Anti-Malaria Drug May Prevent SLE Renal Damage

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Hydroxychloroquine slowed development of renal damage in patients with systemic lupus erythematosus.

SAN FRANCISCO—Hydroxychloroquine, a low-risk and inexpensive generic drug originally used to treat malaria, may help prevent kidney damage in patients with systemic lupus erythematosus (SLE), according to new study findings presented here at the American College of Rheumatology (ACR) annual scientific meeting. 

The drug was originally used to treat SLE-associated skin and joint problems. Previous studies have shown that hydroxychloroquine is also associated with decreased flares, reduction of overall damage, and better overall survival rates in SLE patients. Because the side effects with this agent are far less common and less serious than those from other drugs used to treat lupus, such as corticosteroids and immunosuppressants, researchers at the University of Alabama in Birmingham decided to investigate whether hydroxychloroquine could prevent renal damage in lupus patients.

The study enrolled 582 African American, Caucasian, and Hispanic American SLE patients aged 16 years or older who had suffered from the disease for less than five years, but the researchers focused only on the 203 subjects who had lupus nephritis at baseline. The investigators looked at how soon renal damage occurred in those who took hydroxychloroquine (161 patients) compared with those who did not (42 patients). After adjusting for all of the variables that differed between the two groups, renal damage took much longer to occur in the hydroxychloroquine users than in the non-users. 

“The data presented, taken in conjunction with those previously reported by others, suggest that if renal damage is to be prevented, hydroxychloroquine should be prescribed to all lupus patients very early in the course of the disease,” said lead investigator Guillermo Pons-Estel, MD, a rheumatology fellow at the University of Alabama at Birmingham.

“This practice will have a direct impact not only on the lives of patients with SLE but also on society given the costs associated with … renal damage in these patients.”

Hydroxychloroquine, which costs only about $50 a month, has been associated with very few side effects, the researchers said, so they believe it may be important in preventing renal damage in this patient population. Properly monitored, this medication is quite safe, they noted.

“This medication should be used in a more generous way in all patients with lupus to try to prevent this negative effect,” study co-investigator Graciela S. Alarcón, MD, MPH, told Renal & Urology News. “Hydroxychloroquine has been used since the 1950s. It has been shown to be very safe, with only a small risk for optical side effects [optical lesions]. In 35 years as a rheumatologist, I have never seen anyone go blind from using [hydroxychloroquine].”

Dr. Alarcón, who is a professor of medicine at the University of Alabama at Birmingham, said all patients on this medication should have a vision exam once a year as a precaution.

Diabetes protection

In a separate study presented at the ACR meeting, researchers at the Geisinger Health System in Danville, Pa., found that hydroxychloroquine may prevent development of diabetes in patients with rheumatoid arthritis (RA). Last year, a study published in the Journal of the American Medical Association (2007;298:187-193) showed a 77% decrease in the incidence of diabetes in RA patients taking hydroxychloroquine for more than four years.

The Geisinger investigators studied 1,824 RA patients who had two or more office visits with a rheumatologist between September 2000 and February 2008. The patients had a mean age of 62.4 years; 74% were female and 97% were Caucasian.

Study participants were divided into two groups: 489 had previously taken hydroxychloroquine and 1,335 had not. The rate of newly diagnosed diabetes cases among hydroxychloroquine users was about half the rate observed in nonusers (17.2 vs. 33.8 new cases per 1,000 people per year). After adjusting for demographics; BMI; disease severity; and use of steroids, methotrexate, and tumor necrosis factor inhibitors, subjects who had ever used hydroxychloroquine had a 53% reduction in the risk of developing diabetes.

The researchers said they do not know what mechanism of action underlies this protective effect, but they believe that it could be related to hydroxychloroquine's immune-modulating effects and its possible favorable effects on glucose metabolism.

“Given the favorable safety profile and low cost of this generic medication, these findings may have implications for use of hydroxychloroquine to prevent diabetes in other high-risk groups,” said lead investigator Androniki Bili, MD, MPH, an attending rheumatologist at Geisinger. 

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