ACR Annual Meeting 2011

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – The novel anti–tumor necrosis factor nanobody ATN-103 looks as if it will be moving on to phase III trials, based on the good efficacy and safety results of a phase IIA trial of more than 250 patients with rheumatoid arthritis.

"The 80-mg, every-4-weeks regimen was the one [dosage] that was consistently improved over placebo by ACR 20" (the American College of Rheumatology evaluation scale that reflects a 20% improvement in specified parameters), Dr. Roy M. Fleischmann said at the American College of Rheumatology annual meeting. In addition, this dosage group comprised the only patients to achieve significantly better responses on the ACR 50 and the ACR 70 criteria than was achieved by those taking placebo.

A nanobody is the smallest functional fragment of a naturally occurring, single-chain antibody, and ATN-103 (ozoralizumab) is just one-quarter the size of conventional TNF-blockers, Dr. Fleischmann noted. As a humanized bispecific nanobody, ATN-103 contains two human TNF-binding domains that are linked to a human serum albumin–binding domain to extend half-life.

The researchers conducted a double-blind, placebo-controlled, phase IIA proof-of-concept study that included 253 patients in three treatment groups, with roughly 40 patients at each dosage level. The 4-week dosing group received the active drug (a subcutaneous injection of 10 mg, 30 mg, or 80 mg) on day 1 of weeks 4, 8, and 12. The 8-week dosing group received either 10 mg or 80 mg of the drug on day 1 of each 8-week period. Those in the placebo group received a placebo injection on day 1 of weeks 4, 8, and 12.

All of the patients had active RA (defined as at least six swollen and at least six tender joints) at the time of screening and at baseline, despite having been treated with methotrexate for at least 12 weeks. To qualify for the study, they had to meet the 1987 revised criteria for RA at least 24 weeks prior to screening, to be within ACR functional class I-III, and to have a C-reactive protein level of at least 8 mg/L. In addition, their methotrexate dose (7.5-25 mg) and route of administration had to be stable for at least 6 weeks prior to baseline. The patients were stratified by prior TNF-inhibitor use; two-thirds of them were naive to TNF-blockers.

The primary outcome of this study was ACR 20 at 16 weeks. Secondary end points were improvements over placebo in clinical scores, DAS28 (Disease Activity Score based on a 28-joint count), ACR 50, ACR 70, and EULAR responses at week 16.

The ACR criteria are used to evaluate improvement in tender or swollen joint counts, as well as improvement in three of the following five parameters: acute phase reactant, patient assessment, physician assessment, pain scale, and disability/functional questionnaire scores. The EULAR response includes not only change in disease activity but also current disease activity.

"The safety profile looked relatively clean," said Dr. Fleischmann of the Metroplex Clinical Research Center in Dallas. Of 43 patients in the 80-mg, every-4-weeks group, there were 23 adverse reactions, of which infections were the most common at 19% – a safety profile similar to that of other anti-TNFs. One patient did withdraw from this group because of adverse events (AEs), but there were no deaths, no dose-limiting toxicities, and no clinically significant increases in AEs or serious AEs with increasing dose. Overall, 13 patients reported 17 serious AEs, of which respiratory tract infections and disorders were the most common.

The trial was sponsored by Pfizer, and all of the authors noted significant financial relationships with the company.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – A causal relationship between rheumatoid arthritis and periodontal disease has not been confirmed, but recent data support the concept of a bi-directional relationship between the two.

In fact, a number of investigators have attempted to characterize the relationship between rheumatoid arthritis (RA) and periodontal disease. While most research confirms that one exists, the strength and extent of that relationship remain unclear, Michele Ravenel, D.M.D., said at the annual meeting of the American College of Rheumatology.

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," Dr. Ravenel said. But in her own review of the literature, the only consistency she found was inconsistency, said Dr. Ravenel.

In one recent case-control study involving 57 RA patients and 52 healthy subjects, those with RA were found to have significantly greater odds of having periodontitis after adjusting for a number of variables including RA status, age, sex, alcohol use, and body mass index (J. Periodontol. 2008;79:979-86).

