EXPERT ANALYSIS FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES

LAS VEGAS (FRONTLINE MEDICAL NEWS) – For patients with mild to moderate systemic lupus erythematosus, don’t go above six milligrams of prednisone daily, because the treatment is likely to be worse than the disease in the long run, said Michelle Petri, MD.

Speaking at the annual Perspectives in Rheumatic Diseases presented by Global Academy for Medical Education, Dr. Petri shared evidence-backed clinical pearls to help rheumatologists dial in good disease control for their systemic lupus erythematosus (SLE) patients without turning to too much prednisone.

“Prednisone is directly or indirectly responsible for 80% of organ damage over 15 years,” said Dr. Petri, citing data from a 2003 study ( J Rheum. 2003 Sep;30[9]:1955-9 ). “This is the analysis that I hope has buried prednisone as a long-term therapy for lupus,” said Dr. Petri , professor of medicine and director of the Lupus Center at Johns Hopkins University, Baltimore. And dosing matters, she said: “A prednisone dose of 6 mg or more increases organ damage by 50%.”

Prednisone is also an independent risk factor for cardiovascular events, with dose-dependent effects, she said. She referred to a 2012 study she coauthored ( Am J Epidemiol. 2012 Oct;176[8]:708-19 ) that found an age-adjusted cardiovascular event rate ratio of 2.4 when patients took 10-19 mg of prednisone daily (95% confidence interval [CI], 1.5-3.8; P = .0002). When the daily prednisone dose was over 20 mg, the rate ratio was 5.1 (95% CI, 3.1-8.4; P less than .0001).

Since it’s so important to minimize prednisone exposure, rheumatologists should be familiar with the full toolkit of non-immunosuppressive immunomodulators, and understand how to help patients assess risks and benefits of various treatments.“Non-immunosuppressive immunomodulators can control mild to moderate systemic lupus, helping to avoid steroids,” Dr. Petri said.

Hydroxychloroquine, when used as background therapy, has proved to have multiple benefits. Not only are flares reduced, but organ damage is reduced, lipids improve, fewer clots occur, and seizures are prevented, she said. There’s also an overall improvement in survival with hydroxychloroquine. In lupus nephritis, “continuing hydroxychloroquine improves complete response rates with mycophenolate mofetil,” Dr. Petri said.

Concerns about hydroxychloroquine-related retinopathy sometimes stand in the way of its use as background therapy, so Dr. Petri encouraged rheumatologists to have a realistic risk-benefit assessment. Higher risk for retinopathy is associated with higher dosing (greater than 6.5 mg/kg of hydroxychloroquine or 3 mg/kg of chloroquine); a higher fat body habitus, unless dosing is appropriately adjusted; the presence of renal disease or concomitant retinal disease; and age over 60.

Newer imaging techniques may sacrifice specificity for very high sensitivity in detecting hydroxychloroquine-related retinopathy, Dr. Petri said. High-speed ultra-high resolution optical coherence tomography (hsUHR-OCT) and multifocal electroretinography (mfERG) are imaging techniques that can detect hydroxychloroquine-related retinopathy, but should be reserved for patients with SLE who actually have visual symptoms, she said. Dr. Petri cited a study of 15 patients who were taking hydroxychloroquine, and 6 age-matched controls with normal visual function. All underwent visual field testing, mfERG, and hsUHR-OCT. The study “was unable to find an asymptomatic patient with evidence of definite damage on hsUHR-OCT” as well as mfERG, she said ( Arch Ophthalmol. 2007 Jun;125[6]:775-80 ).

Vitamin D supplementation gives a modest boost to overall disease control and also affords some renal protection, Dr. Petri said. She was the lead author on a 2013 study that showed that a 20-unit increase in 25-hydroxy vitamin D was associated with reduced global disease severity scores, as well as a 21% reduction in the odds of having a SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score of 5 or more, and a 15% decrease in the odds of having a urine protein to creatinine ratio greater than 0.5 ( Arthritis Rheum. 2013 Jul;65[7]:1865-71 ).

When it comes to vitamin D, more matters, Dr. Petri said. “Go above 40 [ng/mL] on vitamin D,” she said, noting that there may be pleiotropic cardiovascular and hematologic benefits as well.

Though dehydroepiandrosterone (DHEA) is not approved by the Food and Drug Administration to treat SLE, 200 mg of DHEA daily helped women with active SLE improve or stabilize disease activity, and also helped 51% of women in one study reduce prednisone to less than 7.5 mg daily, compared with 29% of women taking placebo (P = .03) ( Arthritis Rheum. 2002 Jul;46[7]:1820-9 ). There’s also “mild protection against bone loss,” Dr. Petri said.

Dr. Petri reported receiving research grants and serving as a consultant to several pharmaceutical companies. Global Academy for Medical Education and this news organization are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

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