麻豆传媒

The oral JAK inhibitor upadacitinib (Rinvoq), approved for use in rheumatoid arthritis, also showed promise for psoriatic arthritis in a phase III trial comparing the drug with placebo and adalimumab (Humira).

At week 12, 20% improvements on the criteria of the American College of Rheumatology (ACR20) were seen in 70.6% of patients receiving 15 mg daily of upadacitinib; 78.5% of those given 30 mg per day; 65% of those receiving subcutaneous adalimumab, 40 mg every other week; and 36.2% of those assigned to placebo, reported Iain B. McInnes, MD, PhD, of the University of Glasgow in Scotland, and colleagues.

Both upadacitinib doses were noninferior to adalimumab on the ACR20 criteria, and the 30 mg dose was superior, the investigators reported in the study online in the .

"Upadacitinib seems like a good treatment option for the treatment of psoriatic arthritis," commented Yusuf Yazici, MD, of NYU Grossman School of Medicine in New York City, who was not involved in the study. "In my opinion, there is no clinically relevant difference between upadacitinib and adalimumab -- both seem to work well," he told 麻豆传媒.

The study, known as SELECT-PsA 1 and sponsored by AbbVie, was conducted at 281 sites in 45 countries from 2017 to 2019, with an ongoing extension phase expected to follow patients to 3 years. The current report includes data through week 24, with the primary endpoint ACR20 responses at week 12.

Participants had previously had an inadequate response or were unable to tolerate treatment with nonbiologic disease-modifying anti-rheumatic drugs.

Mean age was 50, and slightly more than half of the participants were women. Almost 90% were white, and disease duration was about 6 years.

Tender and swollen joint counts were 20 and 11, respectively, and more than 3% of body surface area was affected with psoriasis in half of the patients.

Efficacy

Regarding efficacy, at week 12, the between-group differences were:

• 15 mg upadacitinib versus placebo, 34.5 percentage points (95% CI 28.2-40.7, P<0.001)

• 30 mg upadacitinib versus placebo, 42.3 percentage points (95% CI 36.3-48.3, P<0.001)

• 30 mg upadacitinib versus adalimumab, 13.5 percentage points (95% CI 7.5-19.4, P<0.001)

• 15 mg upadacitinib versus adalimumab, 5.6 percentage points (95% CI -0.6 to 11.8)

Because of the study design, the hierarchical analysis failed with the 15 mg upadacitinib versus adalimumab comparison, so no P value was given and significance could be tested for in only some of the study's various secondary endpoints, the researchers explained.

Among the secondary endpoints that showed significant differences versus placebo for upadacitinib were change in Health Assessment Questionnaire at week 12, with a least squares mean difference from placebo of -0.28 (95% CI -0.35 to -0.22, P<0.001) for the 15 mg dose and -0.34 (95% CI -0.40 to -0.27, P<0.001) for the 30 mg dose.

Another endpoint was a 75% improvement on the Psoriasis Area and Severity Index, which had a difference versus placebo at week 16 for the 15 mg dose of 41.3 percentage points (95% CI 32.8 to 49.8, P<0.001) and 41.1 percentage points (95% CI 32.5 to 49.6, P<0.001) for the 30 mg dose.

In addition, the least squares mean difference versus placebo for radiographic changes on the modified total Sharp-van der Heijde score at week 24 for the 15 mg dose was -0.29 (95% CI -0.44 to -0.14, P<0.001) and -0.21 (95% CI -0.36 to -0.06, P=0.007) for the 30 mg dose.

Other endpoints that were significantly superior to placebo included minimal disease activity at week 24 and resolution of enthesitis at week 24. Endpoints that could not be analyzed because of the ACR20 hierarchy analysis failure included resolution of dactylitis comparing upadacitinib with placebo and change in patient's assessment of pain comparing upadacitinib with adalimumab, and change from baseline in Self Assessment of Psoriasis Symptoms comparing upadacitinib with placebo, the investigators noted.

Safety

Adverse events were assessed through week 24. Serious infections were reported in 1.2% of the upadacitinib 15 mg group, 2.6% of the 30 mg group, 0.7% of the adalimumab group, and 0.9% of the placebo group.

Hepatic disorders were reported in 9.1% and 12.3% of the 15 mg and 30 mg groups, respectively; 15.6% of the adalimumab group; and 3.8% of the placebo group.

A pulmonary embolism occurred in a patient in the 30 mg upadacitinib group, and deep-vein thromboses were reported in one patient on placebo and two in patients on adalimumab. Herpes zoster developed in four patients in the 15 mg upadacitinib group, five given the 30 mg dose, three receiving placebo, and none on adalimumab.

"Overall, there were numerically more adverse events in the two upadacitinib groups compared to adalimumab and placebo, with more events in the higher dose of upadacitinib 30 mg compared to 15 mg," Yazici noted. "The safety profile of upadacitinib, especially of the higher 30 mg dose, seems a little different than adalimumab, and this needs to be taken into consideration when thinking about which one to choose if both were available as a treatment choice for psoriatic arthritis."

"In this trial, upadacitinib at a dose of 15 mg or 30 mg once daily was more effective than placebo in most measures of psoriatic arthritis activity and inhibited radiographic progression of disease," McInnes and colleagues observed.

However, they cautioned, "longer and larger trials are required to determine the effect and risks of upadacitinib and its effects as compared with other drugs used to treat psoriatic arthritis."

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