Rheumatoid Arthritis

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

Major Finding: The RA and diabetes cohorts both had a 1.7 increased incidence rate ratio (IRR) of MI, compared with the general population.

Data Source: A large, population-based study of the incidence of new-onset rheumatoid arthritis, diabetes, and myocardial infarction using Danish patient registry information covering a 10-year period.

Disclosures: The study was supported by an unrestricted grant from the Danish Rheumatism Association. The authors disclosed having no conflicts of interest.

The cardiovascular risk in rheumatoid arthritis is comparable to that of diabetes, a large Danish study has shown.

Further, the risk of myocardial infarction (MI) in rheumatoid arthritis patients corresponds to that observed in the general population of individuals without the musculoskeletal condition who are, on average, 10 years older and does not appear to be affected by the duration of drug treatment for the disease, Dr. Jesper Lindhardsen of Gentofte University Hospital in Copenhagen, and colleagues reported.

Using nationwide registers encompassing the entire Danish population older than 16 years, the investigators identified individuals with new-onset rheumatoid arthritis (RA), new-onset diabetes, and new MI during a 10-year period, excluding individuals with prior disease and incomplete data entries from the full cohort of 4,311,022 subjects, they wrote.

During the 10-year study period, 9,921 individuals developed RA and 129,659 developed diabetes. Compared with the diabetes patients, “RA patients were more often women, used less cardioprotective medications, and had less comorbidity, whereas age was similar in the two groups,” they reported.

Regarding cardiovascular outcomes, 265 of the RA patients and 3,948 of the diabetes patients had new MI, representing in both cohorts a 1.7 increased incidence rate ratio (IRR) of MI in a fully adjusted model compared with the general population in which 75,870 individuals had new myocardial infarctions. The IRR among patients with both RA and diabetes was 2.6, “which roughly equaled the predicted additive risk for the two separate diseases, they wrote (Ann. Rheum. Dis. 2011;70:929–34).

The investigators conducted a nested case-control study that corroborated the comparable risk of MI in the RA and diabetes patients. The findings demonstrated that the increased risk in these groups was independent of treatment duration within the time frame of the current study, they wrote.

Stratified by gender, the MI risk estimates did not differ between women and men in the RA group. In the diabetes patients, however, women were at significantly higher risk than men for the adverse cardiovascular outcome, the authors wrote. An age-dependent pattern of MI risk was also observed. Specifically, among women with RA and diabetes, respectively, the risk of MI in those younger than 50 years old was 5.5 and 5.9 times that observed in the age-matched reference group, they reported. Additionally, for women between 50 and 65 years of age, the IRRs were 1.7 and 2.6 for RA and diabetes patients, respectively.

The age-stratified patterns observed in men were different, the authors stated, noting that “the IRRs in the two oldest age groups were comparable, and even tended to be slightly higher in the 50-65 years age group of RA patients compared to the same-aged [diabetes] patients.” And while the youngest men with RA had a markedly raised IRR, diabetes patients in the same age stratum had a significantly higher risk, with an IRR of 4.9 compared with 2.1, they said.

In a fully adjusted regression model in which the IRRs for MI in RA patients were calculated according to 10-year subject age intervals, “RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older,” the authors reported.

Although the study has several limitations, including the identification of RA patients based on dispensed prescriptions and diagnosis versus the 1987 American College of Rheumatology criteria, the reliance on the use of glucose-lowering drugs as a proxy for diabetes, and the lack of information about classic cardiovascular risk factors, “the results corroborate and expand previous findings in this area of research and indicate that patients with RA should be considered for more aggressive primary [cardiovascular disease] prevention,” the authors stressed.

In an accompanying editorial, Dr. Michael T. Nurmohamed and Dr. George Kitas of VU University Medical Centre in Amsterdam wrote that the findings of the current study should put to bed any doubt or debate about an enhanced cardiovascular risk in RA. “Importantly, they also provide further evidence that the cardiovascular risk in RA is broadly similar to that of contemporarily managed diabetes,” they stated. The results of the study, as well as the success of cardiovascular risk management in diabetes provides a clear incentive to identify and actively manage, if necessary, cardiovascular risk in all RA patients as part of quality routine rheumatological practice” (Ann. Rheum. Dis. 2011;70:881–3).

The study was sponsored by an unrestricted grant from the Danish Rheumatism Association. The authors of the study and the accompanying editorial reported having no conflicts of interest.

'RA patients had the same, or higher, risk of MI as control subjects who were, on average, 10 years older.'

Source DR. LINDHARDSEN

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to study results reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10 mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker Said in an interview.”

“The existing strategies leave room for improvement, especially for the number of patients who reach remission,” said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study's rationale. “Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy.”

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trial was designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

The investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

Time to sustained remission was 6 months in the experimental group and 11 months in the control group.

Source DR. BAKKER

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to study results reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10 mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker Said in an interview.”

“The existing strategies leave room for improvement, especially for the number of patients who reach remission,” said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study's rationale. “Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy.”

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trial was designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

The investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

Time to sustained remission was 6 months in the experimental group and 11 months in the control group.

Source DR. BAKKER

The addition of low-dose prednisone to a methotrexate-based, tight-control strategy leads to better outcomes in early rheumatoid arthritis, according to study results reported by Marije F. Bakker, Ph.D.

