Sara Freeman

Major Finding: Mean change in DAS28 and HAQ scores from baseline to 6 months' follow-up were –1.4 and –0.1, respectively, indicating reduced disease severity and improved physical function in patients taking rituximab.

Data Source: Two analyses from the British Society for Rheumatology Biologics Register (BSRBR) in patients treated with the biologic agent rituximab: the first involving 550 patients with RA to evaluate the drug's efficacy; the second in 463 patients to determine predictors of response.

Disclosures: The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

BRIGHTON, ENGLAND – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the meeting by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis (RA).

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

“Rituximab has been shown to have good efficacy in clinical trials,” said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor. The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a “moderate” response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a “good” response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

“Rituximab is proven effective in the routine management of RA patients,” Ms. Soliman commented. “Response to rituximab was influenced by baseline disease activity and baseline physical function.”

Major Finding: Mean change in DAS28 and HAQ scores from baseline to 6 months' follow-up were –1.4 and –0.1, respectively, indicating reduced disease severity and improved physical function in patients taking rituximab.

Data Source: Two analyses from the British Society for Rheumatology Biologics Register (BSRBR) in patients treated with the biologic agent rituximab: the first involving 550 patients with RA to evaluate the drug's efficacy; the second in 463 patients to determine predictors of response.

Disclosures: The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

BRIGHTON, ENGLAND – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the meeting by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis (RA).

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

“Rituximab has been shown to have good efficacy in clinical trials,” said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor. The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a “moderate” response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a “good” response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

“Rituximab is proven effective in the routine management of RA patients,” Ms. Soliman commented. “Response to rituximab was influenced by baseline disease activity and baseline physical function.”

Major Finding: Mean change in DAS28 and HAQ scores from baseline to 6 months' follow-up were –1.4 and –0.1, respectively, indicating reduced disease severity and improved physical function in patients taking rituximab.

Data Source: Two analyses from the British Society for Rheumatology Biologics Register (BSRBR) in patients treated with the biologic agent rituximab: the first involving 550 patients with RA to evaluate the drug's efficacy; the second in 463 patients to determine predictors of response.

Disclosures: The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

BRIGHTON, ENGLAND – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the meeting by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis (RA).

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

“Rituximab has been shown to have good efficacy in clinical trials,” said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor. The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a “moderate” response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a “good” response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

“Rituximab is proven effective in the routine management of RA patients,” Ms. Soliman commented. “Response to rituximab was influenced by baseline disease activity and baseline physical function.”

LONDON – Biologic treatment may open a “therapeutic window” for the improved nonmedical management of rheumatoid arthritis, according to a leading Swedish physiotherapist.

The advent of biologics just over a decade ago has undoubtedly tightened disease control and improved outcomes, compared with more conventional therapies for many patients with RA.

But biologics have also made it much more possible for patients to undertake prescribed exercise regimens that are recommended for older adults with chronic diseases such as arthritis, said Christina Opava of the Karolinska Institutet and Karolinska University Hospital in Stockholm.

“Biologics do not necessarily take away the need for exercise, but they may open up a therapeutic window for people to regain and maintain their physical activity while on treatment,” she noted.

In an interview, Ms. Opava added that “everything is not about disease control. We also need to pay attention to a healthy lifestyle.”

Over the past few decades, the treatment of RA has changed dramatically, with improved medications and nonmedical options. In addition, many more patients today are empowered to self-manage their condition, and have greater expectations of and worries about how treatments and their disease will affect their overall quality and duration of life.

In a recent review article, four nonpharmacologic options topped the list of strategies that have a sound evidence base: self-management interventions, exercise or a suitable physical activity program, comprehensive occupational therapy with patients who are able to work but are at risk of losing their jobs, and use of wrist and finger splints (Curr. Opin. Rheumatol. 2011;23:259–64).

More research is needed on the use of assistive devices, foot orthoses, and dietary interventions in order to determine the true effectiveness of the strategies, the review authors suggested.

Having worked as a rheumatology health care professional for more than 30 years, Ms. Opava emphasized that nonmedical options should not be forgotten. Strategies to help patients self-manage their condition, for example, may include tailored patient education, behavioral and cognitive approaches, and individualized weekly action plans (Ann. Rheum. Dis. 2010;69:955–63).

Ms. Opava's research has focused on the benefits of regular exercise in arthritis, and determining what the minimum amount of exercise could be and how this could be most effectively prescribed (Arthritis Rheum. 2003;49:428-34). Planned and structured exercise has been shown to be effective in RA, and “by now, there are enough studies to support its safety as well as its benefit,” she said.

Not all patients may be able to partake in the same level or type of exercise, which – according to the American College of Sports Medicine guidelines – can be the same for adults aged 50–64 years with a chronic condition such as arthritis and those aged 65 years or older.”

“Everyone has to choose their own mode of exercise,” Ms. Opava explained, noting that health care professionals need to assess the patient's physical capacity before prescribing any form of exercise or physical activity program. Exercise and physical activity also need to be enjoyable for patients, so that there is greater likelihood that patients will stick with their exercise regimen.

Patient education and empowerment are vital to achieving and maintaining a healthy lifestyle that includes appropriate exercise and physical activity. All health care professionals who treat patients with arthritis should reinforce the benefits of healthy living as a central component of managing the condition, she said.

“Most of us know what a healthy lifestyle is, but it's more difficult to lead a healthy lifestyle consistently,” she added, noting that it basically involved physical activity, a healthful diet, moderate alcohol intake, and no smoking.

Ms. Opava had no conflicts of interest to declare.

LONDON – Biologic treatment may open a “therapeutic window” for the improved nonmedical management of rheumatoid arthritis, according to a leading Swedish physiotherapist.

The advent of biologics just over a decade ago has undoubtedly tightened disease control and improved outcomes, compared with more conventional therapies for many patients with RA.

But biologics have also made it much more possible for patients to undertake prescribed exercise regimens that are recommended for older adults with chronic diseases such as arthritis, said Christina Opava of the Karolinska Institutet and Karolinska University Hospital in Stockholm.

“Biologics do not necessarily take away the need for exercise, but they may open up a therapeutic window for people to regain and maintain their physical activity while on treatment,” she noted.

In an interview, Ms. Opava added that “everything is not about disease control. We also need to pay attention to a healthy lifestyle.”

Over the past few decades, the treatment of RA has changed dramatically, with improved medications and nonmedical options. In addition, many more patients today are empowered to self-manage their condition, and have greater expectations of and worries about how treatments and their disease will affect their overall quality and duration of life.

In a recent review article, four nonpharmacologic options topped the list of strategies that have a sound evidence base: self-management interventions, exercise or a suitable physical activity program, comprehensive occupational therapy with patients who are able to work but are at risk of losing their jobs, and use of wrist and finger splints (Curr. Opin. Rheumatol. 2011;23:259–64).

More research is needed on the use of assistive devices, foot orthoses, and dietary interventions in order to determine the true effectiveness of the strategies, the review authors suggested.

Having worked as a rheumatology health care professional for more than 30 years, Ms. Opava emphasized that nonmedical options should not be forgotten. Strategies to help patients self-manage their condition, for example, may include tailored patient education, behavioral and cognitive approaches, and individualized weekly action plans (Ann. Rheum. Dis. 2010;69:955–63).

Ms. Opava's research has focused on the benefits of regular exercise in arthritis, and determining what the minimum amount of exercise could be and how this could be most effectively prescribed (Arthritis Rheum. 2003;49:428-34). Planned and structured exercise has been shown to be effective in RA, and “by now, there are enough studies to support its safety as well as its benefit,” she said.

Not all patients may be able to partake in the same level or type of exercise, which – according to the American College of Sports Medicine guidelines – can be the same for adults aged 50–64 years with a chronic condition such as arthritis and those aged 65 years or older.”

“Everyone has to choose their own mode of exercise,” Ms. Opava explained, noting that health care professionals need to assess the patient's physical capacity before prescribing any form of exercise or physical activity program. Exercise and physical activity also need to be enjoyable for patients, so that there is greater likelihood that patients will stick with their exercise regimen.

