Rheumatoid Arthritis

A new questionnaire that takes into consideration both patient and physician perspectives is designed to detect rheumatoid arthritis flares in between appointments, and also may enable patients to self-detect flare and immediately seek an appointment, according to a review of the tool published online Nov. 9 in Annals of the Rheumatic Diseases.

There is a lack of consensus about how to define and measure flare. For some, flares happen in the context of RA worsening over a significant period. This definition of flare does not take into consideration transient exacerbations that spontaneously resolve. Others define flare as any exacerbation, whether transient or long lasting.

At the same time, physicians tend to define flare based on objective signs and clinical features, while patients perceive flare according to symptoms and their effects on daily living.

The Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire melds both patient and physician perspectives, transient and present flares, explained Dr. Jean-Marie Berthelot, of the University of Nantes (France).

The self-administered part of the instrument was based on patient interviews, the findings from which were systematically analyzed to identify attributes patients most commonly used to describe RA flare and the frequency.

In all, 61% of the 99 patients interviewed reported that a flare usually starts with a feeling of swelling in the joints, and 11% mentioned frozen joints. All respondents reported increased pain of varying levels and an increased daily intake of analgesics. Other characteristics included depression (67%), sleep disturbances (77%), and increased fatigue (91%). Also, 96% reported repercussions on daily activities, 88% reported feeling a loss of independence, and 91% reported feeling more fragile emotionally during the flare. Only 9% reported flu-like symptoms.

"From this content analysis, we selected 10 domains to describe RA flare, according to the patient perspective," the researchers explained.

For the physician assessment part of the instrument, 13 rheumatologists participated in a Delphi exercise in which the researchers asked each to list 10 elements that best reflected RA flares. The researchers organized these into domains and eliminated items during a four-round Delphi process in which they selected items only when cited by at least 75% of the participants.

The patients and physicians had four domains in common: joint swelling, pain, sleep disturbance, and intake of analgesics. The common domains were merged, and the remaining domains also were included in the FLARE questionnaire.

However, several issues must be resolved. For example, a threshold of disease worsening is needed to define flare. Also, clarification about the duration of symptom exacerbation is necessary.

The tool needs to be validated in a prospective trial before it can be used to more tightly adjust treatment "based on the overall activity of RA between two visits," the investigators concluded. Once validated "it should be suitable for clinical research and might be for daily clinical practice," they wrote (Ann. Rheum. Dis. 2011 Nov. 9 [doi: 10.1136/ard.2011.150656]).

The study was funded by an unrestricted grant from Sanofi-Aventis France, but the company had no access to the data and was not involved in the study design or data analysis. The authors reported having no conflicts to disclose.

A new questionnaire that takes into consideration both patient and physician perspectives is designed to detect rheumatoid arthritis flares in between appointments, and also may enable patients to self-detect flare and immediately seek an appointment, according to a review of the tool published online Nov. 9 in Annals of the Rheumatic Diseases.

There is a lack of consensus about how to define and measure flare. For some, flares happen in the context of RA worsening over a significant period. This definition of flare does not take into consideration transient exacerbations that spontaneously resolve. Others define flare as any exacerbation, whether transient or long lasting.

At the same time, physicians tend to define flare based on objective signs and clinical features, while patients perceive flare according to symptoms and their effects on daily living.

The Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire melds both patient and physician perspectives, transient and present flares, explained Dr. Jean-Marie Berthelot, of the University of Nantes (France).

The self-administered part of the instrument was based on patient interviews, the findings from which were systematically analyzed to identify attributes patients most commonly used to describe RA flare and the frequency.

In all, 61% of the 99 patients interviewed reported that a flare usually starts with a feeling of swelling in the joints, and 11% mentioned frozen joints. All respondents reported increased pain of varying levels and an increased daily intake of analgesics. Other characteristics included depression (67%), sleep disturbances (77%), and increased fatigue (91%). Also, 96% reported repercussions on daily activities, 88% reported feeling a loss of independence, and 91% reported feeling more fragile emotionally during the flare. Only 9% reported flu-like symptoms.

"From this content analysis, we selected 10 domains to describe RA flare, according to the patient perspective," the researchers explained.

For the physician assessment part of the instrument, 13 rheumatologists participated in a Delphi exercise in which the researchers asked each to list 10 elements that best reflected RA flares. The researchers organized these into domains and eliminated items during a four-round Delphi process in which they selected items only when cited by at least 75% of the participants.

The patients and physicians had four domains in common: joint swelling, pain, sleep disturbance, and intake of analgesics. The common domains were merged, and the remaining domains also were included in the FLARE questionnaire.

However, several issues must be resolved. For example, a threshold of disease worsening is needed to define flare. Also, clarification about the duration of symptom exacerbation is necessary.

The tool needs to be validated in a prospective trial before it can be used to more tightly adjust treatment "based on the overall activity of RA between two visits," the investigators concluded. Once validated "it should be suitable for clinical research and might be for daily clinical practice," they wrote (Ann. Rheum. Dis. 2011 Nov. 9 [doi: 10.1136/ard.2011.150656]).

The study was funded by an unrestricted grant from Sanofi-Aventis France, but the company had no access to the data and was not involved in the study design or data analysis. The authors reported having no conflicts to disclose.

A new questionnaire that takes into consideration both patient and physician perspectives is designed to detect rheumatoid arthritis flares in between appointments, and also may enable patients to self-detect flare and immediately seek an appointment, according to a review of the tool published online Nov. 9 in Annals of the Rheumatic Diseases.

There is a lack of consensus about how to define and measure flare. For some, flares happen in the context of RA worsening over a significant period. This definition of flare does not take into consideration transient exacerbations that spontaneously resolve. Others define flare as any exacerbation, whether transient or long lasting.

At the same time, physicians tend to define flare based on objective signs and clinical features, while patients perceive flare according to symptoms and their effects on daily living.

The Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire melds both patient and physician perspectives, transient and present flares, explained Dr. Jean-Marie Berthelot, of the University of Nantes (France).

The self-administered part of the instrument was based on patient interviews, the findings from which were systematically analyzed to identify attributes patients most commonly used to describe RA flare and the frequency.

In all, 61% of the 99 patients interviewed reported that a flare usually starts with a feeling of swelling in the joints, and 11% mentioned frozen joints. All respondents reported increased pain of varying levels and an increased daily intake of analgesics. Other characteristics included depression (67%), sleep disturbances (77%), and increased fatigue (91%). Also, 96% reported repercussions on daily activities, 88% reported feeling a loss of independence, and 91% reported feeling more fragile emotionally during the flare. Only 9% reported flu-like symptoms.

"From this content analysis, we selected 10 domains to describe RA flare, according to the patient perspective," the researchers explained.