"Periodontal disease and RA do share similar pathologic mechanisms, and the relationship appears to be bi-directional," said Michele Ravenel, D.M.D.

And in another recent study, 65 RA patients all were found to have some form of periodontal disease, which was moderate or severe in most cases. However, rheumatoid factor levels were not found to have any influence on oral bacterial composition and/or concentration – or on severity of periodontal disease (J. Periodontol. 2011;82:1424-32).

In yet another study of patients with both moderate to severe RA and severe periodontal disease, outcomes were compared in 10 patients on no treatment, 10 on periodontal therapy, 10 on anti-TNF-alpha therapy, and 10 on both periodontal therapy and anti-TNF-alpha therapy (J. Periodontol. 2009;80:535-40). Patients who were receiving treatment for periodontal disease – either with or without anti-TNF-alpha therapy for their RA – experienced significantly greater improvements in both the periodontal disease and the RA, compared with those not on periodontal therapy, said Dr. Ravenel of the Medical University of South Carolina, Charleston.

As for the role of periodontal pathogens in RA, findings from two recent case-control studies showed that serum antibodies to known periodontal pathogens were found more frequently in those with RA and periodontal disease than in controls (MedGenMed. 2005;7:2;Clin. Exp. Rheumatol. 2006;24:656-63).

In a cross-sectional study, bacterial DNA of some of the more virulent periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia, were identified in synovial fluid of RA-affected joints (J. Clin. Periodontol. 2009;1004-10).

In another study, which was presented separately at the 2011 annual meeting of the ACR, Dr. Jose U. Scher reported on a potentially important role for "a single species-level operational taxonomic unit belonging to the genus Porphyromonas and homologous to P. gingivalis," which he said could explain the link between RA and periodontal disease.

The particular Porphyromonas species was significantly more prevalent and more abundant in 25 patients with new-onset, never-treated RA, compared with 27 patients with established disease, and 14 healthy controls. That species accounted for nearly 10% of the bacteria in the new-onset RA patients, compared with about 3% and 4% of the bacteria in control patients and patients with chronic established disease, respectively, said Dr. Scher, of New York University Hospital for Joint Diseases.

More than 90% of the patients with new-onset RA in the study had moderate to severe periodontal disease. The study findings showed that the oral microbiome in these patients – all of whom were anticitrullinated peptide antibody-positive – is distinct at disease onset and characterized by an abundance of the virulent Porphyromonas species.

Further identification of the species may provide new insight regarding the reported link between RA and periodontal disease, he concluded.

Additional research should include strict adherence to diagnostic criteria for both diseases, Dr. Ravenel said.

Dr. Ravenel and Dr. Scher both said they have no relevant disclosures.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

CHICAGO – Metabolic syndrome is significantly more common in patients with psoriatic arthritis than in those with rheumatoid arthritis, based on data from nearly 2,000 adults.

Previous studies have suggested that metabolic syndrome is associated with "a state of chronic, low-grade inflammation," said Dr. Asena Bahce-Altuntas of Albert Einstein College of Medicine in New York.

"Since psoriatic arthritis [PsA] is characterized by inflammation of both skin and joints, we may be underestimating this cardiovascular risk in PsA," she said at the annual meeting of the American College of Rheumatology.

To compare the prevalence of metabolic syndrome in patients with PsA versus rheumatoid arthritis (RA), Dr. Bahce-Altuntas and her colleagues used data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a prospective, observational cohort including 4,014 patients with PsA and 25,976 patients with RA in academic and private practices throughout the United States. Lipid profile data were available for 1,956 patients from the CORRONA registry: 294 with PsA and 1,662 with RA.

Overall, 27% of PsA patients met criteria for metabolic syndrome, compared with 19% of RA patients. In addition, several specific components of metabolic syndrome were significantly more common in PsA patients.

In particular, significantly more PsA patients than RA patients had triglycerides greater than 150 mg/dL (38% vs. 28%).

Significantly more PsA patients than RA patients were male (54% vs. 23%, respectively), and the mean age was significantly greater in RA patients than in PsA patients (62 years vs. 56 years, respectively). However, after age, sex, and ethnicity were controlled for, the odds of metabolic syndrome remained significantly higher for PsA patients (odds ratio, 1.44).

