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TYK2 inhibition shows potential as a treatment for SLE

Presented by
Dr Marilyn Pike, MedPharm Consulting, MA, USA
ACR 2022
Phase 2, PAISLEY
In patients with systemic lupus erythematosus (SLE), deucravacitinib reached its primary endpoint of SLE Responder Index (SRI(4)) with a response rate of 58.2% on a regimen of 3 mg twice daily (BID). The study drug was deemed overall well tolerated.

The 48-week phase 2 PAISLEY trial (NCT03252587) assessed deucravacitinib as a treatment for patients with moderately to severely active SLE [1]. The study included 363 patients fulfilling inclusion criteria, namely, an SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 and ≥1 British Isles Lupus Assessment Group (BILAG) index A or >2 BILAG B manifestations from the musculoskeletal or mucocutaneous domains.

In 4 different study arms, the participants were treated with either placebo or deucravacitinib 3 mg BID, 6 mg BID, or 12 mg once daily (QD). “The patients had to be on stable background therapy, except for glucocorticoids, which were required to be tapered between weeks 8 and 20, and optionally between weeks 32 and 40, and in between those, the steroids needed to be kept stable,” Dr Marilyn Pike (MedPharm Consulting, MA, USA) further explained.

At baseline, the mean age of the study cohort was 40.1 years, and 92% were women. The mean SLEDAI-2K was 10.8, the mean count of active joints was 9, and 54.3% had at least 1 BILAG index A.

The results for the primary endpoint of SRI(4) at week 32 were statistically significant for deucravacitinib 3 mg BID and 6 mg BID versus placebo: 58.2% (P=0.0006) and 49.5% (P=0.021) versus 34.4%. “Importantly, the time to response onset was decreased to less than 3 months in the 3 mg BID and not too much greater than that in the 6 mg BID arm compared with placebo,” Dr Pike stated. Also, the secondary endpoints of SRI(4) and BILAG-based Composite Lupus Assessment (BICLA) at week 48 demonstrated superiority for deucravacitinib 3 mg BID (57.1% and 47.3%) over placebo (34.4% and 25.6%; P=0.0011 and P=0.0012, respectively). Further positive results for secondary endpoints were achieved, such as in Lupus Low Disease Activity State (LLDAS) and change in the active joint count. Overall, Dr Pike noted that no added benefit in efficacy was observed by increasing the dose of the study drug.

As for safety, adverse events occurred in 87.8% of those in the placebo arm and between 84.3% and 93.4% in the treatment groups. Serious adverse events were reported in 12.2% in the placebo arm, 7.7% in the deucravacitinib 3 mg BID arm, 7.9% in the 12 mg QD arm, and 8.6% in the 6 mg BID arm. The most common events that occurred in ≥5% of participants were upper respiratory infections, nasopharyngitis, and urinary tract infections.

“We feel that deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” Dr Pike concluded.

    1. Pike MC. Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled study. 1117, ACR Convergence 2022, 10–14 November, Philadelphia, USA.


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