For the physician assessment part of the instrument, 13 rheumatologists participated in a Delphi exercise in which the researchers asked each to list 10 elements that best reflected RA flares. The researchers organized these into domains and eliminated items during a four-round Delphi process in which they selected items only when cited by at least 75% of the participants.

The patients and physicians had four domains in common: joint swelling, pain, sleep disturbance, and intake of analgesics. The common domains were merged, and the remaining domains also were included in the FLARE questionnaire.

However, several issues must be resolved. For example, a threshold of disease worsening is needed to define flare. Also, clarification about the duration of symptom exacerbation is necessary.

The tool needs to be validated in a prospective trial before it can be used to more tightly adjust treatment "based on the overall activity of RA between two visits," the investigators concluded. Once validated "it should be suitable for clinical research and might be for daily clinical practice," they wrote (Ann. Rheum. Dis. 2011 Nov. 9 [doi: 10.1136/ard.2011.150656]).

The study was funded by an unrestricted grant from Sanofi-Aventis France, but the company had no access to the data and was not involved in the study design or data analysis. The authors reported having no conflicts to disclose.

CHICAGO – Adding disease-modifying antirheumatic drugs to anti-TNF therapy failed to enhance drug retention in a study involving 1,630 adults with spondyloarthritis.

Current ankylosing spondylitis recommendations from the Assessment of SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism do not support adding disease-modifying antirheumatic drugs (DMARDs) to anti-TNF therapy, said Dr. Michael Nissen of University Hospital Geneva (Switzerland).

Yet, in practice, cotherapy often is prescribed, and the impact of this addition has not been well studied, he said at the annual meeting of the American College of Rheumatology.

"Utilization of a DMARD with an anti-TNF agent is of no additional benefit in SpA [spondyloarthritis] patients in terms of drug survival," and the study findings support the current treatment recommendations, he added.

Dr. Nissen and his colleagues reviewed data from patient registries that included 1,060 adults with axial spondyloarthritis, 535 with psoriatic arthritis, and 35 with undifferentiated spondyloarthritis.

A total of 1,123 patients (69%) had anti-TNF monotherapy and 507 (31%) had DMARD/anti-TNF cotherapy. Among the cotherapy patients, 72% received methotrexate, 21% received sulfasalazine, and 14% received leflunomide. The mean ages in the monotherapy and cotherapy groups were 43 years and 46 years, respectively, and slightly more than half of patients in each group were male.

After a median follow-up period of 4 years, overall drug retention rates were not significantly different between the monotherapy and cotherapy groups, regardless of the type of anti-TNF treatment. The overall median drug retention was 2.8 years. Significant predictors of drug retention after controlling for confounding variables included male sex, longer disease duration, older age, prior anti-TNF use, steroid use, and baseline scores on the Health Assessment Questionnaire and Bath Ankylosing Spondylitis Disease Activity Index.

In addition, there was no significant effect of DMARDs on anti-TNF retention relating to the type of anti-TNF therapy, clinical manifestations of disease (peripheral vs. axial), or diagnosis (axial spondyloarthritis vs. psoriatic arthritis), Dr. Nissen said.

The study was sponsored by unrestricted research grants from Abbott and Pfizer.

CHICAGO – Adding disease-modifying antirheumatic drugs to anti-TNF therapy failed to enhance drug retention in a study involving 1,630 adults with spondyloarthritis.

Current ankylosing spondylitis recommendations from the Assessment of SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism do not support adding disease-modifying antirheumatic drugs (DMARDs) to anti-TNF therapy, said Dr. Michael Nissen of University Hospital Geneva (Switzerland).

Yet, in practice, cotherapy often is prescribed, and the impact of this addition has not been well studied, he said at the annual meeting of the American College of Rheumatology.

"Utilization of a DMARD with an anti-TNF agent is of no additional benefit in SpA [spondyloarthritis] patients in terms of drug survival," and the study findings support the current treatment recommendations, he added.

Dr. Nissen and his colleagues reviewed data from patient registries that included 1,060 adults with axial spondyloarthritis, 535 with psoriatic arthritis, and 35 with undifferentiated spondyloarthritis.

A total of 1,123 patients (69%) had anti-TNF monotherapy and 507 (31%) had DMARD/anti-TNF cotherapy. Among the cotherapy patients, 72% received methotrexate, 21% received sulfasalazine, and 14% received leflunomide. The mean ages in the monotherapy and cotherapy groups were 43 years and 46 years, respectively, and slightly more than half of patients in each group were male.

After a median follow-up period of 4 years, overall drug retention rates were not significantly different between the monotherapy and cotherapy groups, regardless of the type of anti-TNF treatment. The overall median drug retention was 2.8 years. Significant predictors of drug retention after controlling for confounding variables included male sex, longer disease duration, older age, prior anti-TNF use, steroid use, and baseline scores on the Health Assessment Questionnaire and Bath Ankylosing Spondylitis Disease Activity Index.

In addition, there was no significant effect of DMARDs on anti-TNF retention relating to the type of anti-TNF therapy, clinical manifestations of disease (peripheral vs. axial), or diagnosis (axial spondyloarthritis vs. psoriatic arthritis), Dr. Nissen said.

The study was sponsored by unrestricted research grants from Abbott and Pfizer.

CHICAGO – Adding disease-modifying antirheumatic drugs to anti-TNF therapy failed to enhance drug retention in a study involving 1,630 adults with spondyloarthritis.

Current ankylosing spondylitis recommendations from the Assessment of SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism do not support adding disease-modifying antirheumatic drugs (DMARDs) to anti-TNF therapy, said Dr. Michael Nissen of University Hospital Geneva (Switzerland).

Yet, in practice, cotherapy often is prescribed, and the impact of this addition has not been well studied, he said at the annual meeting of the American College of Rheumatology.

"Utilization of a DMARD with an anti-TNF agent is of no additional benefit in SpA [spondyloarthritis] patients in terms of drug survival," and the study findings support the current treatment recommendations, he added.

Dr. Nissen and his colleagues reviewed data from patient registries that included 1,060 adults with axial spondyloarthritis, 535 with psoriatic arthritis, and 35 with undifferentiated spondyloarthritis.

A total of 1,123 patients (69%) had anti-TNF monotherapy and 507 (31%) had DMARD/anti-TNF cotherapy. Among the cotherapy patients, 72% received methotrexate, 21% received sulfasalazine, and 14% received leflunomide. The mean ages in the monotherapy and cotherapy groups were 43 years and 46 years, respectively, and slightly more than half of patients in each group were male.

After a median follow-up period of 4 years, overall drug retention rates were not significantly different between the monotherapy and cotherapy groups, regardless of the type of anti-TNF treatment. The overall median drug retention was 2.8 years. Significant predictors of drug retention after controlling for confounding variables included male sex, longer disease duration, older age, prior anti-TNF use, steroid use, and baseline scores on the Health Assessment Questionnaire and Bath Ankylosing Spondylitis Disease Activity Index.

