Patients with lupus who were initially treated with medium or high doses of prednisone were likely to continue on higher doses, potentially putting them at risk for treatment-related complications, Spanish researchers reported.
Among patients given prednisone in medium dosages of 7.5 to 30 mg/day during their first month of treatment, the likelihood of continuing on dosages above 7.5 mg/day throughout the first year was 8-fold higher (OR 8.4, 95% CI 3.7 to 18.8) compared with patients not on prednisone, according to the study by , of Hospital Universitario Cruces in Barakaldo, and colleagues.
Action Points
- Note that this cohort study of newly diagnosed individuals with systemic lupus erythematosus found that higher initial steroid doses were associated with a higher cumulative steroid dose in the first year.
- While some of this relationship is due to the severity of disease, the relationship persisted even after adjustment for SLEDAI score at baseline.
And for those starting treatment on high dosages -- above 30 mg/day -- the odds of remaining on dosages above 7.5 mg/day were even higher (OR 21.2, 95% CI 9.8 to 52.6), the researchers reported online in .
In contrast, patients given low doses for the first month -- below 7.5 mg/day -- were unlikely to be on medium or high doses later in the year (OR 1.4, 95% CI 0.87 to 4.7).
"Glucocorticoids constitute one of the main therapies for systemic lupus erythematosus. However, despite their proven efficacy, oral glucocorticoids are important predictors of irreversible ," the researchers wrote.
To examine current patterns of prednisone use among patients with systemic lupus erythematosus (SLE), Ruiz-Irastorza and colleagues analyzed data from an "inception" cohort established by the Spanish Group of Autoimmune Diseases, which includes 223 patients.
The cutoff of 7.5 mg/day was used because previous experience has shown that dosages above that are more often associated with damage, the researchers noted.
The majority of patients were white women. The mean SLE Disease Activity Index (SLEDAI) score at the time of diagnosis was 9.8, and 158 of the patients had SLEDAI scores of 6 or higher, indicating active disease.
Disease manifestations included arthritis in 44% of patients, malar rash in 25%, nephritis in 21%, and thrombocytopenia in 14%.
Treatments during the first 12 months of follow-up included hydroxychloroquine in 81% of patients, prednisone in 65%, mycophenolate in 19%, pulse methylprednisolone in 15%, and azathioprine in 14%.
During the first month, 51% of patients were not on prednisone, 11% were on low doses, 21% were on medium doses, and 18% were on high doses.
Among those given medium doses during the first month, 54% remained on medium doses throughout the year, and among those with initial high doses, 75% continued on doses above 7.5 mg/day.
The cumulative dose of prednisone at the end of the first month correlated with the cumulative dose at the end of the year (R2=0.3), and the relationship persisted after adjustment for other medications including immunosuppressives and methylprednisolone pulses, and also for the presence of lupus nephritis and baseline SLEDAI.
The use of medium or high doses was associated with nephritis, thrombocytopenia, anti-DNA antibodies, and SLEDAI scores of 6 or higher at the time of diagnosis.
"It could be argued that higher initial doses are related with more severe disease, and thus, with higher needs for subsequent intensive therapy. However, this is only a partial explanation, since the influence of initial glucocorticoid therapy was independent of the baseline SLEDAI score and the presence of lupus nephritis," the researchers explained.
In a subanalysis of the 158 patients with active disease at baseline, the use of methylprednisolone pulses was associated with a lower risk of using medium or high doses of oral prednisone (OR 0.13, 95% CI 0.03 to 0.57).
"Methylprednisolone bolus may help achieve rapid remission while reducing the need for oral prednisone. Glucocorticoid therapy is a major predictor of irreversible damage in SLE, showing a strong relation with complications such as osteonecrosis, osteoporotic fractures, diabetes, cataracts, or cardiovascular disease," Ruiz-Irastorza et al wrote.
By the end of the first year of treatment, they pointed out, disease damage was present in 22% of patients, with 3 patients having had vertebral crush fractures. One of those was a 23-year-old patient who had been on 18 mg/day.
Recent studies have demonstrated that combination therapy using lower doses of prednisone are effective, both in patients and .
"Thus, maintenance doses of greater than 7.5 mg/day could and should be avoided," the authors stated. In fact, has called for the use of "the lowest glucocorticoid dosage needed to control disease, and if possible, glucocorticoids should be withdrawn completely."
A limitation of the study was its short duration, but the researchers said they hope to provide additional data on damage with longer follow-up of their cohort.
Disclosures
The study was supported by the Spanish Society of Internal Medicine.
The authors reported no financial disclosures.
Primary Source
Lupus Science & Medicine
Ruiz-Irastorza G, et al "First month prednisone dose predicts prednisone burden during the following 11 months: An observational study from the RELES cohort" Lupus Sci Med 2016; doi: 10.1136/lupus-2016-000153.