BSR Annual Conference 2012

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

GLASGOW, SCOTLAND – Five-year mortality following the diagnosis of systemic rheumatoid vasculitis hovers around 60%, according to an analysis of 34 cases identified in a British-based patient registry.

Although the annual incidence of SRV has reportedly been decreasing since the 1990s, these data suggest it remains a problem despite the introduction of modern immunosuppressive therapies and the use of earlier and more aggressive treatment for rheumatoid arthritis, Dr. Eleana Ntatsaki, a rheumatology specialist trainee at Norfolk and Norwich (England) University Hospital, said at the annual meeting of the British Society for Rheumatology.

The Norfolk Vasculitis Register (NORVASC) is a prospective patient registry established in 1988 to log cases of vasculitis that occur in the county of Norfolk, England. This is a region particularly well suited to epidemiological study, as it is an isolated geographical area with a stable and well-defined population. This is also one of the reasons the Norfolk Arthritis Register (NOAR) is situated in this part of the country.

Between Jan. 1, 2001, and Dec. 31, 2010, a total of 34 cases were reviewed in detail, with 18 patients (10 men) confirmed as having SRV according to previously published criteria (Am. J. Med. 1984;76:377-84), chart review, and independent physician assessment.

The median age of confirmed cases at diagnosis was 72 years and the average disease duration before SRV diagnosis was nearly 16 years. All patients were rheumatoid factor positive, 13 had documented erosive disease, and three had rheumatoid nodules.

All patients had been treated with steroids, a median of two prior DMARDs had been used (methotrexate in 65% of patients), and two patients had received biologic agents. SRV had been treated with intravenous cyclophosphamide (median six cycles) in all but one patient.

The average annual incidence of SRV was calculated to be 3.9 per million (95% confidence interval [CI], 2.3-6.2). This was substantially lower than the 9.1 per million (95% CI, 6.8-12.0) seen in a reference population of 47 patients who developed the complication between 1998 and 2000.

The average annual incidence rates in 2001-2010 were 4.5 (95% CI, 2.2-8.3) for men and 3.4 (95% CI, 1.4-6.6) for women. In 1998-2000, the rates were 8.9 (95% CI, 5.7-13.1) for men and 8.7 (95% CI, 5.6-12.8) for women.

No statistically significant differences were found in the number of patients experiencing systemic, cutaneous, neurologic, pulmonary, renal, ophthalmic, or gastrointestinal manifestations between the two time periods.

Mortality rates at 1 year were also similar between the cohorts, at 12% for 2001-2010 and 14% for 1998-2000. Five-year mortality rates were 60% and 51%, respectively.

"Modern immunosuppression therapy seems to be associated with a decrease in the incidence" of systemic rheumatoid vasculitis, said Dr. Ntatsaki, "but has had no significant influence on clinical features, or outcome."

Whether the decrease in incidence can truly be attributed to methotrexate or improvements in RA treatment in general is questionable, suggested Dr. Deborah Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

This decline in the incidence of rheumatoid vasculitis is not necessarily because rheumatoid arthritis treatments have improved, she said. "Perhaps it is just the natural history of rheumatoid arthritis that vasculitis is becoming rare. Clearly when people do get it they do just as badly as they ever did, and perhaps all this about methotrexate is completely coincidental."

Dr. Ntatsaki reported having no financial disclosures.

GLASGOW, SCOTLAND – Five-year mortality following the diagnosis of systemic rheumatoid vasculitis hovers around 60%, according to an analysis of 34 cases identified in a British-based patient registry.

Although the annual incidence of SRV has reportedly been decreasing since the 1990s, these data suggest it remains a problem despite the introduction of modern immunosuppressive therapies and the use of earlier and more aggressive treatment for rheumatoid arthritis, Dr. Eleana Ntatsaki, a rheumatology specialist trainee at Norfolk and Norwich (England) University Hospital, said at the annual meeting of the British Society for Rheumatology.

The Norfolk Vasculitis Register (NORVASC) is a prospective patient registry established in 1988 to log cases of vasculitis that occur in the county of Norfolk, England. This is a region particularly well suited to epidemiological study, as it is an isolated geographical area with a stable and well-defined population. This is also one of the reasons the Norfolk Arthritis Register (NOAR) is situated in this part of the country.

