Upadatinib and deuterated colexitinib are two large molecule drugs for the treatment of psoriatic arthritis.

According to the latest published clinical data, among small molecule drugs, Upadacitinib and Deucravacitinib have shown the best efficacy in the treatment of psoriatic arthritis (PSA). Many randomized controlled trials have evaluated the effectiveness and safety of PsA treatment. However, the number of direct comparisons between different drugs is limited. Although there are several [network meta-analysis] articles discussing the therapeutic effect of targeted immunotherapy on PsA, most of them focus mainly on biological drugs and lack comprehensive reports on small molecule treatments.

The researchers also noted several characteristics of small molecules that set them apart from biologics, particularly their faster onset of action, oral delivery and broader targeting. To better understand the impact and outcomes of various small molecules in the treatment of PsA, a network meta-analysis of studies was performed evaluating: Apremilast 30 mg twice daily; deuterated colexitinib 6 mg or 12 mg once daily; tofacitinib 5 mg twice daily; and upadatinib 15 mg daily.

The meta-analysis ultimately included9 randomized controlled trials, representing a total of 3699 patients. To be included in the study, patients must report efficacy results between weeks 12 and 16 and serious adverse events between weeks 12 and 24. Two of the studies also evaluated the biologic agent adalimumab.

The researchers said that at weeks 12 to 16, all four small molecule drugs were better than placebo on ACR20/50/70 indicators, Psoriasis Area and Severity Index (PASI) 75 and Health Assessment Questionnaire Disability Index (HAQ-DI). Comparing the drugs to adalimumab, the researchers reported only one significant difference - upadatinib showed a "marginal advantage" in skin manifestations at week 12, with a higher PASI 75 score (RR=1.2; 95% CI, 1.02-1.4).

The researchers also used league tables to systematically compare treatments with each other. According to the data, the only statistically significant difference was a better HAQ-DI score for deuterated colexitinib compared with apremilast (RR = -0.16; 95% CI, -0.29 to -0.02). Regarding safety, none of the small molecules showed a statistically significant difference from placebo in the risk of serious adverse events at week 24.

Consequently, the study results showed that all four small molecule drugs were better than placebo and comparable to adalimumab in the treatment of PsA over 12 to 16 weeks. Additionally, the difference in risk [of serious adverse events] over 24 weeks showed no significant difference between the small molecule drug, placebo, and adalimumab. When ACR50/70, PASI 75, and HAQ-DI were considered together, upadatinib 15 mg [once daily] and deuterated colexitinib 12 mg [once daily] ranked in the top two.

References:https://www.healio.com/news/rheumatology/20250210/upadacitinib-deucravacitinib-the-top-two-small-molecules-for-psoriatic-arthritis