Methotrexate works best in those patients with rheumatoid arthritis who are not taking high doses of prednisone, are older and do not have a very active form of the disease, researchers say.

Clinical trials have shown that methotrexate, the active ingredient in Rheumatrex, Trexall, Otrexup and Rasuvo, can help many RA patients. But some patients get more relief than others, while some experience more side effects.

“Patients outside clinical trials could be more complex and heterogeneous, with a wide range of comorbidities and clinical characteristics,” write the researchers from multiple hospitals in Argentina.

To find out which patients benefit most from the drug in “real life,” the researchers followed 384 patients who were taking methotrexate after never taking any methotrexate before, or any other drug in its class (disease-modifying antirheumatic drugs or DMARDs).

The average patient was 50 years old and had RA for 6.6 months. Eighty-three percent were female.

The doctors gave 349 patients a combination of prednisone and methotrexate. Of these, 208 took less than 10 mg per day of prednisone, 131 took 10-20 mg, and 10 took more than 20 mg.

The average dose of methotrexate was 16 mg per week, but 48% got doses of more than 20 mg per week.

Why Patients Switched Treatment

On average the researchers followed the patients for two years. During this time, 150 patients (39%) changed their treatment plan because methotrexate was not working well enough for them.

Out of these patients, seventy-nine percent added or substituted another DMARD. Another 7 percent changed because of a side effect. An additional 7 percent changed based simply on the patient’s preference. The final 7 percent changed for miscellaneous other reasons.

The patients were 79% more most likely to find that methotrexate didn’t help them enough if they were also taking at least 10 mg of prednisone per day. If they were taking at least 20 mg of predisone, then they were almost 4 times more likely to find that methotrexate wasn’t enough.

Being younger and having a high Disease Active Score (DAS28) also increased the risk that methotrexate would not be enough.

A thirty-year old with a DAS28 score of 5.5 who is taking more than 20 mg per day of prednisone along with methotrexate has a 20% probability of sticking with the methotrexate for at least the first year, the researchers estimated.

By contrast, a 50-year-old with a DAS28 of 3.5 taking less than 10 mg per day of prednisone would have an 80% probability of continuing methotrexate for the first year.