Methotrexate, TNFi Side Effects Differ in Psoriatic Arthritis and RA

methotrexate syringe
Researchers examined the prevalence of side effects with methotrexate and tumor necrosis factor inhibitors in psoriatic arthritis and rheumatoid arthritis.

Patients with psoriatic arthritis (PsA) experienced more methotrexate (MTX)-related side effects than patients with rheumatoid arthritis (RA), while similar proportions of patients with PsA and RA experienced side effects from tumor necrosis factor inhibitors (TNFis), according to findings published in ACR Open Rheumatology.

Researchers conducted a retrospective cohort study from January 2000 and January 2019 using data from the FORWARD databank in the United States. A total of 116 patients with PsA and 4247 patients with RA who initiated MTX therapy were enrolled in the MTX treatment group, and a total of 124 patients with PsA and 4361 patients with RA who initiated TNFi therapy were enrolled in the TNFi treatment group.

Patients completed questionnaires about medication side effects, concurrent medication usage, duration of treatment, and reasons for discontinuation.

The researchers analyzed the prevalence and types of side effects from MTX or TNFis after 12 months of treatment and how prevalence related to treatment burden.

Among patients who started MTX therapy, 44.8% (n=52) of patients with PsA experienced side effects within the first year of treatment compared with only 29.4% (n=1249) of patients with RA. Side effects from TNFi therapy occurred among 22.8% (n=28) of patients with PsA and 24.2% (n=1055) of patients with RA.

Compared with patients with RA, patients with PsA who received MTX therapy were more likely to report numbness or tingling, muscle weakness, headache, depression, nausea, tinnitus, constipation, nervousness, oral ulcers, pain or cramping of the abdomen, and vomiting.

While rates of side effects were similar among patients taking TNFis, those with PsA reported headache, diarrhea, depression, numbness or tingling, nervousness, and nausea more often than patients with RA.

Patients with RA in both the MTX and TNFi treatment groups experienced easier bruising than patients with PsA. 

Study limitations included lack of measurement of disease activity and the possibility of selection bias, patient recall bias, unmeasured confounding variables, confounding by indication, and order effect related to various treatment exposures. Additionally, insufficient subgroup data made it difficult to detect meaningful group differences.

“Patients with PsA reported more side effects than patients with RA, and this difference was more pronounced in those receiving MTX versus TNFi,” the study authors conclude. They add, “Such symptoms and side effects may lead to poor treatment adherence, persistence, increased health care use, and worse clinical and patient outcomes.”


Ogdie A, Maksabedian Hernandez EJ, Shaw Y, Stolshek B, Michaud K. Side effects of methotrexate and tumor necrosis factor inhibitors: Differences in tolerability among patients with psoriatic arthritis and rheumatoid arthritis. ACR Open Rheumatol. Published online August 15, 2022. doi:10.1002/acr2.11467