Preemptive Corticosteroids Prevent Serious Lupus Flares in Stable Patients

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.