TRACTISS to Study Rituximab Effects in Sjögren's Syndrome

BRIGHTON, ENGLAND – Sjögren’s syndrome may be one of the lesser known autoimmune conditions treated by rheumatologists, but research is by no means less active in trying to find novel biologic approaches to managing the often debilitating disease.

Indeed, a new study will start patient enrollment within the next few months in the United Kingdom. The multicenter TRACTISS (Trial of Anti-B-Cell Therapy in Patients With Primary Sjögren’s Syndrome) will investigate the efficacy of rituximab versus placebo in the treatment of the autoimmune connective tissue disease. The trial is planned to run for 5 years.

"Everything is falling into place to start," Dr. Simon Bowman, a principal investigator for the trial, said in an interview at the annual meeting of the British Society for Rheumatology.

Dr. Bowman, a consultant rheumatologist and honorary clinical reader at the University of Birmingham (England), added: "We’re waiting for the final ethics approval and delivery of the study drug, but the plan is to start patient recruitment in July." The aim is to recruit up to 110 patients.

According to Arthritis Research UK, which is funding the £1 million study, around half a million people in the United Kingdom have Sjögren’s syndrome.

Sjögren’s syndrome is associated with dry eyes, dry mouth, fatigue, and arthritis, Dr. Bowman explained. It can be a very disabling condition, reducing the overall quality of life of those it affects. "It can also lead to cancer of the lymph glands," he warned.

There is no cure, and current treatments for Sjögren’s target the symptoms of dry eyes and dry mouth but not always with great effect. It is hoped that, by looking at the underlying biology of the condition, which involves inflammatory cell infiltration into the salivary and lacrimal glands, more successful treatments can be developed.

"In the era of biologic therapies we should, theoretically at least, be able to devise a therapeutic approach in the glands and to ameliorate or reverse the systemic immune abnormalities," reasoned Dr. Bowman.

"The current approach is very much focused on B-cells," he added, "principally because drugs like rituximab are already available for use."

That’s not to say that a principally B-cell focused drug such as rituximab isn’t having an effect on T-cell infiltration – a predominant feature found in the salivary glands of patients with Sjögren’s syndrome.

"It’s important to bear in mind that any drug that affects the immune system will have a ripple effect, so that a drug that is normally an anti-B-cell agent will also affect the T-cells," Dr. Bowman said.

The issue is to determine if such biologic agents, regardless of whether they target B- or T-cells, could work in Sjögren’s syndrome. Already approved for use in rheumatoid arthritis and in non-Hodgkin’s lymphoma in the U.K., rituximab is backed by clinical efficacy and safety data and is, therefore, a known entity.

Although rituximab may be the "drug of the moment," Dr. Bowman noted that there were other biologic agents that could be of interest, such as belimumab, a monoclonal antibody that inhibits B-cell activation factor of the tumor necrosis factor (BAFF) or a BLyS (B-lymphocyte simulator) inhibitor.

"The [U.S. Food and Drug Administration] is currently looking at belimumab," Dr. Bowman said, adding that the National Institute for Health and Clinical Effectiveness is also considering if this agent is going to be useful for U.K. patients.

If TRACTISS is successful, then further trials will be needed for the drug’s manufacturer, Roche, to obtain a product license for Sjögren’s syndrome in the U.K. Currently, the only way for patients with Sjögren’s syndrome to receive the drug outside of a clinical trial is on a compassionate-use basis, or if they also have non-Hodgkin’s lymphoma.

TRACTISS is being funded by Arthritis Research UK. Dr. Bowman disclosed acting as consultant for Merck-Serono, Roche, and UCB.

BRIGHTON, ENGLAND – Sjögren’s syndrome may be one of the lesser known autoimmune conditions treated by rheumatologists, but research is by no means less active in trying to find novel biologic approaches to managing the often debilitating disease.

Indeed, a new study will start patient enrollment within the next few months in the United Kingdom. The multicenter TRACTISS (Trial of Anti-B-Cell Therapy in Patients With Primary Sjögren’s Syndrome) will investigate the efficacy of rituximab versus placebo in the treatment of the autoimmune connective tissue disease. The trial is planned to run for 5 years.

"Everything is falling into place to start," Dr. Simon Bowman, a principal investigator for the trial, said in an interview at the annual meeting of the British Society for Rheumatology.

Dr. Bowman, a consultant rheumatologist and honorary clinical reader at the University of Birmingham (England), added: "We’re waiting for the final ethics approval and delivery of the study drug, but the plan is to start patient recruitment in July." The aim is to recruit up to 110 patients.

According to Arthritis Research UK, which is funding the £1 million study, around half a million people in the United Kingdom have Sjögren’s syndrome.

Sjögren’s syndrome is associated with dry eyes, dry mouth, fatigue, and arthritis, Dr. Bowman explained. It can be a very disabling condition, reducing the overall quality of life of those it affects. "It can also lead to cancer of the lymph glands," he warned.

There is no cure, and current treatments for Sjögren’s target the symptoms of dry eyes and dry mouth but not always with great effect. It is hoped that, by looking at the underlying biology of the condition, which involves inflammatory cell infiltration into the salivary and lacrimal glands, more successful treatments can be developed.

"In the era of biologic therapies we should, theoretically at least, be able to devise a therapeutic approach in the glands and to ameliorate or reverse the systemic immune abnormalities," reasoned Dr. Bowman.