Compared with patients who received methotrexate (MTX) with placebo, those receiving MTX with 10 mg/day prednisone had better control of their disease and less erosive damage to their joints, Dr. Bakker Said in an interview.”

“The existing strategies leave room for improvement, especially for the number of patients who reach remission,” said Dr. Bakker of University Medical Center Utrecht (the Netherlands) in explaining the study's rationale. “Besides, it is important to determine which strategy steps are useful in the tight-control treatment strategies. Also, it is important to decide at which moment early in the treatment of [rheumatoid arthritis] medication should be added to the strategy.”

The CAMERA-II (Computer-Assisted Management of Early Rheumatoid Arthritis–II) trial was designed specifically to test the hypothesis that the addition of prednisone to a tight-control strategy of early RA using disease-modifying antirheumatic drugs would result in better disease control.

In the randomized, double-blind, placebo-controlled trial, 117 patients received MTX plus prednisone and 119 received MTX with placebo. All patients had early RA, with an onset less than 1 year before enrollment. Patients were at least 18 years old and had no previous DMARD therapy.

Patients were excluded from the trial if they had major comorbidities such as malignancies or severe diabetes mellitus; abnormal liver or kidney function; leukopenia or thrombocytopenia; evidence of drug or alcohol abuse; treatment with cytotoxic or immunosuppressive drugs within 3 months of the study; or osteoporotic vertebral fractures.

The investigators tailored the MTX treatment to each patient with the goal of achieving remission. If patients did not achieve remission with the maximum tolerable oral MTX dose, investigators first switched the patient to subcutaneous MTX and then added adalimumab to the regimen.

After 2 years, patients in the MTX plus prednisone group had significantly less radiographically confirmed erosive joint damage, as measured by their Sharp/van der Heijde scores. Patients on the MTX with prednisone regimen had significantly lower scores on the DAS28 (Disease Activity Score using a 28-joint count) questionnaire, and lower disability scores on the HAQ (Health Assessment Questionnaire).

A significantly lower proportion of patients in the experimental group required biologic treatment, compared with those on placebo (14% vs. 36%). The time to sustained remission was 6 months in the experimental group and 11 months in the control group, a significant difference. In addition, patients in the experimental group appeared to be somewhat more likely to achieve sustained remission, although this result did not achieve statistical significance (72% vs. 61%; P = .09).

Rates of adverse events were similar (29% in the MTX-prednisone group and 35% in the MTX-placebo group).

The trial was supported by the University Medical Center Utrecht and by Abbott. Dr. Bakker stated that she had no relevant financial disclosures.

Time to sustained remission was 6 months in the experimental group and 11 months in the control group.

Source DR. BAKKER

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.”

For patients with a history of myo-cardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

“These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required,” concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [(doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment “should be as short as possible,” the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57–3.86 for death/MI at day 1–7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14–30 days with celecoxib.

The risk associated with ibuprofen was lower than the risk associated with the two cyclooxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac.

There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The authors said they had no relevant financial disclosures.

For patients with a history of myo-cardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

“These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required,” concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [(doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment “should be as short as possible,” the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57–3.86 for death/MI at day 1–7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14–30 days with celecoxib.

The risk associated with ibuprofen was lower than the risk associated with the two cyclooxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac.

There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The authors said they had no relevant financial disclosures.

For patients with a history of myo-cardial infarction, any length of treatment with nonsteroidal anti-inflammatory drugs poses an unacceptably high risk for death or recurrent heart attack, based on findings from a Danish study using hospital and pharmacy registry data.

The risk elevation began during the first week of therapy and continued throughout the course of treatment, with some differences in the magnitude of risk between NSAIDs.

“These results challenge the view that NSAIDs are not harmful during short-term [1-week] treatment and indicate that a revision of current recommendations regarding NSAID treatment in patients with established cardiovascular disease is required,” concluded Anne-Marie Schjerning of the department of cardiology, Copenhagen University Hospital in Gentofte, Denmark, and her coauthors. (Circulation 2011 May 9 [(doi: 0.1161/CIRCULATIONAHA.110.004671]).

The significant increase in death and recurrent myocardial infarction associated with the use of NSAIDs in a study of people with a history of myocardial infarction indicates that current recommendations regarding NSAID use in patients with cardiovascular disease need to be revised, the study authors concluded.

Although international guidelines state that NSAID use should be discouraged in people with established cardiovascular disease, they say that if such use is unavoidable, the duration of NSAID treatment “should be as short as possible,” the authors pointed out.

The investigators conducted the study to address the paucity of information on the association between the duration of treatment with NSAIDs and the risk of cardiovascular disease, in this population of patients. Of the 83,675 people aged 30 years and older who had had their first MI from 1997 through 2006 identified in the national registries (mean age, 68 years), 42% had received NSAIDs.

Overall, treatment with NSAIDs was associated with a 45% greater risk of death/recurrent MI during the first 7 days of treatment, which persisted and was increased by 65% over a 30- to 90-day period of treatment.

The greatest risk identified was with diclofenac (hazard ratio, 3.26; 95% confidence interval, 2.57–3.86 for death/MI at day 1–7 of treatment). Diclofenac is available over the counter in many countries, the authors noted.

