Rituximab Deemed Useful for Certain Lupus Subgroups

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

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

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

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

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

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