Between Jan. 1, 2001, and Dec. 31, 2010, a total of 34 cases were reviewed in detail, with 18 patients (10 men) confirmed as having SRV according to previously published criteria (Am. J. Med. 1984;76:377-84), chart review, and independent physician assessment.

The median age of confirmed cases at diagnosis was 72 years and the average disease duration before SRV diagnosis was nearly 16 years. All patients were rheumatoid factor positive, 13 had documented erosive disease, and three had rheumatoid nodules.

All patients had been treated with steroids, a median of two prior DMARDs had been used (methotrexate in 65% of patients), and two patients had received biologic agents. SRV had been treated with intravenous cyclophosphamide (median six cycles) in all but one patient.

The average annual incidence of SRV was calculated to be 3.9 per million (95% confidence interval [CI], 2.3-6.2). This was substantially lower than the 9.1 per million (95% CI, 6.8-12.0) seen in a reference population of 47 patients who developed the complication between 1998 and 2000.

The average annual incidence rates in 2001-2010 were 4.5 (95% CI, 2.2-8.3) for men and 3.4 (95% CI, 1.4-6.6) for women. In 1998-2000, the rates were 8.9 (95% CI, 5.7-13.1) for men and 8.7 (95% CI, 5.6-12.8) for women.

No statistically significant differences were found in the number of patients experiencing systemic, cutaneous, neurologic, pulmonary, renal, ophthalmic, or gastrointestinal manifestations between the two time periods.

Mortality rates at 1 year were also similar between the cohorts, at 12% for 2001-2010 and 14% for 1998-2000. Five-year mortality rates were 60% and 51%, respectively.

"Modern immunosuppression therapy seems to be associated with a decrease in the incidence" of systemic rheumatoid vasculitis, said Dr. Ntatsaki, "but has had no significant influence on clinical features, or outcome."

Whether the decrease in incidence can truly be attributed to methotrexate or improvements in RA treatment in general is questionable, suggested Dr. Deborah Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

This decline in the incidence of rheumatoid vasculitis is not necessarily because rheumatoid arthritis treatments have improved, she said. "Perhaps it is just the natural history of rheumatoid arthritis that vasculitis is becoming rare. Clearly when people do get it they do just as badly as they ever did, and perhaps all this about methotrexate is completely coincidental."

Dr. Ntatsaki reported having no financial disclosures.

GLASGOW, SCOTLAND – Five-year mortality following the diagnosis of systemic rheumatoid vasculitis hovers around 60%, according to an analysis of 34 cases identified in a British-based patient registry.

Although the annual incidence of SRV has reportedly been decreasing since the 1990s, these data suggest it remains a problem despite the introduction of modern immunosuppressive therapies and the use of earlier and more aggressive treatment for rheumatoid arthritis, Dr. Eleana Ntatsaki, a rheumatology specialist trainee at Norfolk and Norwich (England) University Hospital, said at the annual meeting of the British Society for Rheumatology.

The Norfolk Vasculitis Register (NORVASC) is a prospective patient registry established in 1988 to log cases of vasculitis that occur in the county of Norfolk, England. This is a region particularly well suited to epidemiological study, as it is an isolated geographical area with a stable and well-defined population. This is also one of the reasons the Norfolk Arthritis Register (NOAR) is situated in this part of the country.

Between Jan. 1, 2001, and Dec. 31, 2010, a total of 34 cases were reviewed in detail, with 18 patients (10 men) confirmed as having SRV according to previously published criteria (Am. J. Med. 1984;76:377-84), chart review, and independent physician assessment.

The median age of confirmed cases at diagnosis was 72 years and the average disease duration before SRV diagnosis was nearly 16 years. All patients were rheumatoid factor positive, 13 had documented erosive disease, and three had rheumatoid nodules.

All patients had been treated with steroids, a median of two prior DMARDs had been used (methotrexate in 65% of patients), and two patients had received biologic agents. SRV had been treated with intravenous cyclophosphamide (median six cycles) in all but one patient.

The average annual incidence of SRV was calculated to be 3.9 per million (95% confidence interval [CI], 2.3-6.2). This was substantially lower than the 9.1 per million (95% CI, 6.8-12.0) seen in a reference population of 47 patients who developed the complication between 1998 and 2000.

The average annual incidence rates in 2001-2010 were 4.5 (95% CI, 2.2-8.3) for men and 3.4 (95% CI, 1.4-6.6) for women. In 1998-2000, the rates were 8.9 (95% CI, 5.7-13.1) for men and 8.7 (95% CI, 5.6-12.8) for women.

No statistically significant differences were found in the number of patients experiencing systemic, cutaneous, neurologic, pulmonary, renal, ophthalmic, or gastrointestinal manifestations between the two time periods.

Mortality rates at 1 year were also similar between the cohorts, at 12% for 2001-2010 and 14% for 1998-2000. Five-year mortality rates were 60% and 51%, respectively.

"Modern immunosuppression therapy seems to be associated with a decrease in the incidence" of systemic rheumatoid vasculitis, said Dr. Ntatsaki, "but has had no significant influence on clinical features, or outcome."

Whether the decrease in incidence can truly be attributed to methotrexate or improvements in RA treatment in general is questionable, suggested Dr. Deborah Symmons, professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England).

This decline in the incidence of rheumatoid vasculitis is not necessarily because rheumatoid arthritis treatments have improved, she said. "Perhaps it is just the natural history of rheumatoid arthritis that vasculitis is becoming rare. Clearly when people do get it they do just as badly as they ever did, and perhaps all this about methotrexate is completely coincidental."

Dr. Ntatsaki reported having no financial disclosures.

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.

At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.

There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.

These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).

"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).

Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.

Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.

Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.

A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.

With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.

Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).

Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).

Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.

They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.

The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.

GLASGOW, SCOTLAND – Upper-limb dysfunction in early rheumatoid arthritis patients can be significantly improved by a combined exercise and education strategy compared with usual care, based on preliminary findings of an assessor-blinded, randomized controlled trial.

Disability, function, hand grip strength, and self-efficacy assessed using the patient-rated Arthritis Self-Efficacy Scale (Arthritis Rheum. 1989;32:37-44) were all significantly (P less than .05) improved at 3 months in the EXTRA (Education and Exercise Upper-Limb Training in Early Rheumatoid Arthritis) study

"Whilst self-efficacy improved throughout the study, the [effects of the] other outcome measures did diminish, [and] efficacy was not sustained at 9 months," according to chief investigator for the trial Dr. Lindsay Bearne.

"However, the program is safe in people with early RA with moderate to high disease activity," Dr. Bearne, a lecturer in physiotherapy at King’s College London, added at the annual meeting of the British Society for Rheumatology.

The management approach being tested in the EXTRA study differs from other trials of exercise in RA in that it specifically addresses upper-limb dysfunction. The few previous trials that have been done focused on the effects of whole-body or lower-limb exercise or assessed only disability in the hand and wrist.

The aim of the EXTRA study, therefore, was to specifically look at the combined 12-week efficacy of a home-based exercise regimen supplemented with four group discussion and exercise sessions, versus usual care, for upper-limb rehabilitation in patients with early RA.

The primary hypothesis was that greater upper-limb function and less disability would be achieved with the exercise and education program than with usual care.

A total of 108 adults (82 women) with an average age of 55 years participated. All had early RA, with an average disease duration of 20 months. Patients who had received steroid injections in the previous 4 weeks or who had upper-limb surgery or physiotherapy in the past 6 months had been excluded.

The primary efficacy measure was improvement in upper-limb dysfunction assessed via the Disability of Arm, Shoulder, and Hand (DASH) outcome questionnaire. This is a 30-item disability/symptom scale with which patients rate their responses on a 5-point scale. An overall score from 0 (no disability) to 100 is obtained (BMC Musculoskeletal Disord. 2003;4:11).

Secondary assessments included hand-grip strength, self-efficacy, and a grip ability test for function. The 28-joint disease activity score (DAS28) was also used, and pain was assessed using a visual analog scale.

The daily home exercise program used in the study involved six simple exercises selected to suit the patient from an overall list of 16 exercises. The main "menu" of exercises selected to improve upper-limb strength and function was based on expert opinion and the published literature, Dr. Bearne explained, and included arm curls and squeezing a ball of putty.