In addition, there was no significant effect of DMARDs on anti-TNF retention relating to the type of anti-TNF therapy, clinical manifestations of disease (peripheral vs. axial), or diagnosis (axial spondyloarthritis vs. psoriatic arthritis), Dr. Nissen said.

The study was sponsored by unrestricted research grants from Abbott and Pfizer.

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.

CHICAGO – Early B-cell repopulation and rheumatoid factor positivity predict early relapse in patients with rheumatoid arthritis who are being treated with rituximab, according to an observational study of 104 patients.

"We’re interested in predicting duration of response to rituximab," said lead author Dr. Edward M. Vital of the University of Leeds (England). "[W]hilst the majority of patients do respond, virtually all will relapse at some point. ... [T]he time to relapse is very variable, so that means that we don’t know what the best retreatment regime is. Some advocate retreatment every 6 months, but this may be excessive for some patients, with implications for cost and possibly safety."

With the sensitive B-cell assay, 88% of patients had detectable B cells by 6 months. However, a small group of patients have persistent B-cell depletion at 6 months, and this group had a longer clinical response. In fact, their responses continued to improve from 6 to 9 months, said Dr. Vital. Maintaining a low B-cell number is likely to maintain a good clinical response, he said, although not all patients with B-cell return relapsed immediately. Dr. Vital presented his data at the annual meeting of the American College of Rheumatology.

The study’s objective was to examine whether known predictors of initial response to rituximab could be used after treatment to predict maintenance of response to 12 months.

All 104 patients were positive for either rheumatoid factor or anti–cyclic citrullinated peptide at baseline, prior to treatment with rituximab in a regimen involving infused doses of 1,000 mg with concomitant methotrexate or leflunomide. Of the original study population, 78 (75%) had a known EULAR (European League Against Rheumatism) response at 6 months, and these were investigated for time to relapse. All use of corticosteroids and NSAIDs was similarly controlled in this group, and outcomes were measured by EULAR response and DAS28 (Disease Activity Score including a 28-joint count) at 0, 6, 9, and 12 months by one of two joint-count assessors.

Highly sensitive flow cytometry with a limit of detection of 0.0001 cells x 10⁹/L was used to measure naive, memory B, and plasmablast subsets. Conventional flow cytometry has a limit of detection of 0.01 cells x 10⁹/L.

At 6 months, 44 (57%) of the 78 patients had a EULAR moderate response, and 34 (43%) had a EULAR good response. In patients with detectable B cells at 6 months, DAS28 worsened by a mean 0.45, whereas in patients with undetectable B cells, it improved by a mean 0.44.

At 12 months, 40 patients (51%) had no response, 22 patients (28%) had a EULAR moderate response, and 16 patients (21%) had a EULAR good response.

A binary logistic regression model was created to predict continued EULAR response at 12 months. It included B-cell detection, plasmablast count, rheumatoid factor, and DAS28, and produced a significant (P = .001) model with an overall accuracy of 72%.

"Since rheumatoid factor and DAS28 were the strongest predictors of these, this suggested that it might actually be possible to make a very simple prediction model that doesn’t require specialized techniques," said Dr. Vital.

The authors subsequently created a simplified, two-variable categorical model using a rheumatoid factor threshold of 108 IU/mL, and a DAS28 threshold of 3.7, to predict relapse. This simplified model’s overall accuracy was 69% (P = .001).

"As you can see, we still have a significant model with just a slight reduction in the overall accuracy. ... If at 6 months the DAS28 was less than 3.7 and the rheumatoid factor was less than 108, then 73% of those patients maintained their clinical response out to 12 months ... and if both [DAS28 and rheumatoid factor] were higher, then only 8% of patients responded out to 12 months," said Dr. Vital.

The study concluded that these findings – in particular, the levels used in the two-variable model – need to be validated in another population. When validated, they may allow for selection of retreatment regime based on B-cell biomarkers.

Dr. Vital is on the Roche speakers bureau, and Roche provided rituximab for the patients in this study. The study was funded by the U.K. National Institute for Health Research Doctoral Research Fellowship and sponsored by the NIHR and the University of Leeds.

CHICAGO – Early B-cell repopulation and rheumatoid factor positivity predict early relapse in patients with rheumatoid arthritis who are being treated with rituximab, according to an observational study of 104 patients.

"We’re interested in predicting duration of response to rituximab," said lead author Dr. Edward M. Vital of the University of Leeds (England). "[W]hilst the majority of patients do respond, virtually all will relapse at some point. ... [T]he time to relapse is very variable, so that means that we don’t know what the best retreatment regime is. Some advocate retreatment every 6 months, but this may be excessive for some patients, with implications for cost and possibly safety."

With the sensitive B-cell assay, 88% of patients had detectable B cells by 6 months. However, a small group of patients have persistent B-cell depletion at 6 months, and this group had a longer clinical response. In fact, their responses continued to improve from 6 to 9 months, said Dr. Vital. Maintaining a low B-cell number is likely to maintain a good clinical response, he said, although not all patients with B-cell return relapsed immediately. Dr. Vital presented his data at the annual meeting of the American College of Rheumatology.

The study’s objective was to examine whether known predictors of initial response to rituximab could be used after treatment to predict maintenance of response to 12 months.

All 104 patients were positive for either rheumatoid factor or anti–cyclic citrullinated peptide at baseline, prior to treatment with rituximab in a regimen involving infused doses of 1,000 mg with concomitant methotrexate or leflunomide. Of the original study population, 78 (75%) had a known EULAR (European League Against Rheumatism) response at 6 months, and these were investigated for time to relapse. All use of corticosteroids and NSAIDs was similarly controlled in this group, and outcomes were measured by EULAR response and DAS28 (Disease Activity Score including a 28-joint count) at 0, 6, 9, and 12 months by one of two joint-count assessors.

Highly sensitive flow cytometry with a limit of detection of 0.0001 cells x 10⁹/L was used to measure naive, memory B, and plasmablast subsets. Conventional flow cytometry has a limit of detection of 0.01 cells x 10⁹/L.

At 6 months, 44 (57%) of the 78 patients had a EULAR moderate response, and 34 (43%) had a EULAR good response. In patients with detectable B cells at 6 months, DAS28 worsened by a mean 0.45, whereas in patients with undetectable B cells, it improved by a mean 0.44.

At 12 months, 40 patients (51%) had no response, 22 patients (28%) had a EULAR moderate response, and 16 patients (21%) had a EULAR good response.

A binary logistic regression model was created to predict continued EULAR response at 12 months. It included B-cell detection, plasmablast count, rheumatoid factor, and DAS28, and produced a significant (P = .001) model with an overall accuracy of 72%.

"Since rheumatoid factor and DAS28 were the strongest predictors of these, this suggested that it might actually be possible to make a very simple prediction model that doesn’t require specialized techniques," said Dr. Vital.

