Guselkumab drastically reduces fatigue in psoriatic arthritis patients:Study

Guselkumab (Janssen Biotech, Horsham, PA, USA), 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.It is well documented that the interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA).With this background,a team of researchers evaluated the effect of guselkumab on fatigue.

For the study protocol, across two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W, N = 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N = 375); or placebo (N = 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W. Fatigue was measured as a secondary endpoint using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue instrument (range 0–52, higher scores indicate less fatigue). Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including ≥20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc).

Results highlighted some key facts.

• Baseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N = 381) and DISCOVER-2 (N = 739), ranging from 29.1 (9.5) to 31.4 (10.1), indicated substantial levels of fatigue relative to the United States general population (43.6 [9.4]).
• Across studies, mean improvements, and proportions of patients with ≥4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W (5.6–7.6 and 54–63%, respectively) were larger vs placebo (2.2–3.6 and 35–46%).
• Improvement in FACIT-Fatigue scores with guselkumab was sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen's d = 0.52–0.81 at week 24; 0.66–0.91 at week 52).
• Mediation analyses demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 (Q4W 69–70%, Q8W 12–36% direct effect) or MDA (72–92% across dosing regimens) response or for change in serum CRP concentrations (82–88% across dosing regimens).

Observing the results, the team concluded that, "Taken together, results of these analyses indicate a strong impact of guselkumab on the fatigue of PsA when assessed via the FACIT-Fatigue instrument. 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."

For full article follow the link: https://doi.org/10.1186/s13075-021-02554-3

Source: Arthritis Research & Therapy