Anti-malarials most effective in lupus patients genetically at risk of high levels of TNF-alpha

Anti-malarial drugs are most effective in people with lupus who are genetically predisposed to high levels of tumour necrosis factor alpha and low levels of the cytokine IL-10. A study published today in the journal Arthritis Research & Therapy reveals that anti-malarial drugs, widely used to treat systemic lupus erythematosus (SLE), bring serum levels of tumour necrosis factor alpha (TNF-alpha) back to normal in SLE patients. The research shows that these drugs are more effective in patients who have two specific genetic variations (polymorphisms) on the TNF-alpha and IL-10 genes that predispose them to abnormally high levels of TNF-alpha and low levels of the cytokine IL-10. This finding may have important clinical applications through the identification of lupus patients who are the most likely to benefit from anti-malarial therapy.

Patricia Lopez, from the University of Oviedo in Spain and colleagues from the Hospital Universitario Central de Asturias in Oviedo matched 192 SLE patients with 343 healthy individuals to act as controls. The researchers genotyped both patients and controls for two specific polymorphisms on the TNF-alpha and IL-10 genes. Lopez et al. then measured TNF-alpha serum levels in 171 of the SLE patients and 215 of the controls. The patients were asked precise questions regarding any treatment received before the study.

Lopez et al.’s results show that, as expected, average TNF-alpha serum levels were higher in the population of SLE patients (33.57pg/ml) than in the group of controls (19.66 pg/ml). However, patients who had been taking anti-malarial drugs for at least three months before the study had serum levels of TNF-alpha (16.64 pg/ml) similar to those of controls. Patients who had not been taking the drugs before the study had much higher levels of TNF-alpha (60.78 pg/ml).

Lopez et al. found that, in patients with both polymorphisms, TNF-alpha levels were four times lower if the patient had been taking anti-malarial drugs. For patients who do not have the polymorphisms, the difference in TNF-alpha levels was much less significant between patients who were on anti-malarial therapy and patients who were not. Patients with both polymorphisms had a four times higher probability to respond well to anti-malarial therapy (and not need any other therapy) than other patients.