DAS28 and pain scores at 3 months were both significantly lower (P less than .05) in the patients who had been randomized to the EXTRA program versus the usual care group. DAS28 and pain scores at baseline and at 9 months’ follow-up were not significantly different between the groups.

These data highlight that personalized, well-described global upper-limb exercises and a self-management program can help improve upper-limb dysfunction, if only temporarily.

"The challenge of sustaining long-term exercise remains," said Dr. Bearne.

"We appear to be able to motivate people to exercise, and to initiate exercise; [the difficulty is] to take that initial burst of enthusiasm and convert it to a longer-term habit."

Further data, including the results of a health economic evaluation, are expected from the EXTRA study.

Dr. Bearne reported no relevant financial disclosures. EXTRA is funded by the Chartered Society of Physiotherapy/Physiotherapy Research Foundation and sponsored by King’s College London.

GLASGOW, SCOTLAND – Upper-limb dysfunction in early rheumatoid arthritis patients can be significantly improved by a combined exercise and education strategy compared with usual care, based on preliminary findings of an assessor-blinded, randomized controlled trial.

Disability, function, hand grip strength, and self-efficacy assessed using the patient-rated Arthritis Self-Efficacy Scale (Arthritis Rheum. 1989;32:37-44) were all significantly (P less than .05) improved at 3 months in the EXTRA (Education and Exercise Upper-Limb Training in Early Rheumatoid Arthritis) study

"Whilst self-efficacy improved throughout the study, the [effects of the] other outcome measures did diminish, [and] efficacy was not sustained at 9 months," according to chief investigator for the trial Dr. Lindsay Bearne.

"However, the program is safe in people with early RA with moderate to high disease activity," Dr. Bearne, a lecturer in physiotherapy at King’s College London, added at the annual meeting of the British Society for Rheumatology.

The management approach being tested in the EXTRA study differs from other trials of exercise in RA in that it specifically addresses upper-limb dysfunction. The few previous trials that have been done focused on the effects of whole-body or lower-limb exercise or assessed only disability in the hand and wrist.

The aim of the EXTRA study, therefore, was to specifically look at the combined 12-week efficacy of a home-based exercise regimen supplemented with four group discussion and exercise sessions, versus usual care, for upper-limb rehabilitation in patients with early RA.

The primary hypothesis was that greater upper-limb function and less disability would be achieved with the exercise and education program than with usual care.

A total of 108 adults (82 women) with an average age of 55 years participated. All had early RA, with an average disease duration of 20 months. Patients who had received steroid injections in the previous 4 weeks or who had upper-limb surgery or physiotherapy in the past 6 months had been excluded.

The primary efficacy measure was improvement in upper-limb dysfunction assessed via the Disability of Arm, Shoulder, and Hand (DASH) outcome questionnaire. This is a 30-item disability/symptom scale with which patients rate their responses on a 5-point scale. An overall score from 0 (no disability) to 100 is obtained (BMC Musculoskeletal Disord. 2003;4:11).

Secondary assessments included hand-grip strength, self-efficacy, and a grip ability test for function. The 28-joint disease activity score (DAS28) was also used, and pain was assessed using a visual analog scale.

The daily home exercise program used in the study involved six simple exercises selected to suit the patient from an overall list of 16 exercises. The main "menu" of exercises selected to improve upper-limb strength and function was based on expert opinion and the published literature, Dr. Bearne explained, and included arm curls and squeezing a ball of putty.

DAS28 and pain scores at 3 months were both significantly lower (P less than .05) in the patients who had been randomized to the EXTRA program versus the usual care group. DAS28 and pain scores at baseline and at 9 months’ follow-up were not significantly different between the groups.

These data highlight that personalized, well-described global upper-limb exercises and a self-management program can help improve upper-limb dysfunction, if only temporarily.

"The challenge of sustaining long-term exercise remains," said Dr. Bearne.

"We appear to be able to motivate people to exercise, and to initiate exercise; [the difficulty is] to take that initial burst of enthusiasm and convert it to a longer-term habit."

Further data, including the results of a health economic evaluation, are expected from the EXTRA study.

Dr. Bearne reported no relevant financial disclosures. EXTRA is funded by the Chartered Society of Physiotherapy/Physiotherapy Research Foundation and sponsored by King’s College London.