Patient education and empowerment are vital to achieving and maintaining a healthy lifestyle that includes appropriate exercise and physical activity. All health care professionals who treat patients with arthritis should reinforce the benefits of healthy living as a central component of managing the condition, she said.

“Most of us know what a healthy lifestyle is, but it's more difficult to lead a healthy lifestyle consistently,” she added, noting that it basically involved physical activity, a healthful diet, moderate alcohol intake, and no smoking.

Ms. Opava had no conflicts of interest to declare.

LONDON – Biologic treatment may open a “therapeutic window” for the improved nonmedical management of rheumatoid arthritis, according to a leading Swedish physiotherapist.

The advent of biologics just over a decade ago has undoubtedly tightened disease control and improved outcomes, compared with more conventional therapies for many patients with RA.

But biologics have also made it much more possible for patients to undertake prescribed exercise regimens that are recommended for older adults with chronic diseases such as arthritis, said Christina Opava of the Karolinska Institutet and Karolinska University Hospital in Stockholm.

“Biologics do not necessarily take away the need for exercise, but they may open up a therapeutic window for people to regain and maintain their physical activity while on treatment,” she noted.

In an interview, Ms. Opava added that “everything is not about disease control. We also need to pay attention to a healthy lifestyle.”

Over the past few decades, the treatment of RA has changed dramatically, with improved medications and nonmedical options. In addition, many more patients today are empowered to self-manage their condition, and have greater expectations of and worries about how treatments and their disease will affect their overall quality and duration of life.

In a recent review article, four nonpharmacologic options topped the list of strategies that have a sound evidence base: self-management interventions, exercise or a suitable physical activity program, comprehensive occupational therapy with patients who are able to work but are at risk of losing their jobs, and use of wrist and finger splints (Curr. Opin. Rheumatol. 2011;23:259–64).

More research is needed on the use of assistive devices, foot orthoses, and dietary interventions in order to determine the true effectiveness of the strategies, the review authors suggested.

Having worked as a rheumatology health care professional for more than 30 years, Ms. Opava emphasized that nonmedical options should not be forgotten. Strategies to help patients self-manage their condition, for example, may include tailored patient education, behavioral and cognitive approaches, and individualized weekly action plans (Ann. Rheum. Dis. 2010;69:955–63).

Ms. Opava's research has focused on the benefits of regular exercise in arthritis, and determining what the minimum amount of exercise could be and how this could be most effectively prescribed (Arthritis Rheum. 2003;49:428-34). Planned and structured exercise has been shown to be effective in RA, and “by now, there are enough studies to support its safety as well as its benefit,” she said.

Not all patients may be able to partake in the same level or type of exercise, which – according to the American College of Sports Medicine guidelines – can be the same for adults aged 50–64 years with a chronic condition such as arthritis and those aged 65 years or older.”

“Everyone has to choose their own mode of exercise,” Ms. Opava explained, noting that health care professionals need to assess the patient's physical capacity before prescribing any form of exercise or physical activity program. Exercise and physical activity also need to be enjoyable for patients, so that there is greater likelihood that patients will stick with their exercise regimen.

Patient education and empowerment are vital to achieving and maintaining a healthy lifestyle that includes appropriate exercise and physical activity. All health care professionals who treat patients with arthritis should reinforce the benefits of healthy living as a central component of managing the condition, she said.

“Most of us know what a healthy lifestyle is, but it's more difficult to lead a healthy lifestyle consistently,” she added, noting that it basically involved physical activity, a healthful diet, moderate alcohol intake, and no smoking.

Ms. Opava had no conflicts of interest to declare.

BRIGHTON, ENGLAND – The arrival of biologic agents for the treatment of rheumatic disease has been hailed as a groundbreaking event, with their practical use undoubtedly aided by the setup and success of large-scale biologics registers in Europe.

“I think we've been very privileged in the past 10 years to have lived through an era where, rather similar to the introduction of steroids, a truly epoch-making set of drugs have come to the fore,” said Dr. David Isenberg. “They have really changed the way we practice in a way that was unimaginable 15 years ago.”

