SNOWMASS, COLO. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.
“In 2011, all lupus patients should receive hydroxychloroquine. The indication for hydroxychloroquine in lupus is lupus,” declared Dr. David Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.
There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life. “It will be a very long time before we've proven that any biologic therapy can do all those things,” said Dr. Wofsy, also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.
He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.
It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxy-chloroquine on the drug forthwith.
Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.
The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events.
The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).
Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator.
Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision this month.
Is belimumab a better drug for lupus than hydroxychloroquine?
Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, according to the rheumatologist.
“All of us know that Plaquenil is not the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies,” he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.
Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases.