medwireNews: Engaging in moderate or high physical activity (PA) may significantly reduce the risk for developing systemic lupus erythematosus (SLE), independent of sociodemographic, lifestyle, and environmental factors, according to a large study.
"This study may offer particular benefits to those susceptible to SLE or individuals in the period of preclinical autoimmunity," write the researchers in Rheumatology.
Irene Wu, from the Central South University in Hunan, China, and colleagues analyzed data from 401,745 adults (mean age 56.3 years; 52.3% women) enrolled in the UK Biobank between 2006 and 2010 who were free from SLE at baseline.
The participants reported their PA levels on the International Physical Activity Short Form Questionnaire and were categorized based on the total minutes per week that they engaged in walking (3.3 METs) or moderate (4.0 METS) or vigorous (8.0 METS) PA. In all, 18.9% of patients exercised at a low level, 40.8% at a moderate level, and 40.3% at a high level.
To identify new cases of SLE, the team used a combination of self-reports, hospital records, death registry data, and ICD-10 coding. The participants were followed up until the first SLE diagnosis, death, loss to follow-up, or August 2021.
During the median 12.5 years of follow-up, 0.55% of participants developed incident SLE, while 0.27% were lost to follow-up, and 6.30% died of other causes.
Moderate and high PA levels were both linked to significantly lower SLE risk than low PA levels. Specifically, individuals with moderate and high PA had incidence rates of 3.9 and 4.3 per 100,000 person–years, respectively, compared with 6.4 per 100,000 person–years in those with low activity levels.
After adjusting for multiple confounding factors, including age, sex, education, smoking status, alcohol use, BMI, and ultraviolet exposure, patients exercising at a moderate level had a significant 40% reduced risk for incident SLE, compared with those reporting low PA at baseline, while those exercising at a high level had a significant 31% reduced risk.
Stratified analyses showed an age effect, namely that high PA more effectively prevented early-onset SLE in people younger than 50 years of age (hazard ratio [HR]=0.45), while moderate PA more strongly protected against later-onset disease in patients aged 50 years or older (HR=0.45). Sensitivity analyses – including the exclusion of SLE events occurring within 2 years of baseline and limiting follow-up to 5 years – appeared to confirm these findings.
The authors also observed sex differences, “with the protective impact of PA estimated to be approximately 2-fold greater in men than in women,” they note, adding that this disparity may be partially explained by differences in sex hormones and specific conditions such as pregnancy, menopause, and hormonal contraceptive use.
While a key strength of the study lies in its large sample size, Wu et al highlight its limitations. Most notably, the cohort consisted predominantly of White individuals aged 40–69 years, restricting the “generalizability of the findings.” Furthermore, the self-reporting of PA levels and the potential for “variations in participants’ PA levels during follow-up may also affect the results.”
The authors highlight the need for further studies to investigate whether increased PA can benefit people at high risk for SLE specifically, such as “women of childbearing age and other susceptible populations for SLE or those in the period of ‘preclinical autoimmunity’,” and whether studying the association at different stages of the disease could “provide valuable insights for developing new strategies for early treatment and prevention.”
They conclude: “To maximize potential public health gains, population-wide PA is encouraged, complemented by specific interventions targeted at those most at risk of SLE.”
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Rheumatology 2025; doi:10.1093/rheumatology/keaf150