The authors subsequently created a simplified, two-variable categorical model using a rheumatoid factor threshold of 108 IU/mL, and a DAS28 threshold of 3.7, to predict relapse. This simplified model’s overall accuracy was 69% (P = .001).

"As you can see, we still have a significant model with just a slight reduction in the overall accuracy. ... If at 6 months the DAS28 was less than 3.7 and the rheumatoid factor was less than 108, then 73% of those patients maintained their clinical response out to 12 months ... and if both [DAS28 and rheumatoid factor] were higher, then only 8% of patients responded out to 12 months," said Dr. Vital.

The study concluded that these findings – in particular, the levels used in the two-variable model – need to be validated in another population. When validated, they may allow for selection of retreatment regime based on B-cell biomarkers.

Dr. Vital is on the Roche speakers bureau, and Roche provided rituximab for the patients in this study. The study was funded by the U.K. National Institute for Health Research Doctoral Research Fellowship and sponsored by the NIHR and the University of Leeds.

CHICAGO – Early B-cell repopulation and rheumatoid factor positivity predict early relapse in patients with rheumatoid arthritis who are being treated with rituximab, according to an observational study of 104 patients.

"We’re interested in predicting duration of response to rituximab," said lead author Dr. Edward M. Vital of the University of Leeds (England). "[W]hilst the majority of patients do respond, virtually all will relapse at some point. ... [T]he time to relapse is very variable, so that means that we don’t know what the best retreatment regime is. Some advocate retreatment every 6 months, but this may be excessive for some patients, with implications for cost and possibly safety."

With the sensitive B-cell assay, 88% of patients had detectable B cells by 6 months. However, a small group of patients have persistent B-cell depletion at 6 months, and this group had a longer clinical response. In fact, their responses continued to improve from 6 to 9 months, said Dr. Vital. Maintaining a low B-cell number is likely to maintain a good clinical response, he said, although not all patients with B-cell return relapsed immediately. Dr. Vital presented his data at the annual meeting of the American College of Rheumatology.

The study’s objective was to examine whether known predictors of initial response to rituximab could be used after treatment to predict maintenance of response to 12 months.

All 104 patients were positive for either rheumatoid factor or anti–cyclic citrullinated peptide at baseline, prior to treatment with rituximab in a regimen involving infused doses of 1,000 mg with concomitant methotrexate or leflunomide. Of the original study population, 78 (75%) had a known EULAR (European League Against Rheumatism) response at 6 months, and these were investigated for time to relapse. All use of corticosteroids and NSAIDs was similarly controlled in this group, and outcomes were measured by EULAR response and DAS28 (Disease Activity Score including a 28-joint count) at 0, 6, 9, and 12 months by one of two joint-count assessors.

Highly sensitive flow cytometry with a limit of detection of 0.0001 cells x 10⁹/L was used to measure naive, memory B, and plasmablast subsets. Conventional flow cytometry has a limit of detection of 0.01 cells x 10⁹/L.

At 6 months, 44 (57%) of the 78 patients had a EULAR moderate response, and 34 (43%) had a EULAR good response. In patients with detectable B cells at 6 months, DAS28 worsened by a mean 0.45, whereas in patients with undetectable B cells, it improved by a mean 0.44.

At 12 months, 40 patients (51%) had no response, 22 patients (28%) had a EULAR moderate response, and 16 patients (21%) had a EULAR good response.

A binary logistic regression model was created to predict continued EULAR response at 12 months. It included B-cell detection, plasmablast count, rheumatoid factor, and DAS28, and produced a significant (P = .001) model with an overall accuracy of 72%.

"Since rheumatoid factor and DAS28 were the strongest predictors of these, this suggested that it might actually be possible to make a very simple prediction model that doesn’t require specialized techniques," said Dr. Vital.

The authors subsequently created a simplified, two-variable categorical model using a rheumatoid factor threshold of 108 IU/mL, and a DAS28 threshold of 3.7, to predict relapse. This simplified model’s overall accuracy was 69% (P = .001).

"As you can see, we still have a significant model with just a slight reduction in the overall accuracy. ... If at 6 months the DAS28 was less than 3.7 and the rheumatoid factor was less than 108, then 73% of those patients maintained their clinical response out to 12 months ... and if both [DAS28 and rheumatoid factor] were higher, then only 8% of patients responded out to 12 months," said Dr. Vital.

The study concluded that these findings – in particular, the levels used in the two-variable model – need to be validated in another population. When validated, they may allow for selection of retreatment regime based on B-cell biomarkers.

Dr. Vital is on the Roche speakers bureau, and Roche provided rituximab for the patients in this study. The study was funded by the U.K. National Institute for Health Research Doctoral Research Fellowship and sponsored by the NIHR and the University of Leeds.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

NEW YORK – Recent data indicate that the subcutaneous formulation of abatacept is comparable in safety to the intravenous formulation in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici, who spoke at "The ‘Tightrope’ of RA Therapy" course sponsored by New York University.

"For the first time, we have a biologic that is available in both infusible and injectable versions, giving patients an option of using one or the other," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics at New York University.

The subcutaneous formulation of abatacept became commercially available in September 2011.

Safety data were presented as part of the phase IIIb, double-blind, 6-month ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) registration trial of subcutaneous abatacept. That study, however, included fewer than 700 patients with rheumatoid arthritis (RA) in both the subcutaneous and intravenous arms (Arthritis Rheum. 2011;63:2854-64). Injection site reactions, including hematoma, pruritus, and erythema, were found in 2.6% of the subcutaneous group and 2.5% of the intravenous group. Serious infections were reported in 0.7% of the subcutaneous group and 1.4% of the intravenous group, said Dr. Yazici, who also is with the Behcet’s Syndrome Evaluation, Treatment, and Research Center at New York University.

A study presented at the 2011 EULAR (European League Against Rheumatism) annual congress by Dr. Rieke Alten, of the University of Medicine in Berlin, provided data on the long-term safety of subcutaneous abatacept. The study included pooled safety data from five clinical trials on 1,879 RA patients who had up to 4.5 years of exposure, representing 3,086 patient-years of use. The subcutaneous formulation was found to produce effects generally consistent with those of the intravenous formulation. Mean duration of exposure was 20 months in the subcutaneous group, compared with 36 months for the intravenous group. Data on the safety of the intravenous formulation came from an integrated safety analysis from the abatacept RA clinical trial program, which included 4,149 patients with 12,132 patient-years of exposure. These data were presented at the 2010 annual meeting of the American College of Rheumatology.

Dr. Alten found the incidence rate for death to be 0.55 events/100 patient-years in the subcutaneous group, compared with 0.60 in the intravenous group. The incidence rate for serious adverse events was 9.53 in the subcutaneous group vs. 14.61 in the intravenous group, and did not increase with increasing abatacept exposure over time. The incidence of injection site reactions in the subcutaneous group was 2.22, and more than 95% of reactions were mild.

