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In a large systematic review and meta-analysis, the JAK inhibitor deucravacitinib (Sotyktu) was found to markedly improve illness severity and quality of life in patients with psoriasis compared with placebo, without raising any significant safety signals.

The analysis appeared in the .

Four studies encompassing 1,663 patients were included in the meta-analysis, among whom 1,123 (67.5%) were treated with deucravacitinib with a 12-to-16-week follow-up.

A significantly higher portion of patients taking deucravacitinib achieved the Psoriasis Area and Severity Index (PASI) 75 threshold for illness severity compared with placebo (RR 5.7; 95% CI 4.32-7.53; P<0.001). Further, a minimal (i.e., 0 or 1) score on the Dermatology Life Quality Index (DLQI) (RR 3.89; 2.89-5.22; P<0.001) was also significantly more likely among patients taking deucravacitinib. The incidence of serious adverse events was similar between deucravacitinib and placebo groups.

Study co-author Philip Mease, MD, is a globally renowned rheumatologist-researcher with Swedish Medical Center, Providence St. Joseph Health, and the University of Washington School of Medicine in Washington state. His discussion with the Reading Room has been edited for length and clarity.

What was the background for embarking on this meta-analysis -- and what were the study team's key objectives?

Mease: Deucravacitinib is part of a new class of the family of JAK inhibitors that very specifically inhibits the enzyme tyrosine kinase 2 (TYK2), which blocks IL-23, IL-12, and type I interferons. The FDA for psoriasis and the medication is a promising treatment for moderate-to-severe disease. It's the first in a number of TYK2s that are coming along.

By inhibiting TYK2, you inhibit particular cytokines. And if we think about those particular cytokines, there are certain targets that they are important for. One of them is psoriasis. IL-23, for example, is a significant cytokine responsible for psoriasis manifestations. Interferon is an important pro-inflammatory molecule for lupus. IL-23 and IL-12 are both very important for psoriatic arthritis.

One of the results of the specificity of deucravacitinib is that its overall safety profile appears to be slightly better than JAK inhibitors. The drug tofacitinib (Xeljanz), which is a JAK 1 and 3 inhibitor, was tested in a large post-marketing surveillance study called Oral Surveillance for over 4,000 patients, and unfortunately there was a very slight increase in major adverse cardiovascular events in the patient population. It was also noted that there was a slight increase in malignancy compared to TNF inhibitors. So that led the .

Interestingly, deucravacitinib has escaped that issue. When the FDA approved it for psoriasis, it did not saddle the drug with that adverse safety label.

Previously, there was no study assessing deucravacitinib treatment efficacy and safety in psoriasis across all available data by meta-analysis. Hence, we performed a systematic review and meta-analysis of randomized clinical trials to evaluate disease severity reduction, quality of life improvement, and adverse event profile of deucravacitinib compared with placebo.

What are the key points for dermatologists in light of your review findings?

Mease: One of the issues that we face in treating autoimmune diseases with immune-modulatory drugs is that, over time, patients can lose response to an agent that they're using.

If it's more than a flare, sometimes we have to (as they said in the Pony Express days) trade out for a fresh horse. Sometimes we move to a different drug within the same class of drugs, but in other patients we need to move to a different mechanism of action.

That demonstrates the importance of having multiple drugs within a class and new mechanisms of action. This drug represents the first of several in this TYK2 inhibitor class to come along. That's probably, in my perspective, the most important aspect of this.

What are the implications of the review's safety findings?

Mease: Given the safety profile of this drug along with its efficacy, it's one we can give to the patient and not have to spend a great deal of time discussing potential safety issues. Being able to introduce a drug without a laundry list of safety items to discuss is a real plus. Also with this drug, you don't have to do regular laboratory monitoring because it hasn't been known to consistently cause any major laboratory abnormality, with the exception being patients with significant liver disease.

In some phase III trials with this drug, investigators compared the drug to apremilast (Otezla), another oral medication that has been popular as a treatment for psoriasis because, although it has some tolerability issues like diarrhea and so on, it is a really safe drug.

So deucravacitinib is kind of coming in as a competitor to apremilast because it has similarly good safety in addition to being more efficacious. I think it's a welcome addition.

What else does the future hold for deucravacitinib?

Mease: We're anticipating that the drug will be approved for psoriatic arthritis. Deucravacitinib also had a successful phase II trial for lupus; a phase III program is now underway. It'll be cool to have an effective oral medicine with relatively good safety for lupus as well in the future.