7/3/13
by Nancy Walsh
Staff Writer, MedPage Today
- Action Points
SLE patients with low levels of 25-hydroxyvitamin D were given weekly supplements of 50,000 units of vitamin D2 plus 200 units of calcium/vitamin D3 twice daily.
- A 20-ng/ml increase in the 25(OH)D level was associated with a significant but modest decrease in the odds of having a high disease activity score and in the odds of having clinically important proteinuria.
Patients with systemic lupus erythematosus (SLE) who had low levels of vitamin D and received supplementation reduced their likelihood of having high disease activity, a large longitudinal study found.
Among patients whose 25-hydroxyvitamin D (25[OH]D) levels were below 40 ng/mL, an increase of 20 units was associated with a decline in the physician’s global assessment score of disease activity of 0.04 points (95% CI minus 0.08- minus 0.01, P=0.026), according to Michelle Petri, MD, of Johns Hopkins, and colleagues.
That represented a 13% decrease in the likelihood that the global assessment score would be 1 or higher (range 0 to 3), indicating active disease, the researchers reported in the July Arthritis & Rheumatism.
Interest has been growing in the role of vitamin D in various disease states, including autoimmune diseases like diabetes, rheumatoid arthritis, and SLE.
In particular, a possible link between SLE and low vitamin D levels has been suggested by several studies, possibly relating to inadequate sun exposure among patients with photosensitivity.
“Vitamin D insufficiency is associated with both autoantibody production and the interferon gene signature, part of the pathogenesis of SLE. Thus, there is great interest in the role of vitamin D in both the pathogenesis and maintenance of SLE,” Petri and colleagues wrote.
But clinical studies have revealed both benefits and drawbacks with vitamin D supplementation in diseases such as colorectal cancer, cardiovascular disease, and kidney disease.
To explore the potential of vitamin D supplementation in lupus, Petri and colleagues conducted a 2-year intervention study that included 1,006 members of the Hopkins Lupus Cohort, measuring their levels of 25(OH)D at each clinic visit.
Those whose levels were below the recommended 40 ng/mL were given weekly doses of 50,000 units of vitamin D along with daily supplements of 200 units of calcium/vitamin D3.
Outcomes other than the physician’s global assessment were disease activity as measured on the SELENA (Safety of Estrogens in Lupus Erythematosus National Assessment) version of the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), the protein-to-creatinine ratio of urine, and serologic markers.
Members of the cohort were primarily women whose mean age was 50. Three-quarters had insufficient levels of 25(OH)D at study outset.
The prevalence of low 25(OH)D reached 85% among African Americans (P<0.0001) and 79% among patients between 30 and 60 years of age (P=0.0070).
Patients whose 25(OH)D levels initially were below 40 ng/mL but rose by 20 units with supplementation had a decrease in SELENA-SLEDAI scores of 0.22 points (95% CI minus 0.41-minus 0.02, P=0.032), which was a 21% decrease in risk of having a SLEDAI score of 5 or higher.
An increase of 20 units also was associated with a decline of 2% in the protein-to-creatinine ratio (95% CI minus 0.03-minus 0.01, P<0.0001), which represented a 15% lower likelihood of having a ratio above 0.5 (95% CI 2-27), or “clinically important proteinuria,” the researchers noted.
After adjustment for the use of medications including immunosuppressants and angiotensin-converting enzyme inhibitors, the 20-ng/mL increase was associated with a 4% decline in the protein-to-creatinine ratio (95% CI 2-5) and with a further fall of 15% (95% CI 1-28) in the chance of having a ratio above 0.5.
“Improvement in proteinuria, even if modest (as found here) could have clinical implications,” the researchers observed.
These implications included lowering the risk for progressive chronic renal disease and direct costs of healthcare and lost productivity associated with renal involvement.
The improvements seen in physician’s global assessment and SELENA-SLEDAI also were modest, and didn’t increase further if 25(OH)D levels were increased above 40 ng/mL.
The increases in 25(OH)D levels also didn’t appear to influence serologic findings such as levels of C3 or C4 complement or anti-double-stranded DNA antibodies.
This was “surprising,” according to the researchers, because insufficient vitamin D has been linked with the so-called interferon gene signature, which, in turn, is “strongly associated” with serologic markers, the researchers explained.
The cohort will continue to be followed and 25(OH)D levels monitored, and “clinical trials of vitamin D supplementation can now be considered in SLE,” they concluded.
But until randomized trials clearly demonstrate a benefit for supplementation, clinicians should remain cautious, “given the controversy that still exists concerning the role of calcium and vitamin D in cardiovascular disease.”
A limitation of the study was the possibility of confounding by unmeasured variables.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and a General Clinical Research grant to the Johns Hopkins University School of Medicine.
The authors had no financial disclosures.
Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 07.03.2013
Primary Source
Arthritis & Rheumatism