GLASGOW, SCOTLAND – Upper-limb dysfunction in early rheumatoid arthritis patients can be significantly improved by a combined exercise and education strategy compared with usual care, based on preliminary findings of an assessor-blinded, randomized controlled trial.

Disability, function, hand grip strength, and self-efficacy assessed using the patient-rated Arthritis Self-Efficacy Scale (Arthritis Rheum. 1989;32:37-44) were all significantly (P less than .05) improved at 3 months in the EXTRA (Education and Exercise Upper-Limb Training in Early Rheumatoid Arthritis) study

"Whilst self-efficacy improved throughout the study, the [effects of the] other outcome measures did diminish, [and] efficacy was not sustained at 9 months," according to chief investigator for the trial Dr. Lindsay Bearne.

"However, the program is safe in people with early RA with moderate to high disease activity," Dr. Bearne, a lecturer in physiotherapy at King’s College London, added at the annual meeting of the British Society for Rheumatology.

The management approach being tested in the EXTRA study differs from other trials of exercise in RA in that it specifically addresses upper-limb dysfunction. The few previous trials that have been done focused on the effects of whole-body or lower-limb exercise or assessed only disability in the hand and wrist.

The aim of the EXTRA study, therefore, was to specifically look at the combined 12-week efficacy of a home-based exercise regimen supplemented with four group discussion and exercise sessions, versus usual care, for upper-limb rehabilitation in patients with early RA.

The primary hypothesis was that greater upper-limb function and less disability would be achieved with the exercise and education program than with usual care.

A total of 108 adults (82 women) with an average age of 55 years participated. All had early RA, with an average disease duration of 20 months. Patients who had received steroid injections in the previous 4 weeks or who had upper-limb surgery or physiotherapy in the past 6 months had been excluded.

The primary efficacy measure was improvement in upper-limb dysfunction assessed via the Disability of Arm, Shoulder, and Hand (DASH) outcome questionnaire. This is a 30-item disability/symptom scale with which patients rate their responses on a 5-point scale. An overall score from 0 (no disability) to 100 is obtained (BMC Musculoskeletal Disord. 2003;4:11).

Secondary assessments included hand-grip strength, self-efficacy, and a grip ability test for function. The 28-joint disease activity score (DAS28) was also used, and pain was assessed using a visual analog scale.

The daily home exercise program used in the study involved six simple exercises selected to suit the patient from an overall list of 16 exercises. The main "menu" of exercises selected to improve upper-limb strength and function was based on expert opinion and the published literature, Dr. Bearne explained, and included arm curls and squeezing a ball of putty.

DAS28 and pain scores at 3 months were both significantly lower (P less than .05) in the patients who had been randomized to the EXTRA program versus the usual care group. DAS28 and pain scores at baseline and at 9 months’ follow-up were not significantly different between the groups.

These data highlight that personalized, well-described global upper-limb exercises and a self-management program can help improve upper-limb dysfunction, if only temporarily.

"The challenge of sustaining long-term exercise remains," said Dr. Bearne.

"We appear to be able to motivate people to exercise, and to initiate exercise; [the difficulty is] to take that initial burst of enthusiasm and convert it to a longer-term habit."

Further data, including the results of a health economic evaluation, are expected from the EXTRA study.

Dr. Bearne reported no relevant financial disclosures. EXTRA is funded by the Chartered Society of Physiotherapy/Physiotherapy Research Foundation and sponsored by King’s College London.

GLASGOW, SCOTLAND – Early arthritis patients who are obese are less likely to achieve a good response to disease-modifying antirheumatic drugs in their first year of treatment than their lighter counterparts, judging from the results of a 212-patient study.

The median 28-joint count disease activity score (DAS28) was higher (3.1 vs. 2.6) and fewer patients achieved DAS28 remission (40.3% vs. 52.3%) comparing obese with normal-weight or underweight patients.

A good EULAR response was achieved by 40% of patient who were classified as obese vs. 58.5% of those classified as being of normal weight or underweight.

"There was not much difference in initial treatment across the whole cohort of patients, but at the endpoint of 1 year we found that the obese patients just were not responding as well," said Dr. Stephanie Ling in an interview at the annual meeting of the British Society for Rheumatology.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population."