A significant increase in risk was seen after 1 week of treatment with ibuprofen, in the first week of treatment with rofecoxib (which has been withdrawn from the market), and after 14–30 days with celecoxib.

The risk associated with ibuprofen was lower than the risk associated with the two cyclooxygenase-2 (COX-2) selective inhibitors, rofecoxib and celecoxib, and it was lower than the risk associated with the use of diclofenac.

There was no increased risk of death or recurrent MI associated with naproxen for the entire treatment duration, which exceeded 90 days in some cases. However, naproxen has been associated with an increased risk of GI bleeding, compared with rofecoxib, in one study, the authors noted.

The authors said they had no relevant financial disclosures.

Major Finding: Patients given rituximab for refractory RA are at “modest” risk of developing progressive multifocal leukoencephalopathy, with an estimated incidence of 1 case of PML per 25,000 drug exposures.

Data Source: Case studies of five RA patients who developed PML after receiving rituximab.

Disclosures: This study was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Allergy and Infectious Diseases. Dr. Clifford and his associates reported ties to Bavarian Nordic, Biogen Idec, Bristol-Myers Squibb, Genentech (maker of rituximab), Genzyme, GlaxoSmithKline, Lilly, Millennium, NeurogesX, Novartis, Pfizer, Schering-Plough, Tibotec, and Wyeth.

Physicians considering the use of rituximab treatment of rheumatic diseases including rheumatoid arthritis should be aware that there is “a potential, albeit modest, risk of developing progressive multifocal leukoencephalopathy,” a study has shown.

In addition, rheumatology patients who are already taking the drug should undergo “aggressive evaluation of new and progressing neurologic deficits … to allow early diagnosis” of progressive multifocal leukoencephalopathy (PML), said Dr. David B. Clifford, professor of neurology and medicine at Washington University in St. Louis, and his associates.

PML is a serious, often fatal demyelinating infection of the brain, usually caused by reactivation of latent JC virus in people who are immunocompromised. It also has been reported as a complication of treatment with monoclonal antibodies such as natalizumab and efalizumab, among patients taking the drugs for disorders including multiple sclerosis, inflammatory bowel disease, and chronic plaque psoriasis.

The mechanism by which these agents facilitate the development of PML is not yet known, but it is presumed that some suppressive effect they exert on the immune system allows latent JC virus to reactivate. Primary JC virus infection usually occurs unnoticed during childhood and is very widespread; most adults are seropositive for JC virus, and many carry latent virus in kidney epithelial cells, lymphoid tissues, bone marrow, and possibly the brain.

“Until very recently, treatment of RA with rituximab had not been associated with development of PML,” the investigators wrote. There was one case reported in 2009, but that “was complicated by a history of malignancy that had been treated with chemotherapy and irradiation a short time before PML onset,” so the connection with rituximab was unclear, they noted.

Dr. Clifford and his colleagues now report four additional cases of PML in RA patients treated with rituximab. To characterize the disorder in this patient population, they summarized their findings along with those for the previously reported case.

All of the patients were women aged 51–73 years who had moderate to severe RA of at least 3 years' duration. All began taking rituximab after failing to respond adequately to other interventions including methotrexate, other biologics, or corticosteroids.

In all cases, rituximab was given at the recommended dose for refractory RA: Each course comprised two 1,000-mg infusions administered 2 weeks apart. Two patients received only a single course, and the maximal number of courses was five. In two cases, patients may have been at increased risk of PML because of cancer. One woman had a history of breast cancer treated with surgery and chemotherapy; the other was the previously reported case in which the patient developed superficial squamous cell carcinoma of the oropharynx and received chemotherapy and irradiation after rituximab had been administered.

Symptom onset occurred at 5–7 months after a rituximab infusion in three cases. This timing is “interesting” because it occurs during the process of immune reconstitution, rather than earlier, when CD20 cells reach their nadir.

In a fourth case, PML onset was delayed until 16 months after rituximab infusion. However this also proved to be during immune reconstitution, as this patient had an unusually prolonged interval of CD-cell suppression. This suppression “only began to normalize after PML onset, when a clear immune reconstitution inflammatory syndrome (IRIS) was well documented on MR scans,” the investigators said.

It appears that the immune reconstitution inflammatory syndrome may often complicate rituximab-associated PML, as it developed in three of these five cases. “This factor is critical for clinicians, since it impacts diagnosis and management,” they added.

These five patients presented with a variety of central nervous system symptoms including dysesthesias, ataxia, dysphasia, cognitive decline, focal dystonic tremor, and segmental myoclonus. JC virus DNA frequently was not detectable in the cerebrospinal fluid at presentation, “and was found only after repeated lumbar punctures as the disease progressed.” In fact, one case required a brain biopsy to confirm PML.

Genentech, the maker of rituximab, estimates that these five cases of PML occurred against a background of approximately 129,000 exposures among RA patients. This puts the incidence of rituximab-associated PML at 1 in 25,000 exposed RA patients, Dr. Clifford and his associates said (Arch. Neurol. 2011 May 9 [doi:10.1001/archneurol.2011.103]).

This may be an underestimate because it's likely that more patients have not been accurately diagnosed or reported to the company, they added.

This “modest” incidence is lower than that reported for natalizumab-associated PML (1 in 1,000 patients exposed for more than 2 years) or for efalizumab-associated PML (1 in 400 exposed patients).

The need for effective treatments of rituximab-associated PML is “urgent.” Antiviral therapy has not been shown to be effective. Some clinicians still try using cytosine arabinoside and cidofovir, “in spite of significant evidence that they are not effective.”

Mefloquine hydrochloride has shown in vitro activity against JC virus and was used “in several of our cases,” but failed to show efficacy in a recent clinical trial. “Similarly, clinicians continue to prescribe mirtazapine on a theoretical basis, related to its potential efficacy in blocking serotonin receptors used for viral entry, despite absence of documented clinical efficacy,” they said.

Plasma exchange has become standard practice for natalizumab-associated PML, but it is only likely to speed immune recovery in RA patients taking rituximab if PML is discovered shortly after an infusion of the drug.

If patients develop immune reconstitution inflammatory syndrome, that “provides an additional potential therapeutic avenue.” High-dose corticosteroid pulses – “often 1 g of IV methylprednisolone daily for 5 days, which is repeated if symptoms respond and then recur” – may halt neurologic decline and initiate recovery. “Physicians should be aware that this may be required even when the CD20 count suggests ongoing immune compromise” from the rituximab therapy, they added.

Major Finding: Patients given rituximab for refractory RA are at “modest” risk of developing progressive multifocal leukoencephalopathy, with an estimated incidence of 1 case of PML per 25,000 drug exposures.

Data Source: Case studies of five RA patients who developed PML after receiving rituximab.

Disclosures: This study was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Allergy and Infectious Diseases. Dr. Clifford and his associates reported ties to Bavarian Nordic, Biogen Idec, Bristol-Myers Squibb, Genentech (maker of rituximab), Genzyme, GlaxoSmithKline, Lilly, Millennium, NeurogesX, Novartis, Pfizer, Schering-Plough, Tibotec, and Wyeth.

Physicians considering the use of rituximab treatment of rheumatic diseases including rheumatoid arthritis should be aware that there is “a potential, albeit modest, risk of developing progressive multifocal leukoencephalopathy,” a study has shown.

In addition, rheumatology patients who are already taking the drug should undergo “aggressive evaluation of new and progressing neurologic deficits … to allow early diagnosis” of progressive multifocal leukoencephalopathy (PML), said Dr. David B. Clifford, professor of neurology and medicine at Washington University in St. Louis, and his associates.

PML is a serious, often fatal demyelinating infection of the brain, usually caused by reactivation of latent JC virus in people who are immunocompromised. It also has been reported as a complication of treatment with monoclonal antibodies such as natalizumab and efalizumab, among patients taking the drugs for disorders including multiple sclerosis, inflammatory bowel disease, and chronic plaque psoriasis.

The mechanism by which these agents facilitate the development of PML is not yet known, but it is presumed that some suppressive effect they exert on the immune system allows latent JC virus to reactivate. Primary JC virus infection usually occurs unnoticed during childhood and is very widespread; most adults are seropositive for JC virus, and many carry latent virus in kidney epithelial cells, lymphoid tissues, bone marrow, and possibly the brain.

“Until very recently, treatment of RA with rituximab had not been associated with development of PML,” the investigators wrote. There was one case reported in 2009, but that “was complicated by a history of malignancy that had been treated with chemotherapy and irradiation a short time before PML onset,” so the connection with rituximab was unclear, they noted.

Dr. Clifford and his colleagues now report four additional cases of PML in RA patients treated with rituximab. To characterize the disorder in this patient population, they summarized their findings along with those for the previously reported case.

All of the patients were women aged 51–73 years who had moderate to severe RA of at least 3 years' duration. All began taking rituximab after failing to respond adequately to other interventions including methotrexate, other biologics, or corticosteroids.

In all cases, rituximab was given at the recommended dose for refractory RA: Each course comprised two 1,000-mg infusions administered 2 weeks apart. Two patients received only a single course, and the maximal number of courses was five. In two cases, patients may have been at increased risk of PML because of cancer. One woman had a history of breast cancer treated with surgery and chemotherapy; the other was the previously reported case in which the patient developed superficial squamous cell carcinoma of the oropharynx and received chemotherapy and irradiation after rituximab had been administered.

Symptom onset occurred at 5–7 months after a rituximab infusion in three cases. This timing is “interesting” because it occurs during the process of immune reconstitution, rather than earlier, when CD20 cells reach their nadir.

In a fourth case, PML onset was delayed until 16 months after rituximab infusion. However this also proved to be during immune reconstitution, as this patient had an unusually prolonged interval of CD-cell suppression. This suppression “only began to normalize after PML onset, when a clear immune reconstitution inflammatory syndrome (IRIS) was well documented on MR scans,” the investigators said.

It appears that the immune reconstitution inflammatory syndrome may often complicate rituximab-associated PML, as it developed in three of these five cases. “This factor is critical for clinicians, since it impacts diagnosis and management,” they added.

