Upadacitinib, deucravacitinib ‘the top two’ small molecules for psoriatic arthritis
Key takeaways:
- For psoriatic arthritis, four small-molecule drugs were all superior to placebo and comparable with adalimumab.
- Upadacitinib and deucravacitinib consistently were in the top two across efficacy measures.
Among small-molecule drugs, upadacitinib and deucravacitinib demonstrate the best efficacy for treatment of psoriatic arthritis, according to data published in Therapeutic Advances in Musculoskeletal Disease.
“Numerous randomized controlled trials have assessed the efficacy and safety of treatments for PsA,” Ya-Chu Tsai, of the department of dermatology at Far Eastern Memorial Hospital, in Taiwan, and colleagues wrote. “However, there is a limited number of direct comparisons between different medications.
“While there have been several [network meta-analysis] articles discussing the therapeutic effects of targeted immunotherapies on PsA, most of them have primarily focused on biologic drugs, lacking a comprehensive report on small molecule treatments,” they added.
The researchers additionally noted several characteristics of small molecules that set them apart from biologics, particularly their faster onset, oral administration and broader targeting. To better understand the impacts and outcomes of various small molecules in the treatment of PsA, Tsai and colleagues conducted a network meta-analysis of studies evaluating:
- apremilast (Otelza, Amgen) 30 mg twice per day,
- deucravacitinib (Sotyktu, Bristol Myers Squibb) 6 mg or 12 mg once per day,
- tofacitinib (Xeljanz, Pfizer) 5 mg twice per day and
- upadacitinib (Rinvoq, Abbvie) 15 mg daily.
The meta-analysis ultimately included nine randomized controlled trials representing a total of 3,699 patients. To be included, patients had to report efficacy outcomes within weeks 12 to 16, as well as serious adverse events within weeks 12 to 24. Two of the studies also evaluated the biologic agent adalimumab (Humira, Abbvie).
At weeks 12 to 16, all four small-molecule drugs outperformed placebo in ACR20/50/70 measures, the Psoriasis Area and Severity Index (PASI) 75 and the Health Assessment Questionnaire Disability Index (HAQ-DI), according to the researchers.
Comparing the drugs with adalimumab, the researchers reported only one significant difference — at week 12, upadacitinib demonstrated “borderline superiority” for skin manifestations, with greater achievement of PASI 75 (RR = 1.2; 95% CI, 1.02-1.4), they wrote.
The researchers also systematically ranked the treatments against each other using league tables. According to the data, the only statistically significant difference was that deucravacitinib demonstrated better HAQ-DI scores than apremilast (RR = –0.16; 95% CI, –0.29 to –0.02).
Regarding safety, none of the small molecules showed statistically significant differences from placebo in risk for serious adverse events at week 24.
“The efficacy of all four small molecule drugs in treating PsA was superior to placebo over 12-to-16 weeks, and their effectiveness was comparable to adalimumab,” Tsai and colleagues wrote. “In addition, the risk difference for [serious adverse events] within 24weeks showed no significant difference between the small molecule drugs, placebo, and adalimumab. When considering ACR50/70, PASI 75 and HAQ-DI simultaneously, upadacitinib 15 mg [once per day] and deucravacitinib 12 mg [once per day] ranked in the top two.”
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