Methotrexate is known to be effective as a disease-modifying antirheumatic drug (DMARD), but several studies in recent years have shown that a methotrexate combination with another drug makes it even more effective.

Arava. In a study of 263 patients, those taking both methotrexate and Arava (leflunomide) were more than twice as likely to experience improvements in joint problems, pain and ability to function than those taking methotrexate with placebo.

Enbrel. In a study of 682 people with rheumatoid arthritis, a combination of methotrexate and Enbrel (etanercept) provided a better response than either drug alone. After 52 weeks, 85 percent of patients on the combo had achieved at least a 20-percent improvement compared to 76 percent with Enbrel alone and 75 percent with methotrexate alone.

Humira. Of 60 RA patients who were not responding well to methotrexate, 40 of 45 patients taking both Humira (adalimumab) and methotrexate achieved at least a 20-percent improvement within four weeks; some within 24 hours. Only four patients receiving methotrexate and placebo improved in that time.

Kineret. In a study of 419 people, 46 percent of patients taking Kineret (anakinra) with methotrexate showed at least a 20-percent improvement in joint counts, pain, function and erythrocyte sedimentation rate; only 19 percent of those taking methotrexate with placebo improved.

Orencia. A study of 638 patients in whom rheumatoid arthritis was not well controlled by methotrexate showed that methotrexate plus Orencia (abatacept) was more effective at easing RA symptoms than was methotrexate alone. At 12 months, 29 percent of those given the combination had achieved at least a 70-percent reduction in pain and stiffness compared to six percent of those given methotrexate only. Two additional studies showed the methotrexate/Orencia combo also reduced structural damage.

Remicade. A study of 1,049 people with recently diagnosed rheumatoid arthritis showed that a methotrexate combination with Remicade (infliximab) was superior to methotrexate alone in preventing progression of joint destruction, reducing disability and increasing clinical improvement. Six months into the trial, patients treated with only methotrexate already had significantly more joint damage than was evident in X-rays of people taking both methotrexate and Remicade.

Rituxan. In a study of 517 patients with active RA, 51 percent of those given Rituxan (rituximab) with methotrexate had achieved at least a 20-percent reduction in pain and stiffness within six months of starting treatment, compared to 18 percent of those receiving methotrexate alone. Twelve percent had achieved a 70-percent reduction, compared to only one percent of those receiving methotrexate alone.