These five patients presented with a variety of central nervous system symptoms including dysesthesias, ataxia, dysphasia, cognitive decline, focal dystonic tremor, and segmental myoclonus. JC virus DNA frequently was not detectable in the cerebrospinal fluid at presentation, “and was found only after repeated lumbar punctures as the disease progressed.” In fact, one case required a brain biopsy to confirm PML.

Genentech, the maker of rituximab, estimates that these five cases of PML occurred against a background of approximately 129,000 exposures among RA patients. This puts the incidence of rituximab-associated PML at 1 in 25,000 exposed RA patients, Dr. Clifford and his associates said (Arch. Neurol. 2011 May 9 [doi:10.1001/archneurol.2011.103]).

This may be an underestimate because it's likely that more patients have not been accurately diagnosed or reported to the company, they added.

This “modest” incidence is lower than that reported for natalizumab-associated PML (1 in 1,000 patients exposed for more than 2 years) or for efalizumab-associated PML (1 in 400 exposed patients).

The need for effective treatments of rituximab-associated PML is “urgent.” Antiviral therapy has not been shown to be effective. Some clinicians still try using cytosine arabinoside and cidofovir, “in spite of significant evidence that they are not effective.”

Mefloquine hydrochloride has shown in vitro activity against JC virus and was used “in several of our cases,” but failed to show efficacy in a recent clinical trial. “Similarly, clinicians continue to prescribe mirtazapine on a theoretical basis, related to its potential efficacy in blocking serotonin receptors used for viral entry, despite absence of documented clinical efficacy,” they said.

Plasma exchange has become standard practice for natalizumab-associated PML, but it is only likely to speed immune recovery in RA patients taking rituximab if PML is discovered shortly after an infusion of the drug.

If patients develop immune reconstitution inflammatory syndrome, that “provides an additional potential therapeutic avenue.” High-dose corticosteroid pulses – “often 1 g of IV methylprednisolone daily for 5 days, which is repeated if symptoms respond and then recur” – may halt neurologic decline and initiate recovery. “Physicians should be aware that this may be required even when the CD20 count suggests ongoing immune compromise” from the rituximab therapy, they added.

Major Finding: Patients given rituximab for refractory RA are at “modest” risk of developing progressive multifocal leukoencephalopathy, with an estimated incidence of 1 case of PML per 25,000 drug exposures.

Data Source: Case studies of five RA patients who developed PML after receiving rituximab.

Disclosures: This study was supported by the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the National Institute of Allergy and Infectious Diseases. Dr. Clifford and his associates reported ties to Bavarian Nordic, Biogen Idec, Bristol-Myers Squibb, Genentech (maker of rituximab), Genzyme, GlaxoSmithKline, Lilly, Millennium, NeurogesX, Novartis, Pfizer, Schering-Plough, Tibotec, and Wyeth.

Physicians considering the use of rituximab treatment of rheumatic diseases including rheumatoid arthritis should be aware that there is “a potential, albeit modest, risk of developing progressive multifocal leukoencephalopathy,” a study has shown.

In addition, rheumatology patients who are already taking the drug should undergo “aggressive evaluation of new and progressing neurologic deficits … to allow early diagnosis” of progressive multifocal leukoencephalopathy (PML), said Dr. David B. Clifford, professor of neurology and medicine at Washington University in St. Louis, and his associates.

PML is a serious, often fatal demyelinating infection of the brain, usually caused by reactivation of latent JC virus in people who are immunocompromised. It also has been reported as a complication of treatment with monoclonal antibodies such as natalizumab and efalizumab, among patients taking the drugs for disorders including multiple sclerosis, inflammatory bowel disease, and chronic plaque psoriasis.

The mechanism by which these agents facilitate the development of PML is not yet known, but it is presumed that some suppressive effect they exert on the immune system allows latent JC virus to reactivate. Primary JC virus infection usually occurs unnoticed during childhood and is very widespread; most adults are seropositive for JC virus, and many carry latent virus in kidney epithelial cells, lymphoid tissues, bone marrow, and possibly the brain.

“Until very recently, treatment of RA with rituximab had not been associated with development of PML,” the investigators wrote. There was one case reported in 2009, but that “was complicated by a history of malignancy that had been treated with chemotherapy and irradiation a short time before PML onset,” so the connection with rituximab was unclear, they noted.

Dr. Clifford and his colleagues now report four additional cases of PML in RA patients treated with rituximab. To characterize the disorder in this patient population, they summarized their findings along with those for the previously reported case.

All of the patients were women aged 51–73 years who had moderate to severe RA of at least 3 years' duration. All began taking rituximab after failing to respond adequately to other interventions including methotrexate, other biologics, or corticosteroids.

In all cases, rituximab was given at the recommended dose for refractory RA: Each course comprised two 1,000-mg infusions administered 2 weeks apart. Two patients received only a single course, and the maximal number of courses was five. In two cases, patients may have been at increased risk of PML because of cancer. One woman had a history of breast cancer treated with surgery and chemotherapy; the other was the previously reported case in which the patient developed superficial squamous cell carcinoma of the oropharynx and received chemotherapy and irradiation after rituximab had been administered.

Symptom onset occurred at 5–7 months after a rituximab infusion in three cases. This timing is “interesting” because it occurs during the process of immune reconstitution, rather than earlier, when CD20 cells reach their nadir.

