medwireNews: People initiating methotrexate for psoriatic arthritis (PsA) report significantly more side effects during the first year of treatment than those given the drug for rheumatoid arthritis (RA), US research shows.
There was no significant difference, however, in the proportion of patients with PsA and RA who reported side effects following initiation of a tumor necrosis factor (TNF) inhibitor, report Alexis Ogdie (University of Pennsylvania, Philadelphia) and colleagues in ACR Open Rheumatology.
They reviewed data from the FORWARD databank for patients who began treatment with methotrexate (n=116 with PsA and 4247 with RA) or a TNF inhibitor (n=124 with PsA and 4361 with RA) between 2000 and 2019.
The researchers found that 44.8% of people with PsA reported at least one side effect within a year of initiating methotrexate compared with 29.4% of those with RA, a significant difference.
The corresponding proportions among people initiating a TNF inhibitor were 24.2% for PsA and 22.8% for RA.
Specifically, patients with PsA initiating methotrexate were more likely than those with RA to report numbness or tingling (49.1 vs 36.5%), muscle weakness (43.1 v. 33.7%), headache (33.6 vs 28.3%), depression (32.8 vs 20.1%), nausea (28.4 vs 17.4%), tinnitus (27.6 vs 22.1%), constipation (26.7 vs 17.2%), nervousness (24.1 vs 17.5%), oral ulcers (24.1 vs. 14.2%), abdominal pain or cramps (21.6 vs 13.8%), and vomiting (10.3 vs 3.5%).
The rates of nausea, headache, diarrhea, depression, nervousness, and numbness or tingling were also generally higher among patients with PsA versus RA initiating a TNF inhibitor.
Ogdie et al note that the patients with PsA had a higher BMI, on average, than those with RA, and were also more likely to have fibromyalgia and depression, “which may all contribute to the symptom profile and side effects to medications.”
Indeed, in univariate analysis, people with PsA were a significant 1.95 times more likely to report side effects with methotrexate treatment than those with RA. This was attenuated slightly to 1.82-fold following adjustment for age and sex, and then to 1.77-fold with further adjustment for BMI, but remained statistically significant in both analyses.
“Adjusting for BMI decreased the effect of PsA compared with RA, which suggests that it is a meaningful confounder in this relationship and may have implications for side effects to therapy, and [methotrexate] in particular,” the authors remark.
They add: “Obesity has previously been associated with liver toxicity related to [methotrexate].”
Ogdie and team conclude that their “study is different from traditional studies assessing side effects because it uniquely analyzes patients’ experience with [methotrexate] and TNF [inhibitor] therapies.”
They say that the symptoms they identified “have meaning for patients in terms of managing their condition,” and may therefore “lead to poor treatment adherence, persistence, increased health care use, and worse clinical and patient outcomes.”
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