麻豆传媒

The monoclonal antibody tildrakizumab (Ilumya), approved for plaque psoriasis, also showed efficacy for psoriatic arthritis in a phase IIb study.

At week 24, 71.4% to 79.5% of patients randomized to one of several doses of tildrakizumab had achieved a 20% improvement in joint manifestations on the criteria of the American College of Rheumatology (ACR20) compared with 50.6% of those given placebo (all P<0.01 vs placebo), according to Philip J. Mease, MD, of the University of Washington in Seattle, and colleagues.

Patients in the tildrakizumab groups also had higher rates of the more stringent ACR50 (39.7% to 52.6% vs 24.1%) and ACR70 responses (16.7% to 29.1% vs 10.1%), the investigators reported in .

A crucial factor in the pathogenesis of psoriatic arthritis is upregulation of the interleukin (IL)-23/IL-17 cytokine group. Tildrakizumab targets the IL-23 p19 subunit.

"A plausible mechanism of action of tildrakizumab is inhibition of the IL-23-induced kinase signaling system, resulting in reduced Th17 cell proliferation and downregulation of the Th17 cell-secreted inflammatory cytokines such as IL-17 and IL-22," the researchers explained.

To investigate the possibility that this medication could be beneficial in both joint and skin manifestations of psoriatic arthritis, Mease and colleagues enrolled 391 patients from 74 centers in eight countries. For the first 24 weeks, participants were randomly assigned to receive subcutaneous tildrakizumab 200 mg every 4 weeks; tildrakizumab 200 mg, 100 mg (the recommended dosage for plaque psoriasis), or 20 mg every 12 weeks; or placebo every 4 weeks. At week 24, patients in the 20 mg and placebo groups were switched to tildrakizumab 200 mg every 12 weeks, and all patients were followed through week 52.

A total of 331 patients completed the initial 24-week phase, and 315 completed the full 52 weeks.

Patients' mean age was 49, more than half were women, and almost all were white. Tumor necrosis factor inhibitors had previously been used by 23.3%. Mean disease duration was 6.0 to 7.5 years across the treatment groups, 53% to 71% had moderate-to-severe skin involvement, and more than 60% were taking conventional disease-modifying antirheumatic drugs.

The number of swollen and tender joints averaged 10 and 19, respectively, and Psoriasis Area and Severity Index (PASI) scores ranged from 5.0 to 8.8.

More patients in the tildrakizumab 200 mg every 4 weeks and 100 mg every 12 weeks groups already were considered responders at week 8, after a single dose of the drug.

At week 24, more patients in the 200 mg every 4 weeks and 200 mg every 12 weeks groups showed responses on various secondary endpoints compared with placebo (all nominal P<0.05 vs placebo):

• Disease activity score in 28 joints below 3.2: 59% and 64.6% versus 30.4%

• Minimal disease activity: 33.3% and 34.2% versus 6.3%

• Change in patient global assessment: -31.3 and -30.9 versus -20

• Change in physician global assessment: -32.7 and -36.2 versus -21.9

• Change in pain score: -31.7 and -30.4 versus -20.6

Improvements on the Health Assessment Questionnaire Disability Index were greater in the 200 mg every 12 weeks group though not the every 4 weeks group compared with placebo. No improvements in dactylitis or enthesitis were observed at week 24 in any dose groups.

Responses were maintained through week 52, and patients initially given placebo or 20 mg every 12 weeks but switched to 200 mg every 12 weeks had comparable responses at week 52 to what was observed in those treated with higher doses from baseline.

In exploratory analyses, patients whose psoriasis affected more than 3% of their body surface in all the tildrakizumab groups had achieved PASI 75%, 90%, and 100% improvements by week 24, and these responses persisted through week 52. In addition, change on the Psoriatic Arthritis Impact of Disease measurement scores declined for patients in all the tildrakizumab groups at both weeks 24 and 52.

The safety profile was similar to what was seen in the phase III trials of tildrakizumab for psoriasis. The most common adverse events were nasopharyngitis and upper respiratory tract infections. Serious adverse events were observed in 3.3% of patients, but there were no cases of systemic candidiasis, inflammatory bowel disease, uveitis, or major cardiac events.

The study demonstrated that treatment with tildrakizumab in doses of 100 mg or 200 mg was superior to placebo on multiple endpoints and was well tolerated through a year of exposure, the researchers concluded. "These results support tildrakizumab phase III clinical development in psoriatic arthritis."

A limitation of the study, the team said, was the relatively high placebo response.

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