In a fourth case, PML onset was delayed until 16 months after rituximab infusion. However this also proved to be during immune reconstitution, as this patient had an unusually prolonged interval of CD-cell suppression. This suppression “only began to normalize after PML onset, when a clear immune reconstitution inflammatory syndrome (IRIS) was well documented on MR scans,” the investigators said.

It appears that the immune reconstitution inflammatory syndrome may often complicate rituximab-associated PML, as it developed in three of these five cases. “This factor is critical for clinicians, since it impacts diagnosis and management,” they added.

These five patients presented with a variety of central nervous system symptoms including dysesthesias, ataxia, dysphasia, cognitive decline, focal dystonic tremor, and segmental myoclonus. JC virus DNA frequently was not detectable in the cerebrospinal fluid at presentation, “and was found only after repeated lumbar punctures as the disease progressed.” In fact, one case required a brain biopsy to confirm PML.

Genentech, the maker of rituximab, estimates that these five cases of PML occurred against a background of approximately 129,000 exposures among RA patients. This puts the incidence of rituximab-associated PML at 1 in 25,000 exposed RA patients, Dr. Clifford and his associates said (Arch. Neurol. 2011 May 9 [doi:10.1001/archneurol.2011.103]).

This may be an underestimate because it's likely that more patients have not been accurately diagnosed or reported to the company, they added.

This “modest” incidence is lower than that reported for natalizumab-associated PML (1 in 1,000 patients exposed for more than 2 years) or for efalizumab-associated PML (1 in 400 exposed patients).

The need for effective treatments of rituximab-associated PML is “urgent.” Antiviral therapy has not been shown to be effective. Some clinicians still try using cytosine arabinoside and cidofovir, “in spite of significant evidence that they are not effective.”

Mefloquine hydrochloride has shown in vitro activity against JC virus and was used “in several of our cases,” but failed to show efficacy in a recent clinical trial. “Similarly, clinicians continue to prescribe mirtazapine on a theoretical basis, related to its potential efficacy in blocking serotonin receptors used for viral entry, despite absence of documented clinical efficacy,” they said.

Plasma exchange has become standard practice for natalizumab-associated PML, but it is only likely to speed immune recovery in RA patients taking rituximab if PML is discovered shortly after an infusion of the drug.

If patients develop immune reconstitution inflammatory syndrome, that “provides an additional potential therapeutic avenue.” High-dose corticosteroid pulses – “often 1 g of IV methylprednisolone daily for 5 days, which is repeated if symptoms respond and then recur” – may halt neurologic decline and initiate recovery. “Physicians should be aware that this may be required even when the CD20 count suggests ongoing immune compromise” from the rituximab therapy, they added.

To date, no new significant safety signals associated with rituximab therapy in patients with severe rheumatoid arthritis who also have lung disease have been identified in an ongoing observational study of such patients, according to Dr. Shouvik Dass.

Overall, the incidence of serious infections has been low and is about what would be expected in these patients, who already have significant comorbidity because of longstanding RA and preexisting lung disease, said Dr. Dass, of the department of rheumatology, University of Leeds (England).

Because interstitial lung disease and various other lung diseases are more common among patients with RA, they may be considered contraindications to treatment with anti–tumor necrosis factor therapy, because of reports that the anti-TNF agents may cause, or at least may be associated with, major deteriorations in interstitial lung disease. Although these data are not definitive, as a result, the use of rituximab – a CD20-directed cytolytic antibody – may be increasing among patients with RA and pulmonary disease, said Dr. Dass.

“The effect of biologic therapies as a whole on lung disease is not completely clear,” he said in an interview. He also referred to data – mostly case reports– in the hematologic literature associating rituximab with worsening lung disease.

He and his associates reviewed the records of 67 patients with RA and concomitant lung disease who were treated with rituximab between 2004 and 2010 at their center, which he said has one of the largest single cohorts of RA patients treated with rituximab. The patients' mean age was 60 years and most (56) were female. The most common pulmonary diagnosis was interstitial lung disease (ILD) in 48 patients; 14 patients had chronic obstructive pulmonary disease (COPD), and 5 patients had bronchiectasis; 2 patients also had had a previous pulmonary empyema.

All patients received two infusions of 1,000 mg rituximab with methylprednisolone per course, which was repeated when RA became active again, at intervals of no less than 6 months. Half of the patients received at least two treatment cycles.

Over a median of about 2 years of follow-up (the range was about 8 months to 6.5 years) after treatment with rituximab, there were three deaths among these patients: 2 of the 48 patients with ILD and 1 of the 14 patients with COPD. The patient with COPD died of an infective COPD exacerbation 12 months after the third cycle of rituximab. One of the patients with ILD died of pneumonia and possible acute progression of ILD, Dr. Dass said, noting that clinical and CT changes attributable to either condition were observed 4 weeks after the patient had been treated with the first cycle of rituximab. Suicide was the cause of death in the second patient with ILD, 3 months after treatment with the first course of rituximab. Another three patients had a single episode of serious respiratory tract infection, which required hospital admission or treatment with intravenous antibiotics.

Based on these cases, there were no definite new significant safety signals that were observed “beyond that which might be expected in this group of patients with longstanding severe RA and concomitant lung disease,” Dr. Dass said.

