Biological Agents Reduce PsA Risk More Than Methotrexate in Psoriasis

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Patients with psoriasis on biological agents might have a lower PsA risk than those on methotrexate, but patients on topical therapy have an even lower risk, a study found.

A new study revealed biological agents are more effective than methotrexate in reducing the onset of psoriatic arthritis (PsA) in patients with psoriasis.1

“Our investigation also brought to light an intriguing observation: when juxtaposed with the topical therapy group, the biologics group displayed a significantly higher risk of developing PsA, especially when more than one biologic was used, which might indicate more severe disease,” wrote investigators, led by Abdulla Watad, from Tel-Aviv University in Israel.

Currently, biological therapies are approved for both psoriasis and PsA, but electronic medical record data suggests Interleukin-23 blockers may prevent the onset of PsA more than TNF blockers. However, research on this contradicted each other.

Research also shows greater psoriasis area and severity index scores—such as scores > 20, > 10, sometimes > 6—are associated with an increased PsA risk.2 Thus, treating psoriasis might prevent the development of PsA.

Investigators conducted a retrospective cohort study to compare the effectiveness of biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis.1 Leveraging data from the Israeli Meuhedet Health Services Organization database, the analysis included 58,671 patients diagnosed with psoriasis between January 1, 2000, and December 31, 2020, who were evaluated for incident PsA. The mean age at psoriasis diagnosis ranged from 32.2 to 43.3 years.

Israeli Meuhedet Health Services Organization provides healthcare coverage to 1.2 million patients across Israel. Their database includes records on diagnostic visits, pharmacological interventions, in-office procedures, laboratory test results, imaging studies, and summaries of outpatient clinic visits, emergency department visits, and in-patient discharge records.

The team categorized patients into groups based on treatment: group 1 (topical therapy), group 2 (phototherapy), group 3 (conventional disease-modifying antirheumatic drugs such as methotrexate), group 4 (biologic disease-modifying antirheumatic drugs which were stratified according to biologic class). In the cohort, 360 were treated with TNFi, 186 with anti-IL-12/23, 71 with anti-IL-17, 969 with methotrexate, 4357 with phototherapy, and 53,917 with topical therapy.

Investigators observed the PsA incidence rate was lower in the biologic agent group compared to the methotrexate group (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.35 – 0.62). Biologic treatment groups had variation in PsA incidence rates per 100 person-years, with anti-IL-12/13 or anti-IL-23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55). Despite the variation, the team observed no differences between several biological agents in their PsA prevention.

They also saw the phototherapy group demonstrated a greater incidence rate of PsA than the topical therapy group (HR, 1.85; 95% CI, 1.65 – 2.07).

However, investigators saw the risk of developing PsA was greater for individuals treated with biologics, compared to the topical treatment group (adjusted HR [aHR], 2.16; 95% CI, 1.44 – 3.24). The increased PsA risk was exhibited when examining the anti-IL-17 (aHR, 6.70; 95% CI, 2.03 – 22.05) and anti-IL-12/23 or anti-IL-23p19 groups individually (aHR, 95% CI, 2.94 – 14.53).

“This discovery invites further consideration and aligns well with the prevailing notion that PsA risk is intricately tied to high PASI scores,” investigators wrote. “It is plausible that individuals relying solely on topical therapy may have presented with lower PASI scores, thus contributing to the reduced risk of PsA.”

In contrast, the TNFi group did not show a statistically significant difference in PsA group when compared with the topical therapy group (aHR, 1.36; 95% CI, 0.79 – 2.33) nor with phototherapy (aHR, 1.36; 95% CI, 0.88 – 2.08).

Ultimately, the analysis revealed no significant differences in PsA risk between the TNFi, anti‑IL‑12/23 or anti‑IL‑23p19, and anti-IL-17 treatment groups. Conversely, patients in the methotrexate group showed a significantly greater risk of developing PsA when compared to both topical (aHR, 3.26; 95% CI, 2.68 – 3.96) or phototherapy groups (aHR, 2.19; 95% CI, 1.74 – 2.77).

Furthermore, a multivariate logistic regression analysis revealed patients exposed to ≥ 2 biological agents were linked to a significantly greater PsA risk (odds ratio [OR], 6.09; 95% CI, 3.49 – 10.64; P < .001), as well as previous methotrexate therapy (OR, 1.88; 95% CI, 1.07 – 3.27; P = .026).

“These findings collectively support the notion that severe psoriasis is a significant risk factor for PsA,” investigators wrote.


  1. Watad A, Zabotti A, Patt YS, et al. From Psoriasis to Psoriatic Arthritis: Decoding the Impact of Treatment Modalities on the Prevention of Psoriatic Arthritis. Rheumatol Ther. Published online June 7, 2024. doi:10.1007/s40744-024-00680-3
  2. Kimak A, Robak E, Makowska J, Woźniacka A. Psoriatic Arthritis: Development, Detection and Prevention: A Scoping Review. J Clin Med. 2023;12(11):3850. Published 2023 Jun 5. doi:10.3390/jcm12113850