B-Cell Depletion May Benefit Sjögren's Patients

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.

SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.

In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.

Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.

Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.

To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m

All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.

Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).

Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.

Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.

Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.

Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.

But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.

“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.

For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.

On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.

This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.

Only three cases of serum sickness after rituximab treatment have been reported previously, he said.