However, he pointed out that the one death caused by respiratory deterioration was temporally related to rituximab therapy.

“B-cell depletion is now an important therapy for RA, and therefore this study aims to add insight into the safety and practical usage of rituximab,” he noted in the interview. “We hope to encourage ongoing review and follow-up of such patients.”

In the United States, rituximab is marketed as Rituxan by Genentech, a member of the Roche Group, and is a registered trademark of Biogen Idec.

Dr. Dass and two of his six coauthors disclosed that they are consultants for Roche. Dr. Dass received an award from EULAR for this research.

To date, no new significant safety signals associated with rituximab therapy in patients with severe rheumatoid arthritis who also have lung disease have been identified in an ongoing observational study of such patients, according to Dr. Shouvik Dass.

Overall, the incidence of serious infections has been low and is about what would be expected in these patients, who already have significant comorbidity because of longstanding RA and preexisting lung disease, said Dr. Dass, of the department of rheumatology, University of Leeds (England).

Because interstitial lung disease and various other lung diseases are more common among patients with RA, they may be considered contraindications to treatment with anti–tumor necrosis factor therapy, because of reports that the anti-TNF agents may cause, or at least may be associated with, major deteriorations in interstitial lung disease. Although these data are not definitive, as a result, the use of rituximab – a CD20-directed cytolytic antibody – may be increasing among patients with RA and pulmonary disease, said Dr. Dass.

“The effect of biologic therapies as a whole on lung disease is not completely clear,” he said in an interview. He also referred to data – mostly case reports– in the hematologic literature associating rituximab with worsening lung disease.

He and his associates reviewed the records of 67 patients with RA and concomitant lung disease who were treated with rituximab between 2004 and 2010 at their center, which he said has one of the largest single cohorts of RA patients treated with rituximab. The patients' mean age was 60 years and most (56) were female. The most common pulmonary diagnosis was interstitial lung disease (ILD) in 48 patients; 14 patients had chronic obstructive pulmonary disease (COPD), and 5 patients had bronchiectasis; 2 patients also had had a previous pulmonary empyema.

All patients received two infusions of 1,000 mg rituximab with methylprednisolone per course, which was repeated when RA became active again, at intervals of no less than 6 months. Half of the patients received at least two treatment cycles.

Over a median of about 2 years of follow-up (the range was about 8 months to 6.5 years) after treatment with rituximab, there were three deaths among these patients: 2 of the 48 patients with ILD and 1 of the 14 patients with COPD. The patient with COPD died of an infective COPD exacerbation 12 months after the third cycle of rituximab. One of the patients with ILD died of pneumonia and possible acute progression of ILD, Dr. Dass said, noting that clinical and CT changes attributable to either condition were observed 4 weeks after the patient had been treated with the first cycle of rituximab. Suicide was the cause of death in the second patient with ILD, 3 months after treatment with the first course of rituximab. Another three patients had a single episode of serious respiratory tract infection, which required hospital admission or treatment with intravenous antibiotics.

Based on these cases, there were no definite new significant safety signals that were observed “beyond that which might be expected in this group of patients with longstanding severe RA and concomitant lung disease,” Dr. Dass said.

However, he pointed out that the one death caused by respiratory deterioration was temporally related to rituximab therapy.

“B-cell depletion is now an important therapy for RA, and therefore this study aims to add insight into the safety and practical usage of rituximab,” he noted in the interview. “We hope to encourage ongoing review and follow-up of such patients.”

In the United States, rituximab is marketed as Rituxan by Genentech, a member of the Roche Group, and is a registered trademark of Biogen Idec.

Dr. Dass and two of his six coauthors disclosed that they are consultants for Roche. Dr. Dass received an award from EULAR for this research.

To date, no new significant safety signals associated with rituximab therapy in patients with severe rheumatoid arthritis who also have lung disease have been identified in an ongoing observational study of such patients, according to Dr. Shouvik Dass.

Overall, the incidence of serious infections has been low and is about what would be expected in these patients, who already have significant comorbidity because of longstanding RA and preexisting lung disease, said Dr. Dass, of the department of rheumatology, University of Leeds (England).

Because interstitial lung disease and various other lung diseases are more common among patients with RA, they may be considered contraindications to treatment with anti–tumor necrosis factor therapy, because of reports that the anti-TNF agents may cause, or at least may be associated with, major deteriorations in interstitial lung disease. Although these data are not definitive, as a result, the use of rituximab – a CD20-directed cytolytic antibody – may be increasing among patients with RA and pulmonary disease, said Dr. Dass.

“The effect of biologic therapies as a whole on lung disease is not completely clear,” he said in an interview. He also referred to data – mostly case reports– in the hematologic literature associating rituximab with worsening lung disease.

He and his associates reviewed the records of 67 patients with RA and concomitant lung disease who were treated with rituximab between 2004 and 2010 at their center, which he said has one of the largest single cohorts of RA patients treated with rituximab. The patients' mean age was 60 years and most (56) were female. The most common pulmonary diagnosis was interstitial lung disease (ILD) in 48 patients; 14 patients had chronic obstructive pulmonary disease (COPD), and 5 patients had bronchiectasis; 2 patients also had had a previous pulmonary empyema.

