WAIKOLOA, HAWAII — Every patient with lupus should be treated with an antimalarial drug, Dr. David Fiorentino said at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.
“Don't be scared to use an antimalarial. I really think this is first-line therapy. You should have a really good reason not to use one,” said Dr. Fiorentino, a dermatologist at Stanford (Calif.) University.
Antimalarials are effective for lupus skin disease, joint manifestations, and fatigue. They've also been shown to slow accrual of target-organ damage in systemic lupus erythematosus (SLE).
Moreover, SLE has been associated with an increased risk of malignancy, particularly non-Hodgkin's lymphoma, lung cancer, and hepatobiliary cancer. Antimalarial therapy may reduce this risk, according to Dr. Fiorentino. Antimalarials have been associated with an adjusted 85% reduction in the relative risk of cancer during a median 10-year follow-up in a series of SLE patients (Ann. Rheum. Dis. 2007;66:815-7).
Retinal toxicity is the most feared complication of antimalarials. It can be avoided by calculating the dose based on a patient's ideal rather than actual body weight. The key is to stay below 6.5 mg/kg of ideal body weight per day for hydroxychloroquine (Plaquenil) and below 4.0 mg/kg per day for chloroquine (Aralen).
“If you do that, you're very, very unlikely to run into retinal toxicity. It's a problem that's much more talked about than it is a reality,” said Dr. Fiorentino.
Quinacrine (Atabrine) can safely be added to either agent for greater efficacy. Just don't combine chloroquine and hydroxychloroquine because doing so can more readily lead to retinal toxicity, he added.
Dr. Fiorentino recommended a baseline eye examination including a visual field check prior to placing a patient on antimalarial therapy.
The eye exam should be repeated annually in higher-risk patients: those who are above age 60, are obese, have renal or hepatic disease, or have been on antimalarials for more than 5 years.
Second-line systemic agents for cutaneous lupus patients who do not respond adequately to antimalarials include methotrexate and mycophenolate mofetil (CellCept). These drugs lack FDA approval for use in SLE.
“They're very effective for all types of cutaneous lupus. They're not 100% effective, but I think they are the next go-to agents if antimalarials fail,” he explained.
Many lupus patients at Stanford are treated with thalidomide, according to Dr. Fiorentino. It is effective in close to 90% of patients. The clinical response is rapid: within 2 weeks at 100 mg/day, although the full response typically takes 2–3 months. Even though thalidomide is most notorious for its teratogenic effects, neurotoxicity is actually a far bigger problem.
“It's the major limiting factor. If you leave patients on thalidomide long enough, most will develop neurotoxicity,” he said.
Dapsone is quite effective in lupus complicated by vasculitis or bullous lesions and in lupus panniculitis, a highly neutrophilic disorder, he continued.
Intravenous immune globulin is primarily a temporizing measure rather than a long-term strategy.
The use of biologic agents that block tumor necrosis factor-α is controversial in lupus for several reasons. There are documented cases of lupus induced by anti-TNF agents.
Plus, the drugs often cause an increase in autoantibodies (including anti-double-stranded DNA) in patients with SLE, although the clinical significance of this phenomenon is unclear because it hasn't been accompanied by disease flares.
Dr. Fiorentino said that he has employed infliximab (Remicade) off label for lupus and has found it quite effective for renal and joint disease, but less so for skin disease. He has also prescribed the B-cell-depleting biologic rituximab (Rituxan) in cutaneous lupus, but hasn't “had a lot of success.”
Dr. Fiorentino disclosed that he is on the advisory boards of, and/or has been a paid investigator for, Abbott Laboratories, Amgen Inc., Centocor Inc., Genentech Inc., and MedImmune Inc.
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