As far as serious infections, the incidence rates of the most common ones after subcutaneous injections were 0.36 for pneumonia (vs. 0.46 in the intravenous group), 0.10 for lobar pneumonia (vs. 0.11), 0.10 for herpes zoster (vs. 0.03), and 0.03 (vs. 0.03) for tuberculosis. The incidence rates for malignancies, excluding nonmelanoma skin cancer, were 0.68 in patients receiving subcutaneous abatacept and 0.73 in the intravenous group. The incidence rates for autoimmune events, including psoriasis and Sjögren’s syndrome, were 1.28 with subcutaneous administration and 1.99 with intravenous use.

Unlike the intravenous formulation, subcutaneous abatacept can be self-administered, allowing patients to forego trips to the physician’s office for infusions – a benefit for those who have busy schedules or transportation limitations. Diabetics may prefer the subcutaneous formulation because it does not contain maltose, which can interfere with the accuracy of blood sugar readings. On the other hand, some patients may be anxious about self-injection or unwilling to take the time to secure their own supplies (such as bandages, alcohol swabs, cotton balls, and puncture-resistant containers for syringes) or prepare the syringes, which must be kept cool before use and then warmed before injection; they may prefer the monthly infusions given at the doctor’s office.

The label’s product information for abatacept recommends a single intravenous infusion as a loading dose (based on body weight) preceding the first 125-mg subcutaneous injection. Dr. Yazici reviewed recent data that challenged that recommendation. These findings come from a study by Dr. Peter T. Nash of the University of Queensland, Brisbane, that were presented at the 2011 EULAR congress. The study involved a comparison of open-label data from two phase III trials that showed comparable improvements with subcutaneous abatacept, with or without an intravenous loading dose, on physical function, as assessed by the Health Assessment Questionnaire–Disease Index, and disease activity, as assessed by the Disease Activity Score 28/C-reactive protein.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Alten receives grant or research support from, is a consultant for, or is on the speakers bureau of Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Norvartis Pharmaceuticals, Roche, and Wyeth Pharmaceuticals.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.

"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.

There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.

Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.

There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.

The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.

Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).

The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.

Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.

The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.

In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.

Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.

Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.

*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

NEW YORK – The low levels of immunoglobulin G seen in a group of patients receiving rituximab for rheumatoid arthritis were associated with a twofold increased risk of serious infections, judging from the results of a 5-year prospective French register of 2,000 patients, according to Dr. Yusuf Yazici.

“These results give us one piece of evidence to support what investigators have long suspected: Low IgG levels may increase risk of infections,” said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the New York University Hospital for Joint Diseases.*

Of the risk factors investigated by Dr. Jacques-Eric Gottenberg of the Strasbourg (France) University Hospital and his associates, only low serum IgG levels – not gamma globulin or immunoglobulin M (IgM) levels – were associated with serious infections in rheumatoid arthritis (RA) patients treated with rituximab, according to Dr. Yazici. This finding suggests that serum IgG levels in particular should be checked before each new cycle of rituximab and that the risk/benefit ratio of rituximab should be carefully assessed for those with low IgG levels. A therapy other than rituximab should be considered for patients with low immunoglobulin G (IgG) levels who already have a severe infection or severe comorbidities, according to Dr. Gottenberg’s findings.

The French AIR (Autoimmunity and Rituximab) Registry is a 5-year, prospective, multicenter study begun in 2006 that prospectively collects data on patients treated with rituximab on and off label for refractory arthritides. It is thought to be the largest prospective study, based on a national registry, focusing on severe infections in RA patients treated with rituximab in a clinical setting. Many patients have comorbidities, such as cancer, chronic lung disease, cardiac insufficiency, or diabetes. A nationwide initiative, most patients were registered from rheumatology departments while less than 10% originated from internal medicine departments. The 88 centers who participated in the register write more than 85% of all rituximab prescriptions in France for nonhematologic, nononcologic indications.

"You can’t suppress IgG levels forever without expecting some increase in infections."

Since this was a noninterventional study, no laboratory exams were required either at baseline or after rituximab treatment. Even though immunoglobulin levels are not routinely assessed during rituximab therapy, of the 2000 patients with RA included in the AIR Registry, gamma globulin, IgM, or IgG levels after rituximab treatment had been collected in almost 60% of enrolled patients. Of those who had undergone these analyses, 15.5% had low levels of serum gamma globulin less than 6 g/L), 26.6% had low levels of IgM less than 0.5 g/L) and 12.1% had low IgG levels (less than 6 g/L).

The authors looked at the rates of serious infections (defined as an infection occurring during the 12 months following each infusion of rituximab that required hospitalization and/or intravenous antibiotics and/or resulted in death) in patients with normal and low levels of gamma globulin, IgM, or IgG. Univariate analysis adjusted according to follow-up duration revealed that only low IgG levels after rituximab were associated with a significantly increased risk of serious infections, with almost a twofold increase in risk (odds ratio, 1.99; 95% confidence interval, 1.2-3.3; P = .008). No significant effects were found for low levels of gamma globulin (OR, 1.5; 95% CI, 0.9-2.5; P = .09) or IgM (OR, 1.5; 95% CI, 0.9-2.3; P = .08).

In a multivariate analysis, when the researchers adjusted for older age, previous cancer, or serious or recurrent infections, only low IgG after rituximab remained associated with serious infections. In published work, Dr. Gottenberg reported that chronic lung disease and/or cardiac insufficiency and extraarticular involvement also rendered RA patients treated with rituximab more prone to severe infections (Arthritis Rheum. 2010;62[9]:2625-32).

For all measures serious infections were more frequent in those with lower levels of immunologic indices. For instance, 13.5% of patients with low gamma globulin levels after rituximab had serious infections, compared with 8.8% of those with normal gamma globulin levels. Rates of serious infection, as indicated by the ratio of low to normal levels for IgM, were 11.8%:8.1% while the rates for IgG were 15.1%:8.2%.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech. Dr. Gottenberg reported a relevant financial relationship with Roche.

* Clarification: This story was updated on 12/12/2011.

CHICAGO – Combination induction therapy with adalimumab and methotrexate was superior to methotrexate alone for the treatment of patients with early rheumatoid arthritis in the randomized, controlled, multicenter HIT HARD trial.

The mean 28-joint count disease activity score (DAS28) was reduced from 6.2 to 3.0 after a 24-week induction phase in 87 RA patients randomized to receive combination therapy, which was significantly greater than the reduction from 6.3 to 3.5 in 85 patients randomized to receive methotrexate monotherapy for 24 weeks, according to Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

After 24 weeks, adalimumab was withdrawn in the patients on combination therapy, and both groups received only methotrexate for an additional 24 weeks. The 48-week DAS28 – the primary end point of the double-blind study – remained numerically, but not significantly, lower in the group who initially received combination therapy, compared with the group who received initial monotherapy (3.2 vs. 3.4, respectively), said Dr. Burmester, professor of rheumatology at the Charité-Universitatsmedizin Berlin.

