Patient Subgroup Response to Belimumab Remains Unclear

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.