Dr. Isenberg, who recently stepped down as the chair of the BSRBR (British Society for Rheumatology Biologics Register) Steering Committee, added that “one very important aspect of the way in which these new drugs have been introduced is the growth of the biologics registers, which have been developed to monitor their use.”

Started in 2001, the BSRBR has now become the largest of the European biologics registers, with data still being collected on more than 20,000 participants with rheumatoid arthritis, of whom around 15,000 are receiving anti–tumor necrosis factor–alpha agents.

A year after the register started, the U.K. National Institute for Health and Clinical Excellence (NICE) published guidelines on the use of biologics and recommended that all patients who start treatment with the new agents should be included in the BSRBR.

“Almost immediately, the number of patients recruited per month increased – almost exponentially,” said Dr. Deborah Symmons, one of the two principal investigators for the BSRBR.

In fact, it was more difficult to recruit the comparison cohort of patients with active RA who were being treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs) and were anti-TNF naive.

Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the Arthritis Research UK Epidemiology Unit at the University of Manchester (England), noted, “It's the only study I've ever been involved with where we massively exceeded our sample size in less than the time that was estimated.”

With the recent call for clinicians to start registering patients who are being treated with certolizumab (the latest anti-TNF to gain NICE approval in the United Kingdom), the BSRBR continues to increase its patient numbers. The addition of tocilizumab and abatacept to the register is also planned in the near future.

In addition to the large patient numbers and power of the data that can be generated, the key to the success of the BSRBR is its ability to evolve and change with the times. When the register was started, the primary aim was to see if anti-TNF agents increased the risk of cancer (specifically non-Hodgkin's lymphoma) relative to nonbiologic DMARDs. Additional goals were added over the years, and – to enable long-term comparisons of all drugs in the register – an extended follow-up of all treatment arms was announced just last year.

The BSRBR is one of the few biologics registers to include a control arm of the standard therapy of the time (nonbiologic DMARDs). Because of changing baseline characteristics and anti-TNFs themselves becoming established therapy, however, recruitment into a second, anti-TNF cohort arm has just begun. Patients who start treatment with one of the older anti-TNF agents included in the register (infliximab, etanercept, or adalimumab) are eligible for inclusion into the new cohort. Newer agents entering the register will then be compared with the anti-TNF control cohort.

“Registers are epidemiologic cohort studies dedicated to pharmacovigilance and real-life effectiveness,” commented Dr. Angela Zink, one of the key people behind the 13,000-patient German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), which also includes a control arm.

Dr. Zink, deputy director of the German Rheumatism Research Centre and professor of epidemiology of rheumatic diseases at the Charité Medical University Berlin, observed that biologics registers were “long-term enterprises,” with payback only many years after their initial setup.”

“In the end, registries allow you to answer questions that you couldn't answer with other types of studies,” Dr. Zink noted. Indeed, about one-third of patients in RABBIT would not have been eligible for clinical trials and, without the register, would not have been treated with anti-TNFs, she observed.

Without the buy-in of the large pharmaceutical companies that make biologic agents, however, the registers would be impossible to run. Although the BSRBR is funded through the BSR, which in turn has six separate contracts with the relevant manufacturers of biologics in the United Kingdom, the German register has managed to develop a single, seven-way contract with all manufacturers in Germany.

“At the end of the day it works because everyone benefits,” he said. The companies essentially get 5 years of follow-up data on their products while the researchers are able to publish their findings in the top rheumatology journals. In addition, “the BSR gets the kudos of running the world's largest biologics register.”

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Isenberg and Dr. Symmons declared that they had no personal conflicts of interest. Dr. Zink has received research grants from Abbott, Amgen, Bristol-Myers Squibb, Essex Pharma, Pfizer, Roche, and UCB.

BRIGHTON, ENGLAND – The arrival of biologic agents for the treatment of rheumatic disease has been hailed as a groundbreaking event, with their practical use undoubtedly aided by the setup and success of large-scale biologics registers in Europe.

“I think we've been very privileged in the past 10 years to have lived through an era where, rather similar to the introduction of steroids, a truly epoch-making set of drugs have come to the fore,” said Dr. David Isenberg. “They have really changed the way we practice in a way that was unimaginable 15 years ago.”