As with the primary outcome measure, the differences between the combination therapy and methotrexate monotherapy groups on secondary outcome measures, including remission (defined as DAS28 less than 2.6), ACR50 and ACR70 response rates (indicating 50% and 70% improvement in the signs and symptoms of disease), and functional status as measured by the Health Assessment Questionnaire (HAQ) differed significantly at week 24, but not at week 48.

For example, 47% vs. 31% of patients in the combination and monotherapy groups, respectively, achieved remission by week 24, but those percentages changed to 44% and 37% by week 48. Also, HAQ scores, which were 1.4 and 1.3 at baseline, were 0.49 vs. 0.72 at 24 weeks, compared with 0.60 and 0.65 at 48 weeks.

However, despite the lack of a significant difference in the DAS28 scores and the secondary outcome measures between the two groups at 48-week follow-up, there was a significant difference in regard to radiographic progression of disease: mean total van der Heijde/Sharp scores at that time were 6.3 and 11.4 in the groups, respectively, Dr. Burmester said. The extent to which this difference is clinically meaningful remains unclear, he noted.

Patients in the study had early RA with duration of no more than 1 year (with 87% having disease duration of 3 months or less) and had not been treated previously with disease-modifying antirheumatic drugs. All had active disease, swollen and tender joint counts of at least six, and C-reactive protein levels of at least 10 mg/L. Those in the combination therapy group received 15 mg/week of subcutaneous methotrexate plus 40 mg of adalimumab every other week; monotherapy patients received 15 mg/week of methotrexate plus placebo, and no new safety signals were detected during the course of the study.

The findings suggest that combination therapy with adalimumab and methotrexate is significantly superior to methotrexate alone for induction therapy in early RA. Combination therapy produces sustained benefits in regard to radiographic progression at 48 weeks, even when adalimumab is withdrawn at 24 weeks.

"The numerical increase in the clinical outcome parameters of the group on combination therapy, which became apparent at around 40 weeks following treatment initiation, may reflect the loss of response after removal of adalimumab and is a finding that requires additional study, Dr. Burmester noted.

In an unrelated study also presented at ACR 2011, Dr. Arthur F. Kavanaugh, professor of medicine, and director of the center for innovative therapy in the division of rheumatology, allergy, and immunology at the University of California at San Diego and his colleagues similarly found that patients on combination adalimumab and methotrexate who achieved stable low-disease activity were able to maintain that response following adalimumab withdrawal in the OPTIMA (Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early RA) Trial. But they also found that those patients with a low HAQ score at baseline were more likely than were other patients to fare well after adalimumab withdrawal, a finding that suggests that those with higher scores might do better if combination therapy is continued.

Still, this question remains, according to Dr. Burmester: "Is it medically or economically justifiable to use this [combination] induction therapy, which rapidly leads to improvement, or should we just wait for the success of methotrexate later?"

Another question that warrants study is whether higher doses of methotrexate would be better, he said, adding, "But there is one very important message: Treat as early as possible."

This study was funded by the German Ministry of Science. Dr. Burmester disclosed financial and other relationships with Abbott, MSD, Pfizer, and UCB. Other study authors also disclosed relationships with these companies and several others, including Bristol-Myers Squibb, Horizon Pharma, Merck Pharma, Merck Serono, Nitec Pharma, Novartis, Roche, and Wyeth Pharmaceuticals.

CHICAGO – Combination induction therapy with adalimumab and methotrexate was superior to methotrexate alone for the treatment of patients with early rheumatoid arthritis in the randomized, controlled, multicenter HIT HARD trial.

The mean 28-joint count disease activity score (DAS28) was reduced from 6.2 to 3.0 after a 24-week induction phase in 87 RA patients randomized to receive combination therapy, which was significantly greater than the reduction from 6.3 to 3.5 in 85 patients randomized to receive methotrexate monotherapy for 24 weeks, according to Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

After 24 weeks, adalimumab was withdrawn in the patients on combination therapy, and both groups received only methotrexate for an additional 24 weeks. The 48-week DAS28 – the primary end point of the double-blind study – remained numerically, but not significantly, lower in the group who initially received combination therapy, compared with the group who received initial monotherapy (3.2 vs. 3.4, respectively), said Dr. Burmester, professor of rheumatology at the Charité-Universitatsmedizin Berlin.

As with the primary outcome measure, the differences between the combination therapy and methotrexate monotherapy groups on secondary outcome measures, including remission (defined as DAS28 less than 2.6), ACR50 and ACR70 response rates (indicating 50% and 70% improvement in the signs and symptoms of disease), and functional status as measured by the Health Assessment Questionnaire (HAQ) differed significantly at week 24, but not at week 48.

For example, 47% vs. 31% of patients in the combination and monotherapy groups, respectively, achieved remission by week 24, but those percentages changed to 44% and 37% by week 48. Also, HAQ scores, which were 1.4 and 1.3 at baseline, were 0.49 vs. 0.72 at 24 weeks, compared with 0.60 and 0.65 at 48 weeks.

However, despite the lack of a significant difference in the DAS28 scores and the secondary outcome measures between the two groups at 48-week follow-up, there was a significant difference in regard to radiographic progression of disease: mean total van der Heijde/Sharp scores at that time were 6.3 and 11.4 in the groups, respectively, Dr. Burmester said. The extent to which this difference is clinically meaningful remains unclear, he noted.

Patients in the study had early RA with duration of no more than 1 year (with 87% having disease duration of 3 months or less) and had not been treated previously with disease-modifying antirheumatic drugs. All had active disease, swollen and tender joint counts of at least six, and C-reactive protein levels of at least 10 mg/L. Those in the combination therapy group received 15 mg/week of subcutaneous methotrexate plus 40 mg of adalimumab every other week; monotherapy patients received 15 mg/week of methotrexate plus placebo, and no new safety signals were detected during the course of the study.

The findings suggest that combination therapy with adalimumab and methotrexate is significantly superior to methotrexate alone for induction therapy in early RA. Combination therapy produces sustained benefits in regard to radiographic progression at 48 weeks, even when adalimumab is withdrawn at 24 weeks.

"The numerical increase in the clinical outcome parameters of the group on combination therapy, which became apparent at around 40 weeks following treatment initiation, may reflect the loss of response after removal of adalimumab and is a finding that requires additional study, Dr. Burmester noted.

