Early benefit with guselkumab predicts lower psoriatic arthritis progression at 2 years
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Key takeaways:
- Patients with joint improvement by week 8 had lower radiographic progression rates by week 100.
- Findings may indicate IL-23 as a pathway for future psoriatic arthritis research.
Among patients with psoriatic arthritis treated with guselkumab, early joint improvement by week 8 predicts lower radiographic progression rates through 2 years, according to data published in Clinical Rheumatology.
“Structural joint damage occurs in up to half of patients with PsA within 2 years of developing clinical symptoms, and can be characterized by bone erosion and joint space narrowing (JSN), as well as new bone formation,” Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, in Seattle, and colleagues wrote. “Guselkumab, a fully human monoclonal antibody that targets the IL-23p19 subunit, was approved to treat adults with active PsA based on findings from the phase 3 DISCOVER-1 and DISCOVER-2 trials.”
To investigate whether early clinical improvement in joint activity can predict future disease course in patients with PsA receiving guselkumab (Tremfya, Janssen), Mease and colleagues conducted a post-hoc analysis of data from DISCOVER-2, a phase 3, double-blind, placebo-controlled, multicenter study. Patients were eligible if they were aged 18 years or older, had active PsA and had a current or historical instances of psoriasis. Included patients additionally had responded poorly to, or could not receive, NSAIDs or conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and were naïve to biologics and Janus kinase inhibitors.
Patients had been randomized 1:1:1 to receive either 100 mg of guselkumab every 4 weeks; the same dose at weeks 0 and 4, and then every 8 weeks thereafter; or placebo with crossover at week 24 to guselkumab 100 mg every 4 weeks. The researchers collected radiographs of the hands and feet at baseline and weeks 24, 52 and 100. Radiographs were evaluated by independent readers, and, when necessary, a third reader provided additional judgment. Disease assessment at week 8 was based on Disease Activity Index in PsA (DAPSA).
The analysis included 739 patients. Overall, baseline age, disease duration, C-reactive protein levels and swollen joint counts correlated “weakly” with baseline PsA-modified van der Heijde-Sharp (vdH-S) scores. According to the researchers, patients who demonstrated elevated C-reactive protein levels and vdH-S scores at baseline had greater radiographic progression through 100 weeks (P < .0001). A greater improvement in DAPSA by week 8 in patients receiving guselkumab was linked to less severe radiographic progression through 100 weeks (P=.0096), they added.
“In this post hoc analysis of data from the phase 3 DISCOVER-2 study of guselkumab-treated biologic-naïve patients with active PsA, earlier (week 8) DAPSA improvement was a significant predictor of less [radiographic progression] through 2 years,” Mease and colleagues wrote. “Thus, the early and sustained control of joint disease activity with guselkumab may modify the overall long-term PsA disease trajectory to a milder course.”
Perspective
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The holy grail of disease burden reduction and prevention of radiographic progression has made dramatic improvements in the care given to patients with rheumatoid arthritis. Patients with psoriatic arthritis, however, continue to have unique challenges, as exhibited by the manifestations in the various domains of skin, enthesal inflammation, spondyloarthritis, peripheral arthritis and nail diseases.
Progression of radiographic damage in PsA is unique compared with RA, where periarticular osteopenia and erosive changes are noted. Meanwhile in PsA, enthesal new bone formation, syndesmophytes and joint erosions all may manifest in the same patients in the same or different target organs. Given these challenges, reliable studies for radiographic progression are sought to further enhance our understanding of various biologics and their anti-inflammatory properties.
The article by Mease and colleagues attempts to further elucidate this condition and seek answers on prevention of radiographic progression in PsA among patients receiving guselkumab (Tremfya, Janssen). It sheds light of the role of various disease activity measures, both clinical and laboratory, such as C-reactive protein, type 1 collagen marker (C1M) and patient reported outcomes like DAPSA. The use of a modified PsA-vdHSS score allows us to further parse out treatment improvement. As it is a post-hoc analysis, certain goals are difficult to meet since they were not pre-specified in DISCOVER2.
Secondly, a biologic-naïve, enriched patient population base, which is nowadays a dwindling population in the real world, is the premise of DISCOVER2. Having said that, this study exemplifies the role of C-reactive protein and DAPSA score in the clinical care of PsA.
Patients with active PsA treated with guselkumab who achieve earlier — ie, week 8 — meaningful improvement of DAPSA score are significantly less associated with radiographic progression. Similar findings were noted in DAPSA low disease activity arm, even when controlling for older age, male sex, increased C-reactive protein levels and higher baseline structural damage. Additionally, the role of C1M was extrapolated in this post-hoc analysis, lending itself as a unique marker that could be mined for future PsA studies, as it is indicative of structural damage.
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