Dr. Isenberg, who recently stepped down as the chair of the BSRBR (British Society for Rheumatology Biologics Register) Steering Committee, added that “one very important aspect of the way in which these new drugs have been introduced is the growth of the biologics registers, which have been developed to monitor their use.”

Started in 2001, the BSRBR has now become the largest of the European biologics registers, with data still being collected on more than 20,000 participants with rheumatoid arthritis, of whom around 15,000 are receiving anti–tumor necrosis factor–alpha agents.

A year after the register started, the U.K. National Institute for Health and Clinical Excellence (NICE) published guidelines on the use of biologics and recommended that all patients who start treatment with the new agents should be included in the BSRBR.

“Almost immediately, the number of patients recruited per month increased – almost exponentially,” said Dr. Deborah Symmons, one of the two principal investigators for the BSRBR.

In fact, it was more difficult to recruit the comparison cohort of patients with active RA who were being treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs) and were anti-TNF naive.

Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the Arthritis Research UK Epidemiology Unit at the University of Manchester (England), noted, “It's the only study I've ever been involved with where we massively exceeded our sample size in less than the time that was estimated.”

With the recent call for clinicians to start registering patients who are being treated with certolizumab (the latest anti-TNF to gain NICE approval in the United Kingdom), the BSRBR continues to increase its patient numbers. The addition of tocilizumab and abatacept to the register is also planned in the near future.

In addition to the large patient numbers and power of the data that can be generated, the key to the success of the BSRBR is its ability to evolve and change with the times. When the register was started, the primary aim was to see if anti-TNF agents increased the risk of cancer (specifically non-Hodgkin's lymphoma) relative to nonbiologic DMARDs. Additional goals were added over the years, and – to enable long-term comparisons of all drugs in the register – an extended follow-up of all treatment arms was announced just last year.

The BSRBR is one of the few biologics registers to include a control arm of the standard therapy of the time (nonbiologic DMARDs). Because of changing baseline characteristics and anti-TNFs themselves becoming established therapy, however, recruitment into a second, anti-TNF cohort arm has just begun. Patients who start treatment with one of the older anti-TNF agents included in the register (infliximab, etanercept, or adalimumab) are eligible for inclusion into the new cohort. Newer agents entering the register will then be compared with the anti-TNF control cohort.

“Registers are epidemiologic cohort studies dedicated to pharmacovigilance and real-life effectiveness,” commented Dr. Angela Zink, one of the key people behind the 13,000-patient German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), which also includes a control arm.

Dr. Zink, deputy director of the German Rheumatism Research Centre and professor of epidemiology of rheumatic diseases at the Charité Medical University Berlin, observed that biologics registers were “long-term enterprises,” with payback only many years after their initial setup.”

“In the end, registries allow you to answer questions that you couldn't answer with other types of studies,” Dr. Zink noted. Indeed, about one-third of patients in RABBIT would not have been eligible for clinical trials and, without the register, would not have been treated with anti-TNFs, she observed.

Without the buy-in of the large pharmaceutical companies that make biologic agents, however, the registers would be impossible to run. Although the BSRBR is funded through the BSR, which in turn has six separate contracts with the relevant manufacturers of biologics in the United Kingdom, the German register has managed to develop a single, seven-way contract with all manufacturers in Germany.

“At the end of the day it works because everyone benefits,” he said. The companies essentially get 5 years of follow-up data on their products while the researchers are able to publish their findings in the top rheumatology journals. In addition, “the BSR gets the kudos of running the world's largest biologics register.”

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Isenberg and Dr. Symmons declared that they had no personal conflicts of interest. Dr. Zink has received research grants from Abbott, Amgen, Bristol-Myers Squibb, Essex Pharma, Pfizer, Roche, and UCB.

BRIGHTON, ENGLAND – The arrival of biologic agents for the treatment of rheumatic disease has been hailed as a groundbreaking event, with their practical use undoubtedly aided by the setup and success of large-scale biologics registers in Europe.

