Guselkumab 100 mg improves fatigue in psoriatic arthritis through 1 year
Guselkumab 100 mg administered every 4 or 8 weeks produced “meaningful and sustained” improvements in fatigue through 1 year in patients with psoriatic arthritis, according to data published in Arthritis & Research & Therapy.
“The mechanism underlying fatigue is complex and undefined, and it can involve physiological, psychological and social aspects,” Proton Rahman, MD, FRCPC, of the Memorial University of Newfoundland, in St. Johns, Canada, and colleagues wrote. “... To develop new therapies for effective treatment of fatigue in patients with PsA, information is needed on the causality of their fatigue, as well as efficacy associated with distinct mechanisms of action.”
“Guselkumab, a high-affinity, human monoclonal antibody specific to the interleukin (IL)-23p19-subunit, is approved to treat patients with moderate-to-severe psoriasis and active PsA,” they added. “In DISCOVER-1 and DISCOVER-2, the pivotal phase 3 studies evaluating guselkumab in patients with PsA, guselkumab effectively treated the diverse manifestations of PsA, including joint signs and symptoms, physical function, skin disease, enthesitis, dactylitis, and HRQoL, with maintenance of improvements through 1year.”
To examine the impact of guselkumab (Tremfya, Janssen) on fatigue in patients with PsA, Rahman and colleagues analyzed data — specifically the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) outcome — through 1 year from both the DISCOVER-1 and DISCOVER-2 trials. Both randomized, placebo-controlled trials comprised patients with active PsA who did not respond to, or were intolerant of, non-biologic DMARDs, apremilast and/or non-steroidal anti-inflammatory drugs.
Across the two trials, 373 participants received guselkumab 100mg at week 0 then every 4weeks; 375 were treated with guselkumab 100mg at weeks 0 and 4, then every 8weeks, with placebo at alternating 4-week intervals; and 372 received a placebo every 4 weeks. Participants in the placebo group switched to guselkumab 100mg every 4 weeks at week 24.
In the original trials, researchers assessed fatigue as a secondary endpoint with the FACIT-Fatigue tool, which uses a scale of 0 to 52 with higher scores representing less fatigue. In this study, Rahman and colleagues compared least-squares mean changes in FACIT-Fatigue scores between the treatment groups, using a mixed-effect model for repeated measures. They also used a mediation analysis to adjust for indirect impacts on fatigue that may have stemmed from improvements in other outcomes, including the American College of Rheumatology criteria (ACR20), minimal disease activity and C-reactive protein.
According to the researchers, mean baseline FACIT-Fatigue scores in DISCOVER-1 and -2 ranged from 29.1 to 31.4, suggesting high levels of fatigue.
Across both studies, mean improvements in FACIT-Fatigue scores at week 24 in participants who received guselkumab every 4 or 8 weeks ranged from 5.6 to 7.6, compared with 2.2-3.6 in the placebo group. In addition, the proportions of participants with at least 4-point improvements ranged from 54% to 63% among those who received guselkumab every 4 or 8 weeks, compared with 35% to 46% in the placebo group.
Improvements in FACIT-Fatigue scores in the guselkumab groups were sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen’s d = 0.52-0.81 at week 24, and 0.66-0.91 at week 52). Mediation analyses indicated that substantial proportions of guselkumab’s impacts on fatigue were direct effect, compared with placebo, after adjusting for ACR20 or minimal disease activity, or for changes in C-reactive protein concentrations.
“Taken together, results of these analyses indicate a strong impact of guselkumab on the fatigue of PsA when assessed via the FACIT-Fatigue instrument,” Rahman and colleagues wrote. “Although further research is needed to more fully characterize the mechanism by which guselkumab improves patient fatigue, our findings may further inform treatment decisions, additional research on this topic, and future consensus deliberations surrounding PsA core set assessments.”