"There are a number of reasons that could be behind this. It could be we are not adjusting the dose to weight, or it could be because of our hypothesis that inflammatory markers are higher in the obese patients anyway."

Dr. Ling of the University of Liverpool (England) and coworkers have previously assessed how obesity affects disease activity in rheumatoid arthritis (RA), finding that the higher the body mass index (BMI), the greater the DAS28 and inflammatory disease activity (Rheumatology News, May 2011, p. 34).

"When we broke down the disease activity score components, there was not much difference between obese and non-obese patients in the tender and swollen joint counts," she said.

"When you got down to the levels of the inflammatory markers in the blood, however, those were statistically significantly raised in the very obese patients." This could be influencing the response to treatment, and possibly explain the impaired response to disease-modifying antirheumatic drugs (DMARDs) that was seen in the present study (Rheumatology 2012;51:iii162–3, abstract P295).

The current investigation assessed the effects of obesity on disease activity in the first year of DMARD therapy in an inception cohort of RA patients who had a symptom duration of less than 1 year.

The mean age of patients was 57.7 years, 60.1% were female, and 71.2% were positive for anticitrullinated protein antibodies (ACPA). The median body mass index (BMI) was 27.5 kg/m², with a third (34%) of the cohort classified as being obese (BMI greater than 30).

At 1 year, the median DAS28 score for the entire cohort was 2.6, and 51% were in DAS28 remission; 58% had achieved a good EULAR response. When outcomes were split according to BMI, however, the obese patients did significantly worse.

The median DAS28 score in overweight (BMI 25-29.9) patients at 1 year was 2.4; 45% achieved DAS28 remission, and 66.7% achieved a good EULAR response.

A trend for association between obesity and high baseline DAS28 (greater than 5.1) was found (odds ratio, 1.7; 95% confidence interval, 0.9-3.1), which grew stronger when the analysis was limited to patients who were ACPA-positive (OR, 2.0; 95% CI, 1.0-4.0). However, ACPA-positivity by itself was not associated with treatment response at 1 year.

Inverse correlations between baseline obesity and DAS28 remission and EULAR response at 1 year were found to be more prominent in female than male patients.

"I think we definitely need to think about dosing according to weight instead of giving everyone the same dose," Dr. Ling suggested. Dosing by weight is done in pediatric but not adult practice.

Losing weight may also be of benefit but requires further investigation to see if this in itself could help improve the response to therapy. Anecdotally, Dr. Ling noted the case of a woman who had been on high-dose treatment and lost more than 238 pounds and subsequently went into remission, without further need for drug therapy.

Other work presented by Dr. Corrinne Ellis showed that obesity is linked to greater functional disability (Rheumatology 2012;51:iii163, abstract P296). Analysis of data on 803 patients (21% obese) with inflammatory polyarthritis in the Norfolk Arthritis Register (NOAR) revealed that baseline obesity was associated with higher disability, as determined by the Health Assessment Questionnaire (HAQ) at 1 year.

Perhaps the reason HAQ scores are higher in obese patients is because they are just too unfit or obese to exercise. Indeed, other research presented at this meeting showed that cardiorespiratory fitness assessed using a simple step test was low in patients with RA (Rheumatology 2012;51:iii162–3, abstract P80).

Cardiorespiratory fitness is an independent risk factor for heart disease and was found to be decreased in the study of 100 patients with RA regardless of whether traditional cardiovascular risk factors were also present. Cardiorespiratory fitness was linked to obesity and the metabolic syndrome.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population," according to Ms. Jennifer Cooney of the University of Bangor (Wales) and associates.

"Thus more attentions and understanding is required on addressing these factors than the traditional risk factors alone."

Dr. Ling reported no financial disclosures.

GLASGOW, SCOTLAND – Early arthritis patients who are obese are less likely to achieve a good response to disease-modifying antirheumatic drugs in their first year of treatment than their lighter counterparts, judging from the results of a 212-patient study.

The median 28-joint count disease activity score (DAS28) was higher (3.1 vs. 2.6) and fewer patients achieved DAS28 remission (40.3% vs. 52.3%) comparing obese with normal-weight or underweight patients.

A good EULAR response was achieved by 40% of patient who were classified as obese vs. 58.5% of those classified as being of normal weight or underweight.

