麻豆传媒

The oral tyrosine kinase 2/Janus kinase 1 inhibitor brepocitinib showed efficacy for psoriatic arthritis (PsA) in a .

At week 16, a 20% improvement on the criteria of the American College of Rheumatology (ACR20) was observed in 66.7% of patients receiving 30 mg brepocitinib daily as did 74.6% of those given 60 mg per day compared with 43.3% of those on placebo (P<0.05 for both vs placebo), reported Philip Mease, MD, of the University of Washington in Seattle, in a presentation at the ACR virtual meeting.

Brepositinib is a small molecule oral agent that has shown promise for plaque psoriasis and alopecia areata and is now being investigated for use in PsA.

In this study, patients with active PsA who had previously had an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs (DMARDs) were randomly assigned to receive brepocitinib in dosages of 10 mg, 30 mg, or 60 mg per day or placebo through week 16, and then to 30 or 60 mg per day through week 52. Conventional DMARDs were permitted in stable doses, and up to 30% of patients could previously have used one tumor necrosis factor inhibitor.

The analysis included 218 patients, 93.1% of whom completed the 16-week phase.

Three-quarters of patients were using DMARDs at baseline, with methotrexate being the most common and in dosages of 15 mg/week. Patients also had very active disease, Mease noted, with tender and swollen joint counts averaging 16 and 10, respectively.

By week 16, significantly greater responses were seen versus placebo for both the 30- and 60-mg doses:

• ACR50 response: 48.3% and 44.1% vs 10.4%
• ACR70 response: 26.7% and 23.7% v 0.7%
• Minimal disease activity: 35% and 35.6% vs 3%

Minimal disease activity required that patients achieve at least five of these endpoints: tender joint count of 1 or less; swollen joint count of 1 or less; Psoriasis Area and Severity Index (PASI) of 1 or less or body surface area affected by psoriasis of 3% or less; patient pain rating of 15 or less; Health Assessment Questionnaire Disability Index (HAQ-DI) of 0.5 or less; and number of tender entheseal points of 1 or less.

For skin disease as measured on the PASI, a 75% improvement at week 16 was seen in 59% of the 30-mg group and in 69.2% of the 60-mg group compared with 24.4% of the placebo group, while a 90% improvement was observed in 33.3% and 53.9% versus 12.2%, respectively.

By week 52, when all patients were receiving either 30 or 60 mg per day, respective response rates were:

• ACR20: 67.6% and 60.9%
• ACR50: 54.6% and 44.6%
• ACR70: 41.7% and 36.4%
• Minimal disease activity: 46.3% and 42.7%
• PASI75: 64.2% and 60.8%
• PASI90: 53.7% and 46%

Enthesitis resolution was observed in about 60% of patients in both 30- and 60-mg groups at week 52, while resolution of dactylitis was seen in 85% and 69% of the 30- and 60-mg groups, respectively.

By week 52, pain had decreased in both 30- and 60-mg groups, as did fatigue and HAQ-DI.

During the 16-week randomized phase of the trial, adverse events were observed in 33 patients in the 30-mg group, in 40 patients in the 60-mg group, and in 32 patients in the placebo group. Most were mild in severity.

The overall safety profile was consistent with what has been seen with approved JAK inhibitors, including two cases of herpes zoster, but there were no major cardiovascular or venous thrombolic events or deaths. Serious infections and COVID-19 were uncommon.

Liver and muscle elevations were observed and were numerically more common in the 60-mg group, but there were no cases of drug-induced liver injury or cases of rhabdomyolysis.

As to the differences seen between the 30- and 60-mg groups -- for instance, with the ACR50 response at both weeks 16 and 52 being higher in the 30-mg group than in the 60-mg group -- Mease noted that this was a phase II trial, "and you can have variability and inconsistencies relating to the numbers. My own take on this is that both doses are similarly efficacious, and my understanding is that the 30-mg dose is likely to be carried forward, although I'm not sure of that," he said.

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