are many therapies for rheumatoid arthritis, but the newer drugs are not better than older ones when used alone, the report's authors found.

"There are no clinically important differences among the older synthetic drugs or among the newer biologic drugs," said lead researcher Dr. Katrina E. Donahue, an assistant professor in the department of family medicine at the University of North Carolina, Chapel Hill. "There are combination therapies that do work better than using one drug in people not responding to one drug alone," she said.

Combining a synthetic with a biologic appears to work best, Donahue said. However, which combinations are most effective still isn't clear. In addition, the short-term side effects appear to be the same for both types of drugs, she added.

In the study, Donahue's team reviewed 23 published studies that compared the benefits and harms of different rheumatoid arthritis drugs. These included, synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

Synthetic DMARDs include hydroxychloroquine (Plaquenil), leflunomide (Arava), methotrexate (Trexall) and sulfasalazine (Azulfidine). Biologic DMARDs include abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), etanercept (Enbrel), infliximab (Remicade) and rituximab (Rituxan). Corticosteroids include drugs such as prednisone.

Donahue's group found that combining methotrexate with a biologic DMARD worked better than methotrexate or a biologic alone. They also found that methotrexate was as effective as the biologics adalimumab and etanercept in early rheumatoid arthritis.

Adalimumab and etanercept had better short-term results. However, biologics and methotrexate boost the risk of serious infection, including a reoccurrence of tuberculosis, the researchers found.

Donahue's team also found that prednisone, along with hydroxychloroquine, methotrexate or sulfasalazine worked better in reducing joint swelling and tenderness than using a synthetic DMARD alone.

There was no difference in effectiveness between the synthetic DMARDs methotrexate, leflunomide and sulfasalazine. And combining methotrexate and sulfasalazine was no more effective than using either one of the drugs alone.

There was also not enough evidence to say whether combining two biologics was more effective than using one biologic, Donahue said. For every 1,000 people taking a biologic for three to 12 months, 17 have a serious infection and combining two biologics can increase that risk, the researchers noted.

In addition, rates of painful injection site reactions are more common for anakinra (67 percent) than for etanercept (22 percent) or adalimumab (18 percent), Donahue's group found.

Donahue recommended that patients talk to their doctors about developing a treatment plan that is tailored to their individual condition. "Rheumatoid arthritis is very patient-specific -- there are many therapies, and there doesn't appear to be one therapy that is clearly superior," she said. "It's a conversation between you and your rheumatologist about what might be right for you."

One expert said the study will be useful for physicians.

"This is a great summary about what we know about how DMARDs work," said Dr. Steven Vlad, a fellow in rheumatology at Boston University Medical Center. "That basic finding -- that one synthetic of biologic doesn't work any better than others -- is a good thing to remind ourselves of," he said.

Some doctors think that biologics work better, Vlad said. "But that's not the case. All these drugs seem to work equally as well," he said.

Combination therapy can be effective, Vlad said, but biologics should be the last choice. "Methotrexate is what most doctors are going to go with first," he said. "You start with methotrexate. If that doesn't work, you add another synthetic drug; if that doesn't work, maybe then you go to a biologic," he said.

More information

For more on rheumatoid arthritis, visit the Arthritis Foundation.

Posted: November 2007


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