Study Compares Real-world Adverse Events of Methotrexate, Biologics for Psoriasis

The use of methotrexate (MTX) for routine care in patients with psoriasis was linked with a higher risk of anemia and liver adverse events (AEs) compared with biologics, according to results of a new study published in the Journal of Dermatological Treatment. However, both MTX and biologics carried similar risks of kidney injury, serious infections, and major gastrointestinal AEs in these patients.

Outside of clinical trials, limited data exist on the risk of MTX- and biologic-associated AEs for the treatment of psoriasis/psoriatic arthritis (PsA/PsO), researchers explained.

To address this knowledge gap, they carried out an observational study of 6294 adults with incident PsA/PsO in Stockholm, Sweden. All participants initiated MTX or biologics between 2006 and 2021. Researchers quantified and compared AEs including kidney, liver, hematological, serious infectious, and major gastrointestinal events for each treatment.

Although some clinical guidelines recommend MTX/adalimumab as first-line therapy for moderate to severe PsO/PsA, concerns regarding the treatments’ AEs may limit their use, authors said.

In addition, most available data on the treatments’ associated AEs come from randomized clinical trials, but many of these trials may have been too small or of too short a duration.

Moreover, “patients and clinical practice in routine care are more heterogeneous, potentially affected by lower treatment adherence, lesser monitoring at the clinic, and the presence of other comorbid conditions or ongoing medications that may potentiate AEs,” authors added.

Investigators assessed data on demographics, prescribed drugs, kidney replacement therapy outcomes, diagnoses and vital status. All participants were at least 18 years old.

The median follow-up was 4.3 years (range, 2-7 years).

Analyses revealed:

• Users of MTX had a higher risk of anemia (HR, 1.79; 95% CI, 1.48-2.16), particularly mild-moderate anemias (HR, 1.93; 95% CI, 1.49-2.50), and mild (HR, 1.46; 95% CI, 1.03-2.06) and moderate-severe liver AEs (HR, 2.22; 95% CI, 1.19-4.15) compared with biologics.
• Chronic kidney disease incidence did not differ between therapies (affecting 1.5% of the population in 5 years; HR, 1.03; 95% CI, 0.48-2.22).
• Acute kidney injury, serious infections, and major gastrointestinal AEs showed low absolute risks and no clinically meaningful differences between both therapies.

The majority of patients (86%) started with MTX and 14% started with biologics. Those who started with biologics tended to be younger and had a slightly higher average estimated glomerular filtration rate. The most frequently prescribed biologic was adalimumab.

For MTX users, “as a clinical application, this first year of therapy may be the moment where more attention should be paid to blood cell count monitoring,” authors suggested.

Despite previous research showing high doses of MTX in oncology or rheumatoid arthritis were linked with nephrotoxicity, researchers hypothesize the low dose used and general younger age and lower comorbidity profiles may have contributed to the lack of an association seen in the current study.

The observational nature of the study may have led to confounding, marking a limitation. Authors were also only able to quantify events that were detected via laboratory testing or resulted in a clinical diagnosis. Findings may also not be generalizable.

Overall, “these findings have clinical implications by demonstrating the rarity of AEs that could not be well-quantified in trials and have long been a concern (such as kidney complications attributed to low-dose MTX) that may have limited the use of these therapies,” authors wrote.

“Thus, our risk estimates may inform the choice of treatments and motivate discussions with patients about potential risks in the shared decision process of psoriasis management. Because many AEs in our study were identified by abnormal laboratory tests, our results support current guideline recommendations to monitor these tests at least once annually.,” they concluded.

Reference

Mazhar F, Krantz Å, Schalin L, Lysell J, Carrero JJ. Occurrence of adverse events associated with the initiation of methotrexate and biologics for the treatment of psoriasis in routine clinical practice. J Dermatolog Treat. Published online May 29, 2023. doi:10.1080/09546634.2023.2215354