"There was not much difference in initial treatment across the whole cohort of patients, but at the endpoint of 1 year we found that the obese patients just were not responding as well," said Dr. Stephanie Ling in an interview at the annual meeting of the British Society for Rheumatology.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population."

"There are a number of reasons that could be behind this. It could be we are not adjusting the dose to weight, or it could be because of our hypothesis that inflammatory markers are higher in the obese patients anyway."

Dr. Ling of the University of Liverpool (England) and coworkers have previously assessed how obesity affects disease activity in rheumatoid arthritis (RA), finding that the higher the body mass index (BMI), the greater the DAS28 and inflammatory disease activity (Rheumatology News, May 2011, p. 34).

"When we broke down the disease activity score components, there was not much difference between obese and non-obese patients in the tender and swollen joint counts," she said.

"When you got down to the levels of the inflammatory markers in the blood, however, those were statistically significantly raised in the very obese patients." This could be influencing the response to treatment, and possibly explain the impaired response to disease-modifying antirheumatic drugs (DMARDs) that was seen in the present study (Rheumatology 2012;51:iii162–3, abstract P295).

The current investigation assessed the effects of obesity on disease activity in the first year of DMARD therapy in an inception cohort of RA patients who had a symptom duration of less than 1 year.

The mean age of patients was 57.7 years, 60.1% were female, and 71.2% were positive for anticitrullinated protein antibodies (ACPA). The median body mass index (BMI) was 27.5 kg/m², with a third (34%) of the cohort classified as being obese (BMI greater than 30).

At 1 year, the median DAS28 score for the entire cohort was 2.6, and 51% were in DAS28 remission; 58% had achieved a good EULAR response. When outcomes were split according to BMI, however, the obese patients did significantly worse.

The median DAS28 score in overweight (BMI 25-29.9) patients at 1 year was 2.4; 45% achieved DAS28 remission, and 66.7% achieved a good EULAR response.

A trend for association between obesity and high baseline DAS28 (greater than 5.1) was found (odds ratio, 1.7; 95% confidence interval, 0.9-3.1), which grew stronger when the analysis was limited to patients who were ACPA-positive (OR, 2.0; 95% CI, 1.0-4.0). However, ACPA-positivity by itself was not associated with treatment response at 1 year.

Inverse correlations between baseline obesity and DAS28 remission and EULAR response at 1 year were found to be more prominent in female than male patients.

"I think we definitely need to think about dosing according to weight instead of giving everyone the same dose," Dr. Ling suggested. Dosing by weight is done in pediatric but not adult practice.

Losing weight may also be of benefit but requires further investigation to see if this in itself could help improve the response to therapy. Anecdotally, Dr. Ling noted the case of a woman who had been on high-dose treatment and lost more than 238 pounds and subsequently went into remission, without further need for drug therapy.

Other work presented by Dr. Corrinne Ellis showed that obesity is linked to greater functional disability (Rheumatology 2012;51:iii163, abstract P296). Analysis of data on 803 patients (21% obese) with inflammatory polyarthritis in the Norfolk Arthritis Register (NOAR) revealed that baseline obesity was associated with higher disability, as determined by the Health Assessment Questionnaire (HAQ) at 1 year.

Perhaps the reason HAQ scores are higher in obese patients is because they are just too unfit or obese to exercise. Indeed, other research presented at this meeting showed that cardiorespiratory fitness assessed using a simple step test was low in patients with RA (Rheumatology 2012;51:iii162–3, abstract P80).

Cardiorespiratory fitness is an independent risk factor for heart disease and was found to be decreased in the study of 100 patients with RA regardless of whether traditional cardiovascular risk factors were also present. Cardiorespiratory fitness was linked to obesity and the metabolic syndrome.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population," according to Ms. Jennifer Cooney of the University of Bangor (Wales) and associates.

"Thus more attentions and understanding is required on addressing these factors than the traditional risk factors alone."

Dr. Ling reported no financial disclosures.

GLASGOW, SCOTLAND – Early arthritis patients who are obese are less likely to achieve a good response to disease-modifying antirheumatic drugs in their first year of treatment than their lighter counterparts, judging from the results of a 212-patient study.

The median 28-joint count disease activity score (DAS28) was higher (3.1 vs. 2.6) and fewer patients achieved DAS28 remission (40.3% vs. 52.3%) comparing obese with normal-weight or underweight patients.

