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Methotrexate: Side Effects Worse for Patients With Psoriatic Arthritis

<ѻý class="mpt-content-deck">– PsA linked with more side effects than RA overall; smaller differences with TNFi

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People with psoriatic arthritis (PsA) reported more treatment side effects than people with rheumatoid arthritis (RA). This difference was more pronounced in those receiving methotrexate (MTX) than in those receiving a tumor necrosis factor inhibitor (TNFi).

The findings were published in .

The retrospective analysis used data from the FORWARD databank -- the well-known research repository for the study of arthritis and rheumatic conditions. The analysis examined 116 patients with PsA and 4,247 patients with RA who were newly initiated to MTX, and 124 patients with PsA and 4,361 patients with RA who were newly initiated to a TNFi.

People with PsA were more likely to report MTX-related side effects compared to those with RA (44.8% vs. 29.4%). A smaller percentage of patients with PsA (24.2%) reported TNFi-related side effects within the first year, just slightly more than people with RA (22.8%). Patients with PsA who initiated MTX were more likely to report nausea, vomiting, abdominal pain, depression, and tinnitus.

The following study excerpts have been edited for length and clarity.

What was the impetus for this study? What knowledge gap did it attempt to address?

Early diagnosis and effective treatment are key to patient quality of life and to slowing disease progression. PsA is treated with oral small molecules such as MTX, as well as biologic therapies, including TNFis.

Recent from the American College of Rheumatology and National Psoriasis Foundation suggest that patients with PsA could use TNFi as a first-line therapy. This change was driven in part by concerns around MTX tolerability and side effects, which can be serious enough that they cause patients to discontinue the drug.

The authors of this study aimed to fill the gap in the knowledge of treatment burden between MTX and TNFi, and between PsA and RA.

What were the study's key findings?

In this analysis, patients with PsA generally reported more side effects than those with RA -- and this was particularly evident in those initiating MTX.

Among initiators of MTX, a lower proportion of patients with RA reported a side effect in the first year of use than those with PsA. Among initiators of TNFi, the proportion of patients reporting a side effect in the first year remained similar between the RA and PsA cohorts. The analysis also showed an association between having PsA and reporting MTX-related side effects, whereas no such association was identified for TNFi users.

What were the most common side effects and how did they compare between the two diseases?

People with PsA more commonly reported nausea, numbness or tingling, GI symptoms like constipation and abdominal discomfort, and depression than those with RA.

What is the take-home message for clinicians who care for people with PsA?

Patients with PsA were also more likely to have a higher BMI, concomitant fibromyalgia, and depression, all of which may contribute to symptom profiles and side effects.

Adjusting for BMI decreased side effects of PsA compared with RA, which suggests that BMI is a meaningful confounder in this relationship and may have implications for side effects to therapy, particularly MTX.

Clinical implications

  • Methotrexate led to more side effects in people with PsA than in those with RA.
  • TNFi use was associated with similar but smaller differences in side effects.
  • People with PsA more commonly reported nausea; numbness or tingling; GI symptoms, like constipation and abdominal discomfort; and depression.

Read the study here and expert commentary on the clinical highlights here.

This study was funded by Amgen, which manufactures etanercept, a TNFIi for use in RA and PsA.

Primary Source

ACR Open Rheumatology

Source Reference:

American College of Rheumatology Publications Corner

American College of Rheumatology Publications Corner