Addition of Prednisone to Methotrexate May Alleviate MTX Side Effects in RA

The addition of a low to moderate dose of prednisone in patients with rheumatoid arthritis (RA) receiving treatment with methotrexate (MTX) may reduce MTX-related side effects, including nausea and elevated alanine/aspartate transaminase (ALT/AST), and increase the maximum tolerable MTX dose, according to results of a post-hoc analysis published in BMC Rheumatology.

Although MTX is standard treatment for RA, toxicity is common at a certain dose, resulting in many patients to discontinue its use. The addition of prednisone to MTX treatment may reduce certain MTX side effects; however, data are incomplete.

Researchers assessed whether the addition of prednisone to MTX could alleviate side effects and increase the maximum tolerable MTX dose.

Researchers used data from the CAMERA-II trial, in which patients with RA were randomly assigned 1:1 to receive MTX and 10 mg prednisone per day or MTX only plus placebo. To determine the impact on MTX side effects of the addition of prednisone, data were also collected from the U-ACT-Early trial, in which patients with RA were randomly assigned to receive MTX and tocilizumab or MTX and placebo.

The primary composite endpoint was occurrence of any MTX-related side effects.

In both trials, mean Disease Activity Scores 28 (DAS28) were lower in the study groups in which prednisone (mean, 2.4) or tocilizumab (mean, 2.0) were added to MTX monotherapy (mean in CAMERA-II trial, 3.0; mean in U-ACT-Early trial, 3.7).

In the CAMERA-II trial, adverse events (AEs) and MTX-related side effects were reported in 21.1% vs 26.7% and 5.9% vs 11.2% of the prednisone-MTX and MTX monotherapy groups, respectively.

In the U-ACT-Early trial, MTX-related side effects were reported in 7.6% of patients who received tocilizumab and MTX and in 10.6% of those who received MTX monotherapy.

Statistical models determined that the addition of prednisone specifically to MTX therapy reduced the occurrence of MTX-related side effects (odds ratio [OR], 0.54; P =.001). This effect was found regardless of MTX dose or level of disease activity.

Occurrence of nausea and elevated liver enzymes were reduced among patients who received treatment with MTX and addition of prednisone (OR, 0.46; P =.009 and OR, 0.29; P <.001, respectively).  

While not statistically significant, there was a trend towards fewer AEs among patients who received MTX and prednisone. In addition, the AEs often associated with prednisone use were not more likely among the MTX plus prednisone group.

As limitations, the researchers noted the study did not account for the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which could potentially affect rates of nausea and liver enzyme elevation. 

Study authors concluded, “This might specifically be of interest in patients where the maximum MTX dose is limited by side-effects, given that prednisone is tolerated well, and other measures to reduce side-effects (such as subcutaneous administration or addition of folic acid) have insufficient effect.”