Psoriatic arthritis

Guselkumab produces sustained enthesitis resolution in psoriatic arthritis

Treatment with guselkumab raised the chances for resolution of enthesitis among patients with psoriatic arthritis, according to a pooled analysis of two large international trials.

Enthesitis, defined as inflammation of tendon, ligament, or joint capsule insertion sites to bone, is reported in up to 54% of all patients with psoriatic arthritis (PsA). “As a potential antecedent to inflammatory and structural changes in the joint and a predominant source of pain, enthesitis confers greater disease burden in patients with PsA,” wrote study authors led by Prof Dennis McGonagle, of the University of Leeds, in Rheumatology.

Guselkumab is an anti-IL-23p19-subunit monoclonal antibody, and basic science has implicated the IL-23/IL-17 axis in the pathogenesis of PsA. The DISCOVER-1 and DISCOVER-2 trials tested the agent in two dosing regimens (every four weeks, or Q4W; and at weeks 0, 4, and 8, or Q8W) against placebo in a total of 1,118 adults with active PsA despite standard therapies.

Enthesitis was very prevalent at baseline, present in 65% of the cohort. Patients with enthesitis had more swollen and tender joints, systemic inflammation, and impaired physical function compared to those without it.

Guselkumab yielded higher rates of resolution of pre-existing enthesitis at week 24 than placebo, at 45% for Q4W and 50% for Q8W compared with 29% (p = .0301). The rates of resolution rose over time, with 58% of guselkumab-treated patients achieving resolution at week 52.

Among patients who did have resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, compared with only 17% of patients with unresolved enthesitis.

The authors note that the lack of an active comparator is an important limitation of the study, and it remains to be seen whether targeting the IL-23 p19 subunit is superior to inhibition of TNF and IL-17 in this setting.

“By targeting the IL-23 p19 subunit, guselkumab… offers a new mechanism of action by which to effect sustained resolution of enthesitis in patients with active PsA,” the authors concluded. “Enthesitis resolution was associated with achieving important patient outcomes.”

In the UK, guselkumab is indicated only for the treatment of moderate-to-severe plaque psoriasis. A recently closed consultation from the National Institute for Health and Care Excellence (NICE) recommended against its use in PsA, given the lack of direct comparison against biologic DMARDs and higher than normally acceptable cost-effectiveness estimates.

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