“I think we've been very privileged in the past 10 years to have lived through an era where, rather similar to the introduction of steroids, a truly epoch-making set of drugs have come to the fore,” said Dr. David Isenberg. “They have really changed the way we practice in a way that was unimaginable 15 years ago.”

Dr. Isenberg, who recently stepped down as the chair of the BSRBR (British Society for Rheumatology Biologics Register) Steering Committee, added that “one very important aspect of the way in which these new drugs have been introduced is the growth of the biologics registers, which have been developed to monitor their use.”

Started in 2001, the BSRBR has now become the largest of the European biologics registers, with data still being collected on more than 20,000 participants with rheumatoid arthritis, of whom around 15,000 are receiving anti–tumor necrosis factor–alpha agents.

A year after the register started, the U.K. National Institute for Health and Clinical Excellence (NICE) published guidelines on the use of biologics and recommended that all patients who start treatment with the new agents should be included in the BSRBR.

“Almost immediately, the number of patients recruited per month increased – almost exponentially,” said Dr. Deborah Symmons, one of the two principal investigators for the BSRBR.

In fact, it was more difficult to recruit the comparison cohort of patients with active RA who were being treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs) and were anti-TNF naive.

Dr. Symmons, professor of rheumatology and musculoskeletal epidemiology at the Arthritis Research UK Epidemiology Unit at the University of Manchester (England), noted, “It's the only study I've ever been involved with where we massively exceeded our sample size in less than the time that was estimated.”

With the recent call for clinicians to start registering patients who are being treated with certolizumab (the latest anti-TNF to gain NICE approval in the United Kingdom), the BSRBR continues to increase its patient numbers. The addition of tocilizumab and abatacept to the register is also planned in the near future.

In addition to the large patient numbers and power of the data that can be generated, the key to the success of the BSRBR is its ability to evolve and change with the times. When the register was started, the primary aim was to see if anti-TNF agents increased the risk of cancer (specifically non-Hodgkin's lymphoma) relative to nonbiologic DMARDs. Additional goals were added over the years, and – to enable long-term comparisons of all drugs in the register – an extended follow-up of all treatment arms was announced just last year.

The BSRBR is one of the few biologics registers to include a control arm of the standard therapy of the time (nonbiologic DMARDs). Because of changing baseline characteristics and anti-TNFs themselves becoming established therapy, however, recruitment into a second, anti-TNF cohort arm has just begun. Patients who start treatment with one of the older anti-TNF agents included in the register (infliximab, etanercept, or adalimumab) are eligible for inclusion into the new cohort. Newer agents entering the register will then be compared with the anti-TNF control cohort.

“Registers are epidemiologic cohort studies dedicated to pharmacovigilance and real-life effectiveness,” commented Dr. Angela Zink, one of the key people behind the 13,000-patient German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy), which also includes a control arm.

Dr. Zink, deputy director of the German Rheumatism Research Centre and professor of epidemiology of rheumatic diseases at the Charité Medical University Berlin, observed that biologics registers were “long-term enterprises,” with payback only many years after their initial setup.”

“In the end, registries allow you to answer questions that you couldn't answer with other types of studies,” Dr. Zink noted. Indeed, about one-third of patients in RABBIT would not have been eligible for clinical trials and, without the register, would not have been treated with anti-TNFs, she observed.

Without the buy-in of the large pharmaceutical companies that make biologic agents, however, the registers would be impossible to run. Although the BSRBR is funded through the BSR, which in turn has six separate contracts with the relevant manufacturers of biologics in the United Kingdom, the German register has managed to develop a single, seven-way contract with all manufacturers in Germany.

“At the end of the day it works because everyone benefits,” he said. The companies essentially get 5 years of follow-up data on their products while the researchers are able to publish their findings in the top rheumatology journals. In addition, “the BSR gets the kudos of running the world's largest biologics register.”

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Isenberg and Dr. Symmons declared that they had no personal conflicts of interest. Dr. Zink has received research grants from Abbott, Amgen, Bristol-Myers Squibb, Essex Pharma, Pfizer, 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.

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 – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the annual meeting of the British Society for Rheumatology (BSR) by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis.

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

"Rituximab has been shown to have good efficacy in clinical trials," said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor.