In an unrelated study also presented at ACR 2011, Dr. Arthur F. Kavanaugh, professor of medicine, and director of the center for innovative therapy in the division of rheumatology, allergy, and immunology at the University of California at San Diego and his colleagues similarly found that patients on combination adalimumab and methotrexate who achieved stable low-disease activity were able to maintain that response following adalimumab withdrawal in the OPTIMA (Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early RA) Trial. But they also found that those patients with a low HAQ score at baseline were more likely than were other patients to fare well after adalimumab withdrawal, a finding that suggests that those with higher scores might do better if combination therapy is continued.

Still, this question remains, according to Dr. Burmester: "Is it medically or economically justifiable to use this [combination] induction therapy, which rapidly leads to improvement, or should we just wait for the success of methotrexate later?"

Another question that warrants study is whether higher doses of methotrexate would be better, he said, adding, "But there is one very important message: Treat as early as possible."

This study was funded by the German Ministry of Science. Dr. Burmester disclosed financial and other relationships with Abbott, MSD, Pfizer, and UCB. Other study authors also disclosed relationships with these companies and several others, including Bristol-Myers Squibb, Horizon Pharma, Merck Pharma, Merck Serono, Nitec Pharma, Novartis, Roche, and Wyeth Pharmaceuticals.

CHICAGO – Combination induction therapy with adalimumab and methotrexate was superior to methotrexate alone for the treatment of patients with early rheumatoid arthritis in the randomized, controlled, multicenter HIT HARD trial.

The mean 28-joint count disease activity score (DAS28) was reduced from 6.2 to 3.0 after a 24-week induction phase in 87 RA patients randomized to receive combination therapy, which was significantly greater than the reduction from 6.3 to 3.5 in 85 patients randomized to receive methotrexate monotherapy for 24 weeks, according to Dr. Gerd R. Burmester reported at the annual meeting of the American College of Rheumatology.

After 24 weeks, adalimumab was withdrawn in the patients on combination therapy, and both groups received only methotrexate for an additional 24 weeks. The 48-week DAS28 – the primary end point of the double-blind study – remained numerically, but not significantly, lower in the group who initially received combination therapy, compared with the group who received initial monotherapy (3.2 vs. 3.4, respectively), said Dr. Burmester, professor of rheumatology at the Charité-Universitatsmedizin Berlin.

As with the primary outcome measure, the differences between the combination therapy and methotrexate monotherapy groups on secondary outcome measures, including remission (defined as DAS28 less than 2.6), ACR50 and ACR70 response rates (indicating 50% and 70% improvement in the signs and symptoms of disease), and functional status as measured by the Health Assessment Questionnaire (HAQ) differed significantly at week 24, but not at week 48.

For example, 47% vs. 31% of patients in the combination and monotherapy groups, respectively, achieved remission by week 24, but those percentages changed to 44% and 37% by week 48. Also, HAQ scores, which were 1.4 and 1.3 at baseline, were 0.49 vs. 0.72 at 24 weeks, compared with 0.60 and 0.65 at 48 weeks.

However, despite the lack of a significant difference in the DAS28 scores and the secondary outcome measures between the two groups at 48-week follow-up, there was a significant difference in regard to radiographic progression of disease: mean total van der Heijde/Sharp scores at that time were 6.3 and 11.4 in the groups, respectively, Dr. Burmester said. The extent to which this difference is clinically meaningful remains unclear, he noted.

Patients in the study had early RA with duration of no more than 1 year (with 87% having disease duration of 3 months or less) and had not been treated previously with disease-modifying antirheumatic drugs. All had active disease, swollen and tender joint counts of at least six, and C-reactive protein levels of at least 10 mg/L. Those in the combination therapy group received 15 mg/week of subcutaneous methotrexate plus 40 mg of adalimumab every other week; monotherapy patients received 15 mg/week of methotrexate plus placebo, and no new safety signals were detected during the course of the study.

The findings suggest that combination therapy with adalimumab and methotrexate is significantly superior to methotrexate alone for induction therapy in early RA. Combination therapy produces sustained benefits in regard to radiographic progression at 48 weeks, even when adalimumab is withdrawn at 24 weeks.

"The numerical increase in the clinical outcome parameters of the group on combination therapy, which became apparent at around 40 weeks following treatment initiation, may reflect the loss of response after removal of adalimumab and is a finding that requires additional study, Dr. Burmester noted.

In an unrelated study also presented at ACR 2011, Dr. Arthur F. Kavanaugh, professor of medicine, and director of the center for innovative therapy in the division of rheumatology, allergy, and immunology at the University of California at San Diego and his colleagues similarly found that patients on combination adalimumab and methotrexate who achieved stable low-disease activity were able to maintain that response following adalimumab withdrawal in the OPTIMA (Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early RA) Trial. But they also found that those patients with a low HAQ score at baseline were more likely than were other patients to fare well after adalimumab withdrawal, a finding that suggests that those with higher scores might do better if combination therapy is continued.

Still, this question remains, according to Dr. Burmester: "Is it medically or economically justifiable to use this [combination] induction therapy, which rapidly leads to improvement, or should we just wait for the success of methotrexate later?"

Another question that warrants study is whether higher doses of methotrexate would be better, he said, adding, "But there is one very important message: Treat as early as possible."

This study was funded by the German Ministry of Science. Dr. Burmester disclosed financial and other relationships with Abbott, MSD, Pfizer, and UCB. Other study authors also disclosed relationships with these companies and several others, including Bristol-Myers Squibb, Horizon Pharma, Merck Pharma, Merck Serono, Nitec Pharma, Novartis, Roche, and Wyeth Pharmaceuticals.

Dr. Martin Lee maintains his come-what-may intention to kayak the circumference of Great Britain, despite a growing number of challenges to his plan to raise £100,000 in pledges for the National Rheumatoid Arthritis Society.

His launch date is April 1, 2012. Dr. Lee intends to put his kayak into the Thames at the Ahoy Centre in Greenwich. "There is absolutely no chance that I won’t launch, come wind, rain, or high water!" he declared in a recent interview.

Photos courtesy Dr. Martin Lee

When setting his fund-raising goal, Dr. Lee did not take into account new regulations that limit contributions by pharmaceutical companies to charitable efforts such as his.

Dr. Lee’s undertaking is inspired by his beloved aunt, Maureen Rayner, of Bournemouth in the south of England, who has active rheumatoid arthritis despite treatment with various anti-tumor necrosis factor drugs as well as rituximab. "She is severely limited in activities or daily living by her RA but is incredibly stoical and non-complaining," noted Dr. Lee.

The 32-year-old, newly minted rheumatologist estimates that it will take him 100 days to kayak the 2,600 miles.

Training must be worked in around a tight schedule of a full-time position at the Royal National Hospital of Rheumatic Diseases in Bath that involves 2-3 hours of daily commuting. By the time he gets to the gym to work out, the day has darkened and he is tired. Yet Dr. Lee does not flag. "I have been training about 2 hours a day in the gym and have been doing lots of running. As the days have been getting shorter, it has been more and more difficult getting on the water," he said.

