Study: Guselkumab demonstrated an independent treatment effe
The interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). Researchers evaluated the effect of guselkumab on fatigue.

Across two phase 3 trials of guselkuma, patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100mg every 4weeks (Q4W, N = 373); guselkumab 100mg 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).

Least-squares mean changes in FACIT-Fatigue scores were compared between treatments using a mixed-effect model for repeated measures. Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including more than 20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc).

--Baseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N = 381) and DISCOVER-2 (N = 739), ranging from 29.1 to 31.4, indicated substantial levels of fatigue relative to the United States general population (43.6).

--Across studies, mean improvements, and proportions of patients with more than 4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W were larger vs placebo.

--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 analysis demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 or MDA response or for change in serum CRP concentrations (82–88% across dosing regimens).

In conclusion, guselkumab 100 mg Q4W or Q8W led to clinically meaningful and ongoing fatigue improvements over a 1-year period in patients with active PsA. A considerable share of FACIT-Fatigue improvements caused by guselkumab were independent of the results achieved.