The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a "moderate" response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a "good" response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

"Rituximab is proven effective in the routine management of RA patients," Ms. Soliman commented. "Response to rituximab was influenced by baseline disease activity and baseline physical function."

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

BRIGHTON, ENGLAND – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the annual meeting of the British Society for Rheumatology (BSR) by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis.

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

"Rituximab has been shown to have good efficacy in clinical trials," said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor.

The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a "moderate" response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a "good" response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

"Rituximab is proven effective in the routine management of RA patients," Ms. Soliman commented. "Response to rituximab was influenced by baseline disease activity and baseline physical function."

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

BRIGHTON, ENGLAND – Rituximab is an effective treatment for established rheumatoid arthritis in routine clinical practice, with response predicted by baseline disease activity and functional status, based on data from the British Society for Rheumatology Biologics Register.

Rituximab has been licensed for use in combination with methotrexate since 2006 in both the United States and the United Kingdom, and is generally used after treatment failure with traditional nonbiologic disease-modifying antirheumatic drugs (DMARDs) and at least one anti–tumor necrosis factor–alpha (anti-TNF-alpha) agent.

Two analyses, presented at the annual meeting of the British Society for Rheumatology (BSR) by Moetaza Soliman and her associates, highlighted the real-world use of the biologic agent in patients with severe, active rheumatoid arthritis.

Coauthors of the research included the two principal investigators of the BSRBR – Dr. Deborah Symmons and Dr. Kimmie Hyrich, both of the arthritis research U.K. epidemiology unit at the University of Manchester (England).

"Rituximab has been shown to have good efficacy in clinical trials," said Ms. Soliman, a doctoral researcher at the university. Whether the same can be said in everyday practice was the focus of the first evaluation of data from the BSR Biologics Register (BSRBR).

The overall efficacy of rituximab was examined in 550 patients treated with the drug up until a data cutoff of October 2010. The analysis involved all patients who were treated with the biologic agent, and looked at clinical and patient-reported outcomes 6 months after treatment was started.

The mean age of patients was 59 years, 78% were female, and the mean disease duration was 15 years. One-third of the cohort was seronegative for rheumatoid factor.

The majority (84%) of patients had been treated with anti-TNF therapy, with 53% failing one, 37% two, and 6% three prior anti-TNF drugs.

The most common nonbiologic DMARD used was methotrexate (52%), with some patients receiving up to seven DMARDs.

According to European League Against Rheumatism criteria, 43% of patients showed a "moderate" response to rituximab after 6 months, despite all their prior therapies, with 16% even achieving a "good" response. However, the remaining 41% did not respond to treatment with rituximab.

The mean 28-joint disease activity score (DAS28) at baseline was 6.2 for the whole cohort, which fell to 4.8 at 6 months, a mean change of –1.4. Health Assessment Questionnaire (HAQ) scores also fell, by a mean of –0.1 over the same time period, indicating improved physical function.

Patients who had not received prior anti-TNF therapy (16% of the cohort) appeared to fare better than those who had received such treatment before rituximab, with a mean change in DAS28 of –1.7 compared with –1.3 for anti-TNF failures (P = .05).

The second analysis, presented at a poster session, looked more specifically for baseline factors that might predict which patients were likely to have a better response than others to rituximab.

The analysis involved 463 patients and found that those with higher baseline DAS28 scores were significantly more likely to respond to rituximab than those with lower DAS28 scores.

In addition, rheumatoid factor–positive patients were more likely to achieve disease remission than seronegative patients, but those with higher functional disability (that is, higher HAQ scores) or higher baseline DAS28 scores were less likely to achieve remission by 6 months.

"Rituximab is proven effective in the routine management of RA patients," Ms. Soliman commented. "Response to rituximab was influenced by baseline disease activity and baseline physical function."

The BSRBR is funded by a grant from the BSR. The BSR receives funding from Abbott Laboratories, Biovitrum/SOBI, Merck Sharp & Dohme, Pfizer, Roche, and UCB. This income finances a separate contract between the BSR and the University of Manchester that provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Ms. Soliman said she had no relevant financial disclosures.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.