Guselkumab increases enthesitis resolution rates in psoriatic arthritis
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Treatment with guselkumab results in higher enthesitis resolutions rates at week 24, with maintenance of those higher rates through 1 year, in patients with psoriatic arthritis, according to data published in Rheumatology.
“[This study] is of immense biological relevance to psoriatic arthritis mechanisms,” Dennis McGonagle, PhD, FRCPI, of the University of Leeds, in the United Kingdom, told Healio Rheumatology. “Enthesitis is the key pathological lesion that differentiates psoriatic arthritis from rheumatoid arthritis. It is also a harbinger from future, more widespread PsA in animal models, and there is also some evidence in humans that IL-23 is an initiator of PsA. Of interest, the normal enthesis has resident IL-23 producing cells that can activate enthesis resident innate and adaptive T-cells to make IL-17 family cytokines that are also important in PsA.”
“We know that the enthesis and the IL-23 cytokine may be forerunners of disease,” he added. “Secondly, enthesitis manifests as pain, tenderness and loss of function around the body at multiple sites of tendon and ligament attachments, including around the heels, knees, pelvis, chest wall and arms. The presence of enthesitis is associated with a greater degree of disability and functional impairment than joint swelling or synovitis alone. Some anchor drugs used in PsA such as methotrexate do not work well for enthesitis. Hence, the enthesitis lesion is of immense importance to both the patient and the treating physician.”
The previously reported DISCOVER-1 and DISCOVER-2 trials demonstrated favorable benefit-risk profiles for guselkumab (Tremfya, Janssen) in patients with PsA through week 24, McGonagle and colleagues wrote. Specifically, the data revealed higher rates of enthesitis resolution among patients treated with guselkumab, compared with placebo, at week 24 when data were pooled across the trials.
To further analyze the impact of guselkumab on enthesitis and assess the links between enthesitis resolution and patient outcomes, the researchers examined pooled data from the DISCOVER-1 and DISCOVER-2 trial. Both studies were multicenter, randomized, double-blind, placebo-controlled, phase 3 trials of guselkumab in adults with active PsA despite standard therapies.
DISCOVER-1 included 381 participants with three or more tender or swollen joints and a C-reactive protein of at least 0.3 mg/dL. DISCOVER-2 enrolled 739 participants with at least five tender and swollen joints, a CRP of 0.6 mg/dL or higher and no previous biologic treatment. In both studies, participants were assigned 1:1:1 to receive either guselkumab 100mg every 4 weeks (Q4W); guselkumab 100mg at weeks 0 and 4, and then subsequently every 8 weeks (Q8W); or placebo through week 20 followed by guselkumab 100mg Q4W.
McGonagle and colleagues assessed enthesitis among the participants using Leeds Enthesitis Index (LEI) data. Findings through week 24 were predetermined in both studies to be pooled, with post hoc and week-52 analyses also included in the researchers’ assessments. In all, McGonagle and colleagues examined data from a total of 1,118 patients who had at least one evaluated LEI site.
According to the researchers, 65% of the 1,118 assessed participants demonstrated enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, as well as more systemic inflammation and impaired physical function, than those without enthesitis, they said.
Approximately 45% of pooled participants who received guselkumab Q4W, and 50% of those in the guselkumab Q8W group, achieved enthesitis resolution at week 24, compared with 29% in the placebo group (P = .0301). By week 52, 58% of participants randomized to guselkumab had achieved enthesitis resolution, including those with mild, moderate or severe cases at baseline.
In addition, among guselkumab-randomized patients with resolved enthesitis at week 24, 42% achieved minimal disease activity at week 52, compared with 17% of patients with unresolved enthesitis.
“Turning to the impact of guselkumab on enthesitis at week 24 of the study, the IL-23 inhibitor was superior to placebo in resolving pre-existing enthesitis — 45% and 50% resolution for both active drug groups versus 29% for placebo,” McGonagle said. “The high placebo rate of response is acknowledged to represent the difficulties in measuring clinical enthesitis where objective evidence of swelling is usually absent.”
“At week 52, enthesitis resolution was documented in 58% of cases, and those that were clear of enthesitis at week 24 did even better,” he added. “Overall, this shows that guselkumab demonstrated efficacy in existing enthesitis and this was associated with improvements in other aspects of disease including patient reported outcomes.”
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