Running has included about 10 half marathons in the last 3 months. However, an injury in the form of piriformis syndrome has hampered his training.

Food is another important part of Dr. Lee’s training regimen. "I have been trying to lose weight (unsuccessfully) to improve my half marathon times but am now looking to maintain fat stores as I will need a higher body fat percentage for the challenge to cope with the 8-9 hours of paddling a day," he said.

Leaner than his body mass index are his pledge totals. To date, Dr. Lee has raised £2,500 in pledges. "New regulations regarding donations from pharmaceutical companies have severely hampered my fundraising. If I complete the challenge but have not raised the £100,000 I will feel that I have failed as the fundraising is my main target and kayaking around the United Kingdom as a means to achieve that target," noted Dr. Lee

"I don’t know whether the same [Association of the British Pharmaceutical Industry] rules apply to U.S. pharmaceutical companies as they do in the United Kingdom, but I suspect the rules are even stricter in the United States, if anything." This leaves much of the charitable donations in the hands of individuals.

Once Dr. Lee is in the water and underway, "I will be using a spot tracker device so people can visit the website and keep track of where I am. I hope to post a blog most days (which may be via friends/family). I hope to post photos fairly regularly depending on when I can get Internet access."

For more information about the challenge and to sponsor Dr. Lee, visit www.martinkayaking.co.uk.

Dr. Martin Lee maintains his come-what-may intention to kayak the circumference of Great Britain, despite a growing number of challenges to his plan to raise £100,000 in pledges for the National Rheumatoid Arthritis Society.

His launch date is April 1, 2012. Dr. Lee intends to put his kayak into the Thames at the Ahoy Centre in Greenwich. "There is absolutely no chance that I won’t launch, come wind, rain, or high water!" he declared in a recent interview.

Photos courtesy Dr. Martin Lee

When setting his fund-raising goal, Dr. Lee did not take into account new regulations that limit contributions by pharmaceutical companies to charitable efforts such as his.

Dr. Lee’s undertaking is inspired by his beloved aunt, Maureen Rayner, of Bournemouth in the south of England, who has active rheumatoid arthritis despite treatment with various anti-tumor necrosis factor drugs as well as rituximab. "She is severely limited in activities or daily living by her RA but is incredibly stoical and non-complaining," noted Dr. Lee.

The 32-year-old, newly minted rheumatologist estimates that it will take him 100 days to kayak the 2,600 miles.

Training must be worked in around a tight schedule of a full-time position at the Royal National Hospital of Rheumatic Diseases in Bath that involves 2-3 hours of daily commuting. By the time he gets to the gym to work out, the day has darkened and he is tired. Yet Dr. Lee does not flag. "I have been training about 2 hours a day in the gym and have been doing lots of running. As the days have been getting shorter, it has been more and more difficult getting on the water," he said.

Running has included about 10 half marathons in the last 3 months. However, an injury in the form of piriformis syndrome has hampered his training.

Food is another important part of Dr. Lee’s training regimen. "I have been trying to lose weight (unsuccessfully) to improve my half marathon times but am now looking to maintain fat stores as I will need a higher body fat percentage for the challenge to cope with the 8-9 hours of paddling a day," he said.

Leaner than his body mass index are his pledge totals. To date, Dr. Lee has raised £2,500 in pledges. "New regulations regarding donations from pharmaceutical companies have severely hampered my fundraising. If I complete the challenge but have not raised the £100,000 I will feel that I have failed as the fundraising is my main target and kayaking around the United Kingdom as a means to achieve that target," noted Dr. Lee

"I don’t know whether the same [Association of the British Pharmaceutical Industry] rules apply to U.S. pharmaceutical companies as they do in the United Kingdom, but I suspect the rules are even stricter in the United States, if anything." This leaves much of the charitable donations in the hands of individuals.

Once Dr. Lee is in the water and underway, "I will be using a spot tracker device so people can visit the website and keep track of where I am. I hope to post a blog most days (which may be via friends/family). I hope to post photos fairly regularly depending on when I can get Internet access."

For more information about the challenge and to sponsor Dr. Lee, visit www.martinkayaking.co.uk.

Dr. Martin Lee maintains his come-what-may intention to kayak the circumference of Great Britain, despite a growing number of challenges to his plan to raise £100,000 in pledges for the National Rheumatoid Arthritis Society.

His launch date is April 1, 2012. Dr. Lee intends to put his kayak into the Thames at the Ahoy Centre in Greenwich. "There is absolutely no chance that I won’t launch, come wind, rain, or high water!" he declared in a recent interview.

Photos courtesy Dr. Martin Lee

When setting his fund-raising goal, Dr. Lee did not take into account new regulations that limit contributions by pharmaceutical companies to charitable efforts such as his.

Dr. Lee’s undertaking is inspired by his beloved aunt, Maureen Rayner, of Bournemouth in the south of England, who has active rheumatoid arthritis despite treatment with various anti-tumor necrosis factor drugs as well as rituximab. "She is severely limited in activities or daily living by her RA but is incredibly stoical and non-complaining," noted Dr. Lee.

The 32-year-old, newly minted rheumatologist estimates that it will take him 100 days to kayak the 2,600 miles.

Training must be worked in around a tight schedule of a full-time position at the Royal National Hospital of Rheumatic Diseases in Bath that involves 2-3 hours of daily commuting. By the time he gets to the gym to work out, the day has darkened and he is tired. Yet Dr. Lee does not flag. "I have been training about 2 hours a day in the gym and have been doing lots of running. As the days have been getting shorter, it has been more and more difficult getting on the water," he said.

Running has included about 10 half marathons in the last 3 months. However, an injury in the form of piriformis syndrome has hampered his training.

Food is another important part of Dr. Lee’s training regimen. "I have been trying to lose weight (unsuccessfully) to improve my half marathon times but am now looking to maintain fat stores as I will need a higher body fat percentage for the challenge to cope with the 8-9 hours of paddling a day," he said.

Leaner than his body mass index are his pledge totals. To date, Dr. Lee has raised £2,500 in pledges. "New regulations regarding donations from pharmaceutical companies have severely hampered my fundraising. If I complete the challenge but have not raised the £100,000 I will feel that I have failed as the fundraising is my main target and kayaking around the United Kingdom as a means to achieve that target," noted Dr. Lee

"I don’t know whether the same [Association of the British Pharmaceutical Industry] rules apply to U.S. pharmaceutical companies as they do in the United Kingdom, but I suspect the rules are even stricter in the United States, if anything." This leaves much of the charitable donations in the hands of individuals.

Once Dr. Lee is in the water and underway, "I will be using a spot tracker device so people can visit the website and keep track of where I am. I hope to post a blog most days (which may be via friends/family). I hope to post photos fairly regularly depending on when I can get Internet access."

For more information about the challenge and to sponsor Dr. Lee, visit www.martinkayaking.co.uk.