A good EULAR response was achieved by 40% of patient who were classified as obese vs. 58.5% of those classified as being of normal weight or underweight.

"There was not much difference in initial treatment across the whole cohort of patients, but at the endpoint of 1 year we found that the obese patients just were not responding as well," said Dr. Stephanie Ling in an interview at the annual meeting of the British Society for Rheumatology.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population."

"There are a number of reasons that could be behind this. It could be we are not adjusting the dose to weight, or it could be because of our hypothesis that inflammatory markers are higher in the obese patients anyway."

Dr. Ling of the University of Liverpool (England) and coworkers have previously assessed how obesity affects disease activity in rheumatoid arthritis (RA), finding that the higher the body mass index (BMI), the greater the DAS28 and inflammatory disease activity (Rheumatology News, May 2011, p. 34).

"When we broke down the disease activity score components, there was not much difference between obese and non-obese patients in the tender and swollen joint counts," she said.

"When you got down to the levels of the inflammatory markers in the blood, however, those were statistically significantly raised in the very obese patients." This could be influencing the response to treatment, and possibly explain the impaired response to disease-modifying antirheumatic drugs (DMARDs) that was seen in the present study (Rheumatology 2012;51:iii162–3, abstract P295).

The current investigation assessed the effects of obesity on disease activity in the first year of DMARD therapy in an inception cohort of RA patients who had a symptom duration of less than 1 year.

The mean age of patients was 57.7 years, 60.1% were female, and 71.2% were positive for anticitrullinated protein antibodies (ACPA). The median body mass index (BMI) was 27.5 kg/m², with a third (34%) of the cohort classified as being obese (BMI greater than 30).

At 1 year, the median DAS28 score for the entire cohort was 2.6, and 51% were in DAS28 remission; 58% had achieved a good EULAR response. When outcomes were split according to BMI, however, the obese patients did significantly worse.

The median DAS28 score in overweight (BMI 25-29.9) patients at 1 year was 2.4; 45% achieved DAS28 remission, and 66.7% achieved a good EULAR response.

A trend for association between obesity and high baseline DAS28 (greater than 5.1) was found (odds ratio, 1.7; 95% confidence interval, 0.9-3.1), which grew stronger when the analysis was limited to patients who were ACPA-positive (OR, 2.0; 95% CI, 1.0-4.0). However, ACPA-positivity by itself was not associated with treatment response at 1 year.

Inverse correlations between baseline obesity and DAS28 remission and EULAR response at 1 year were found to be more prominent in female than male patients.

"I think we definitely need to think about dosing according to weight instead of giving everyone the same dose," Dr. Ling suggested. Dosing by weight is done in pediatric but not adult practice.

Losing weight may also be of benefit but requires further investigation to see if this in itself could help improve the response to therapy. Anecdotally, Dr. Ling noted the case of a woman who had been on high-dose treatment and lost more than 238 pounds and subsequently went into remission, without further need for drug therapy.

Other work presented by Dr. Corrinne Ellis showed that obesity is linked to greater functional disability (Rheumatology 2012;51:iii163, abstract P296). Analysis of data on 803 patients (21% obese) with inflammatory polyarthritis in the Norfolk Arthritis Register (NOAR) revealed that baseline obesity was associated with higher disability, as determined by the Health Assessment Questionnaire (HAQ) at 1 year.

Perhaps the reason HAQ scores are higher in obese patients is because they are just too unfit or obese to exercise. Indeed, other research presented at this meeting showed that cardiorespiratory fitness assessed using a simple step test was low in patients with RA (Rheumatology 2012;51:iii162–3, abstract P80).

Cardiorespiratory fitness is an independent risk factor for heart disease and was found to be decreased in the study of 100 patients with RA regardless of whether traditional cardiovascular risk factors were also present. Cardiorespiratory fitness was linked to obesity and the metabolic syndrome.

"This study has highlighted the alarming levels of obesity and poor fitness in a typical well-controlled RA population," according to Ms. Jennifer Cooney of the University of Bangor (Wales) and associates.

"Thus more attentions and understanding is required on addressing these factors than the traditional risk factors alone."

Dr. Ling reported no financial disclosures.