All patients received two infusions of 1,000 mg rituximab with methylprednisolone per course, which was repeated when RA became active again, at intervals of no less than 6 months. Half of the patients received at least two treatment cycles.

Over a median of about 2 years of follow-up (the range was about 8 months to 6.5 years) after treatment with rituximab, there were three deaths among these patients: 2 of the 48 patients with ILD and 1 of the 14 patients with COPD. The patient with COPD died of an infective COPD exacerbation 12 months after the third cycle of rituximab. One of the patients with ILD died of pneumonia and possible acute progression of ILD, Dr. Dass said, noting that clinical and CT changes attributable to either condition were observed 4 weeks after the patient had been treated with the first cycle of rituximab. Suicide was the cause of death in the second patient with ILD, 3 months after treatment with the first course of rituximab. Another three patients had a single episode of serious respiratory tract infection, which required hospital admission or treatment with intravenous antibiotics.

Based on these cases, there were no definite new significant safety signals that were observed “beyond that which might be expected in this group of patients with longstanding severe RA and concomitant lung disease,” Dr. Dass said.

However, he pointed out that the one death caused by respiratory deterioration was temporally related to rituximab therapy.

“B-cell depletion is now an important therapy for RA, and therefore this study aims to add insight into the safety and practical usage of rituximab,” he noted in the interview. “We hope to encourage ongoing review and follow-up of such patients.”

In the United States, rituximab is marketed as Rituxan by Genentech, a member of the Roche Group, and is a registered trademark of Biogen Idec.

Dr. Dass and two of his six coauthors disclosed that they are consultants for Roche. Dr. Dass received an award from EULAR for this research.

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.

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapåå Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%).

Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

“The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor” in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001).

The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapåå Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%).

Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

“The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor” in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001).

The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

Unaffected first-degree relatives of patients with rheumatoid arthritis have an increased number of known risk factors for RA, compared with unaffected controls. However, the prevalence of risk factors in relatives does not equal that seen in patients, according to Dr. Lotta Ljung, senior consultant rheumatologist at Umeå (Sweden) University Hospital.

For example, the unaffected relatives had a significantly greater prevalence of anti–CCP (cyclic citrullinated peptide) protein IgG, IgA, and IgM antibody isotypes and rheumatoid factors of IgM and IgA isotypes than did the controls, Dr. Ljung said at the meeting, noting that she was not involved in the research. She gave the presentation for researcher Lisbeth Ärlestig, Ph.D., a student at Umeå University, the scheduled presenter who was unable to attend.

The findings could lead to better understanding of the factors that affect rheumatoid arthritis (RA) development. Because the etiology of RA is still unknown and autoantibodies are common in patients affected with RA (and the anti-CCP antibodies discussed appear to be involved in the pathogenesis of the disease), it is of interest to analyze the prevalence, concentrations, and pattern of antibodies in first-degree relatives in multicase families, according to Dr. Ljung. The lead author was Dr. Solbritt Rantapåå Dahlqvist, also of Umeå University.

The investigators set out to evaluate serologic risk markers for the development of RA in relation to genetic and environmental risk factors. They compared serologic findings in RA patients, unaffected relatives, and healthy controls.

The researchers found that in 196 individuals with RA and 156 first-degree relatives from 61 multicase families compared with healthy controls, respectively, the median concentrations of the anti-CCP isotypes were 237.0 AU/mL and 2.1 AU/mL vs. 1.5 AU/mL for IgG anti-CCP; 3.4 AU/mL and 1.0 AU/mL vs. 0.6 AU/mL for IgA anti-CCP; and 53 AU/mL and 28.5 AU/mL vs. 18.5 AU/mL for IgM anti-CCP. The median concentrations of rheumatoid factors were 134.5 mcg/mL and 5.2 mcg/mL vs. 3.3 mcg/mL for IgM RF and 8.3 mcg/mL and 1.4 mcg/mL vs. 1.0 mcg/mL for IgA RF.

The investigators also found that RA patients were significantly more often SE (shared-epitope) positive than were unaffected relatives (73.1% vs. 53.6%; P less than .001), but had similar rates of carriage of the PTPN22t variant (47.7% vs. 45.4%).

Both patients and relatives had the variant at higher rates than did controls. Thus, it appears that SE is more important for the development of RA than is the PTPN22t variant, they said.

“The environmental factor of smoking was also more common among the patients and is shown to be an important risk factor” in univariate but not multivariate analysis, they noted.

Indeed, 58% of patients, compared with 46% of relatives, were smokers. Also, IgG and IgA anti-CCP were significantly associated with SE in the patients, but not in the relatives.

Overall, the RA patients had more risk factors for RA than did the relatives (median, four vs. three; P less than .001).

The vast majority of RA patients (93%) had at least three risk factors, whereas only about half (53%) of the relatives had at least three risk factors. Risk factors were defined as anti-CCP antibodies, RF, SE, PTPN22t variant, smoking, and age.

The investigators said they had no relevant financial disclosures.

Both RA patients and their relatives have higher rates of carriage of certain genetic biomarkers than do controls.

Source © Suprijono Suharjoto/Fotolia.com

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 – 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.