Combining medications often best strategy to battle rheumatoid arthritis

For patients with rheumatoid arthritis, combining one well-known, lower cost synthetic drug with one of six biologic medications often works best to reduce joint swelling or tenderness, according to a new report funded by the Agency for Healthcare Research and Quality, part of the U.S. Department of Health and Human Services.

Researchers reviewed published evidence to compare the benefits and harms of three classes of medications: synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids. Synthetic DMARDs include hydroxychloroquine, leflunomide, methotrexate and sulfasalazine; biologic DMARDs include abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab; and corticosteroids include drugs such as prednisone.

The report concluded that combining methotrexate, a synthetic DMARD, with one of the biologic DMARDs works better than using methotrexate or a biologic DMARD alone. The report also found that methotrexate works as effectively as the biologic DMARDs adalimumab and etanercept for patients who have early rheumatoid arthritis. Adalimumab and etanercept, however, show better short-term results as measured by X-rays of joints. The report also emphasized that biologic DMARDs and methotrexate increase the risk of serious infection, including a reoccurrence of tuberculosis.

“Rheumatoid arthritis is a painful, degenerative disease that affects people of all ages and can profoundly impact quality of life,” said AHRQ Director Carolyn M. Clancy, M.D. “This report establishes a clear, unbiased summary of what is known about current treatments. It also identifies areas where more research is needed.”

About 2 million Americans have rheumatoid arthritis, a long-term illness that causes joint and tissue inflammation. Rheumatoid arthritis is an autoimmune disease, meaning that the body confuses healthy tissue for foreign substances and attacks itself. The cause is unknown. The disease often begins with fatigue, morning stiffness, weakness and muscle aches. Eventually, joint pain appears. Pain may affect the wrists, knees, elbows, fingers, toes, ankles or neck. Other symptoms may include anemia, eye burning, limited range of motion, skin redness and swollen glands. Joint destruction may occur within 1 to 2 years after the disease appears. Some cases cause deformities. Treatment typically begins with medications but may include physical therapy and surgery.

Among other findings in the report:

• Combining prednisone with the synthetic DMARD hydroxychloroquine, methotrexate or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function.
• No meaningful clinical differences can be found between methotrexate and either leflunomide or sulfasalazine.
• Combining the synthetic DMARDs methotrexate and sulfasalazine is no more effective than using just one of the medications for patients with early rheumatoid arthritis.
• Not enough evidence exists to determine whether combining two biologic DMARDs is more effective than using one biologic DMARD.
• About 17 of every 1,000 people taking a biologic DMARD for 3 to 12 months have a serious infection. Combining two biologic DMARDs can increase the risk.
• Among biologic DMARDs, rates of painful injection site reactions are more common for anakinra (67 percent) than for etanercept (22 percent) or adalimumab (18 percent).
• More long-term research is needed on rheumatoid arthritis medications, including how the outcomes of these drugs vary among patients with different health conditions and demographic characteristics. More comparative studies on various combinations of drugs are critical. Also important is investigating whether taking the medications earlier (especially biologic DMARDs) is better for long-term outcomes.