Metabolic syndrome was defined as a body mass index greater than 30 kg/m² and any two of the following criteria: triglycerides greater than 150 mg/dL, HDL less than 40 mg/dL for men or less than 50 mg/dL for women, a diagnosis of hypertension, or a diagnosis of diabetes.

In a subanalysis of obese patients (133 PsA patients and 654 RA patients with a BMI greater than 30), the prevalence of metabolic syndrome remained significantly higher in PsA patients (60%) than in RA patients (49%), as did the prevalence of patients with triglycerides greater than 150 mg/dL (51% vs. 39%).

The study was limited by the relatively small sample of PsA patients, and by the modified metabolic syndrome criteria that may have underestimated the prevalence of metabolic syndrome in both groups, said Dr. Bahce-Altuntas.

However, the results suggest that metabolic syndrome and its components are significantly more common in PsA than in RA. "High triglycerides appear to drive the estimated increase in risk of metabolic syndrome in PsA vs. RA," she noted.

The combination of skin and joint inflammation in PsA may contribute to the increased frequency of metabolic syndrome in these patients, but more research is needed, Dr. Bahce-Altuntas said.

Meanwhile, "more intensive interventions to modify these risk factors are warranted in PsA patients in order to reduce cardiovascular morbidity and mortality," she said.

The following companies have supported CORRONA through contracted subscriptions over the past 2 years: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Genentech, Lilly, Pfizer, and Roche. Dr. Bahce-Altuntas had no financial conflicts to disclose.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Chatzidionysiou disclosed being a consultant to Roche.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Chatzidionysiou disclosed being a consultant to Roche.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Chatzidionysiou disclosed being a consultant to Roche.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Information about the relative risks of knee OA as a result of sports participation is essential to help develop prevention strategies and shape public health messages, said Jeffrey Driban, Ph.D., who presented the findings at the annual meeting of the American College of Rheumatology.

Dr. Driban and his colleagues at Tufts Medical Center in Boston analyzed 16 studies that identified OA rates in elite and recreational athletes participating in a range of sports including running, soccer, and wrestling. In general, the prevalence of knee OA was 8.4% among the 3,192 athletes of any level, compared with 9.1% among the 3,485 nonathletes, Dr. Driban said.

However, the risk of knee OA is sport-specific, Dr. Driban said. Compared with nonathletes, soccer players at elite and nonelite levels were at increased risk of knee OA (relative risk, 4.4), as were elite athletes competing in distance running (3.2), weight lifting (6.4), and wrestling (3.7). Elite athletes were defined as those competing at the national, Olympic, or professional level; nonelite athletes were those competing at the recreational or scholastic level.

The results were limited by the lack of adequate data on women and injury histories for the study participants. However, the data are encouraging and suggest that knee OA risk generally is not elevated for most recreational athletes, said Dr. Driban.

"For individuals who are interested in pursuing the health benefits of physical activity, sports participation can be a healthy way of getting those benefits," Dr. Driban emphasized.

However, anyone who is especially concerned about reducing their risk for OA should opt for low-impact, noncontact sports, he said. Elite athletes in high-risk sports can take steps to reduce their risk, such as treating injuries promptly and maintaining a healthy weight and lifestyle when they retire from competition, he added.

Dr. Driban reported having no financial conflicts of interest.

Information about the relative risks of knee OA as a result of sports participation is essential to help develop prevention strategies and shape public health messages, said Jeffrey Driban, Ph.D., who presented the findings at the annual meeting of the American College of Rheumatology.

Dr. Driban and his colleagues at Tufts Medical Center in Boston analyzed 16 studies that identified OA rates in elite and recreational athletes participating in a range of sports including running, soccer, and wrestling. In general, the prevalence of knee OA was 8.4% among the 3,192 athletes of any level, compared with 9.1% among the 3,485 nonathletes, Dr. Driban said.

