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Targeting IL-23 Relieves Multiple Symptoms in PsA

— Both enthesitis and dactylitis improved with guselkumab treatment in psoriatic arthritis

MedpageToday
A healthcare worker wearing white gloves holds a woman’s swollen hand

The monoclonal antibody guselkumab (Tremfya), which targets the p19 subunit of interleukin (IL)-23, was effective for treating the enthesitis and dactylitis components of psoriatic arthritis (PsA), data from a phase II study indicated.

At week 24, the change from baseline on enthesitis scores was -1.5 among patients receiving guselkumab compared with -0.7 among those given placebo (P<0.05), reported Philip J. Mease, MD, of the University of Washington in Seattle, and colleagues.

And for dactylitis, the change at week 24 was -3.8 compared with -0.4 (P<0.01) in the guselkumab and placebo groups, respectively, according to the study online in .

More than half of patients with PsA experience enthesitis and/or dactylitis, which can have significant impact on overall disease activity and functional and work impairment.

Recent work has begun to elucidate the underlying pathophysiology of enthesitis and dactylitis. For example, it appears that dactylitis may result from an to biomechanical stress or injury, initially in the innate immune system and then amplified through adaptive immune mechanisms.

IL-23 has been implicated in the pathogenesis of PsA, and particularly for the symptoms of dactylitis and arthritis. In a , exposure to this cytokine resulted in enthesitis as manifested by severe paw swelling.

Targeting this pathway is an approved strategy for psoriasis, and guselkumab also has demonstrated efficacy for PsA, Mease and co-authors noted, adding that the monoclonal antibody was for use in adults with PsA.

To explore the effects of IL-23 inhibition specifically on enthesitis and dactylitis in PsA, Mease and colleagues analyzed data from a previous , focusing specifically on patients who had those disease manifestations at baseline. The overall study included 149 patients from 34 centers in seven countries, with 107 having enthesitis and 81 having dactylitis at baseline.

The mean enthesitis score was 2.7, indicating moderate-to-severe involvement, and mean dactylitis score was 5.7 on a range of 0 to 6. The patients' average age was 45, and disease duration was about 7 years. The majority had received treatment with nonsteroidal anti-inflammatory drugs, and almost 10% had previously been treated with a tumor necrosis factor inhibitor.

Patients were randomized to receive subcutaneous guselkumab at 100 mg or placebo at weeks 0 and 4 and then every 8 weeks through week 44. At week 24, those who had initially been given placebo were switched to the active treatment.

As early as week 8, significant differences in change from baseline for enthesitis were apparent between the guselkumab and placebo groups (-1.2 vs -0.4, P<0.05). The proportion of patients with baseline enthesitis who achieved resolution at week 24 was 56.6% in the guselkumab group compared with 29% in the placebo group (P<0.05).

The percentage of patients achieving resolution of dactylitis at week 24 was 55.2% in the guselkumab group compared with 17.4% in the placebo group (P<0.01).

Among patients who crossed over from placebo to the active treatment at week 24, results were similar at week 56 to outcomes among patients on guselkumab throughout the trial. Changes from baseline on enthesitis score at week 56 were -1.9 in the guselkumab group and -2.1 in the placebo-guselkumab group, while changes on dactylitis were -5.5 in the guselkumab group and -4.4 in the placebo-guselkumab group.

At week 24, correlations were observed between changes in enthesitis scores and several other measures of disease activity:

  • Swollen joint count, r = 0.27 (P=0.02)
  • Tender joint count, r = 0.37 (P=0.001)
  • Patient's global assessment, r = 0.32 (P=0.005)
  • Short Form 36 Health Survey physical component, r = -0.27 (P=0.02)
  • Short Form 36 mental component, r = -0.35 (P=0.002)

In addition, correlations with dactylitis were seen on these measures:

  • Swollen joint count, r = 0.50 (P<0.0001)
  • Tender joint count, r = 0.38 (P=0.004)
  • Health Assessment Questionnaire Disability Index, r = 0.33 (P=0.01)

"These results suggest that guselkumab is able to improve multiple domains of disease in patients with PsA and adds to the evidence that enthesitis and dactylitis resolution are important treatment goals," the researchers stated.

A limitation of the study, they said, was its relatively small size.

Disclosures

The study was funded by Janssen.

The authors reported financial relationships with multiple companies, including Janssen, AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Novartis, Pfizer, Sun, UCB, Galapagos, Merck Sharp & Dohme, Sanofi, Roche, Leo, Allergan, Avotres, Beiersdorf, Incyte, Valeant, and XBiotech; several are employees of Janssen.

Primary Source

RMD Open: Rheumatic & Musculoskeletal Diseases

Mease P, et al "Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomized, placebo-controlled, phase II study" RMD Open 2020; DOI: 10.1136/rmdopen-2020-001217.