"The current approach is very much focused on B-cells," he added, "principally because drugs like rituximab are already available for use."

That’s not to say that a principally B-cell focused drug such as rituximab isn’t having an effect on T-cell infiltration – a predominant feature found in the salivary glands of patients with Sjögren’s syndrome.

"It’s important to bear in mind that any drug that affects the immune system will have a ripple effect, so that a drug that is normally an anti-B-cell agent will also affect the T-cells," Dr. Bowman said.

The issue is to determine if such biologic agents, regardless of whether they target B- or T-cells, could work in Sjögren’s syndrome. Already approved for use in rheumatoid arthritis and in non-Hodgkin’s lymphoma in the U.K., rituximab is backed by clinical efficacy and safety data and is, therefore, a known entity.

Although rituximab may be the "drug of the moment," Dr. Bowman noted that there were other biologic agents that could be of interest, such as belimumab, a monoclonal antibody that inhibits B-cell activation factor of the tumor necrosis factor (BAFF) or a BLyS (B-lymphocyte simulator) inhibitor.

"The [U.S. Food and Drug Administration] is currently looking at belimumab," Dr. Bowman said, adding that the National Institute for Health and Clinical Effectiveness is also considering if this agent is going to be useful for U.K. patients.

If TRACTISS is successful, then further trials will be needed for the drug’s manufacturer, Roche, to obtain a product license for Sjögren’s syndrome in the U.K. Currently, the only way for patients with Sjögren’s syndrome to receive the drug outside of a clinical trial is on a compassionate-use basis, or if they also have non-Hodgkin’s lymphoma.

TRACTISS is being funded by Arthritis Research UK. Dr. Bowman disclosed acting as consultant for Merck-Serono, Roche, and UCB.

BRIGHTON, ENGLAND – Sjögren’s syndrome may be one of the lesser known autoimmune conditions treated by rheumatologists, but research is by no means less active in trying to find novel biologic approaches to managing the often debilitating disease.

Indeed, a new study will start patient enrollment within the next few months in the United Kingdom. The multicenter TRACTISS (Trial of Anti-B-Cell Therapy in Patients With Primary Sjögren’s Syndrome) will investigate the efficacy of rituximab versus placebo in the treatment of the autoimmune connective tissue disease. The trial is planned to run for 5 years.

"Everything is falling into place to start," Dr. Simon Bowman, a principal investigator for the trial, said in an interview at the annual meeting of the British Society for Rheumatology.

Dr. Bowman, a consultant rheumatologist and honorary clinical reader at the University of Birmingham (England), added: "We’re waiting for the final ethics approval and delivery of the study drug, but the plan is to start patient recruitment in July." The aim is to recruit up to 110 patients.

According to Arthritis Research UK, which is funding the £1 million study, around half a million people in the United Kingdom have Sjögren’s syndrome.

Sjögren’s syndrome is associated with dry eyes, dry mouth, fatigue, and arthritis, Dr. Bowman explained. It can be a very disabling condition, reducing the overall quality of life of those it affects. "It can also lead to cancer of the lymph glands," he warned.

There is no cure, and current treatments for Sjögren’s target the symptoms of dry eyes and dry mouth but not always with great effect. It is hoped that, by looking at the underlying biology of the condition, which involves inflammatory cell infiltration into the salivary and lacrimal glands, more successful treatments can be developed.

"In the era of biologic therapies we should, theoretically at least, be able to devise a therapeutic approach in the glands and to ameliorate or reverse the systemic immune abnormalities," reasoned Dr. Bowman.

"The current approach is very much focused on B-cells," he added, "principally because drugs like rituximab are already available for use."

That’s not to say that a principally B-cell focused drug such as rituximab isn’t having an effect on T-cell infiltration – a predominant feature found in the salivary glands of patients with Sjögren’s syndrome.

"It’s important to bear in mind that any drug that affects the immune system will have a ripple effect, so that a drug that is normally an anti-B-cell agent will also affect the T-cells," Dr. Bowman said.

The issue is to determine if such biologic agents, regardless of whether they target B- or T-cells, could work in Sjögren’s syndrome. Already approved for use in rheumatoid arthritis and in non-Hodgkin’s lymphoma in the U.K., rituximab is backed by clinical efficacy and safety data and is, therefore, a known entity.

Although rituximab may be the "drug of the moment," Dr. Bowman noted that there were other biologic agents that could be of interest, such as belimumab, a monoclonal antibody that inhibits B-cell activation factor of the tumor necrosis factor (BAFF) or a BLyS (B-lymphocyte simulator) inhibitor.

"The [U.S. Food and Drug Administration] is currently looking at belimumab," Dr. Bowman said, adding that the National Institute for Health and Clinical Effectiveness is also considering if this agent is going to be useful for U.K. patients.

If TRACTISS is successful, then further trials will be needed for the drug’s manufacturer, Roche, to obtain a product license for Sjögren’s syndrome in the U.K. Currently, the only way for patients with Sjögren’s syndrome to receive the drug outside of a clinical trial is on a compassionate-use basis, or if they also have non-Hodgkin’s lymphoma.

TRACTISS is being funded by Arthritis Research UK. Dr. Bowman disclosed acting as consultant for Merck-Serono, Roche, and UCB.