Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by elevated levels of type 1 interferons (IFN-1). Along with relapses, patients experience persistent fatigue and reduced aerobic capacity. This study investigates how high-intensity interval training (HIIT) affects fatigue and aerobic capacity in SLE patients and whether IFN-1 influences these outcomes. Methods Fifty-three SLE patients were randomly assigned in a 1:1 ratio to either thrice-weekly HIIT sessions (21 women and 5 men) or no intervention (25 women and 2 men) for 12 weeks. The co-primary outcomes were aerobic capacity (ml O2/min/kg) and fatigue, measured by the Fatigue Severity Scale (FSS). The average treatment effects and their modification by a peripheral blood expression score of IFN-1-regulated genes were evaluated using constrained, adjusted linear mixed models. Results The HIIT intervention increased aerobic capacity by an average of 2.31 ml/kg/min compared to the control group (97.5% CI: 0.55 to 4.1; adjusted p = 0.008). However, HIIT reduced the FSS score by only 0.11 points compared to the control group (97.5% CI: −0.52 to 0.74; adjusted p > 0.99). In exploratory analyses, higher IFN-1 scores were linked to poorer HIIT outcomes, particularly regarding aerobic capacity (−0.55 ml/kg/min per SD of IFN-1 score; 95% CI: −1.37 to 0.26, adj-p = 0.295) and FSS score (0.29 per SD of IFN-1 score; CI: 0.004 to 0.58, adj-p = 0.117). However, due to multiple testing, we cannot rule out that these modifying effects may be due to chance. Conclusion Twelve weeks of HIIT significantly increased the aerobic capacity of SLE patients but did not alleviate fatigue. In exploratory analyses, high IFN-1 expression scores were negatively associated with HIIT outcomes, but further studies are needed to confirm this finding. Trial sponsor Centre for Physical Activity Research (CFAS), Rigshospitalet, Denmark. Clinical trial registration NCT05478018.
Adamsen et al. (Wed,) studied this question.