However, the risk of knee OA is sport-specific, Dr. Driban said. Compared with nonathletes, soccer players at elite and nonelite levels were at increased risk of knee OA (relative risk, 4.4), as were elite athletes competing in distance running (3.2), weight lifting (6.4), and wrestling (3.7). Elite athletes were defined as those competing at the national, Olympic, or professional level; nonelite athletes were those competing at the recreational or scholastic level.

The results were limited by the lack of adequate data on women and injury histories for the study participants. However, the data are encouraging and suggest that knee OA risk generally is not elevated for most recreational athletes, said Dr. Driban.

"For individuals who are interested in pursuing the health benefits of physical activity, sports participation can be a healthy way of getting those benefits," Dr. Driban emphasized.

However, anyone who is especially concerned about reducing their risk for OA should opt for low-impact, noncontact sports, he said. Elite athletes in high-risk sports can take steps to reduce their risk, such as treating injuries promptly and maintaining a healthy weight and lifestyle when they retire from competition, he added.

Dr. Driban reported having no financial conflicts of interest.

Information about the relative risks of knee OA as a result of sports participation is essential to help develop prevention strategies and shape public health messages, said Jeffrey Driban, Ph.D., who presented the findings at the annual meeting of the American College of Rheumatology.

Dr. Driban and his colleagues at Tufts Medical Center in Boston analyzed 16 studies that identified OA rates in elite and recreational athletes participating in a range of sports including running, soccer, and wrestling. In general, the prevalence of knee OA was 8.4% among the 3,192 athletes of any level, compared with 9.1% among the 3,485 nonathletes, Dr. Driban said.

However, the risk of knee OA is sport-specific, Dr. Driban said. Compared with nonathletes, soccer players at elite and nonelite levels were at increased risk of knee OA (relative risk, 4.4), as were elite athletes competing in distance running (3.2), weight lifting (6.4), and wrestling (3.7). Elite athletes were defined as those competing at the national, Olympic, or professional level; nonelite athletes were those competing at the recreational or scholastic level.

The results were limited by the lack of adequate data on women and injury histories for the study participants. However, the data are encouraging and suggest that knee OA risk generally is not elevated for most recreational athletes, said Dr. Driban.

"For individuals who are interested in pursuing the health benefits of physical activity, sports participation can be a healthy way of getting those benefits," Dr. Driban emphasized.

However, anyone who is especially concerned about reducing their risk for OA should opt for low-impact, noncontact sports, he said. Elite athletes in high-risk sports can take steps to reduce their risk, such as treating injuries promptly and maintaining a healthy weight and lifestyle when they retire from competition, he added.

Dr. Driban reported having no financial conflicts of interest.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This is an investigator led initiative, supported by Roche.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This is an investigator led initiative, supported by Roche.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This is an investigator led initiative, supported by Roche.

CHICAGO – Early detection of incident systemic sclerosis–associated pulmonary arterial hypertension enhanced survival in a prospective cohort study of 131 patients from the multicenter PHAROS, according to data presented at the annual meeting of the American College of Rheumatology.

The survival rates for patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension who were enrolled in PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) "were better than for other recently described cohorts, with 1- and 3-year survival of 93% and 75%, respectively," said principal investigator Dr. Lorinda Chung of the department of immunology and rheumatology at Stanford (Calif.) University Medical Center.

"This may be due to the fact that we are screening our patients with [echocardiography and pulmonary function tests], and detecting their disease earlier, perhaps at a less severe stage," she said.

Furthermore, 17% of deaths in this cohort were not related to pulmonary arterial hypertension (PAH), suggesting that rheumatologists should remain involved in care even after patients are diagnosed with PAH, said Dr. Chung.

"Causes of death can be related to their underlying scleroderma or its complications," she said.

The independent predictors of death included functional class IV status, age greater than 60, male sex, and low (less than 39%) diffusion lung carbon monoxide, according to findings from a multivariate analysis.

PHAROS is a multicenter, U.S.-based prospective registry of SSc patients at high risk for PAH, or with definite pulmonary hypertension diagnosed by right heart catheterization within 6 months of enrollment. Of 434 patients enrolled in PHAROS, 131 had PAH.

Despite the availability of several therapies specific to pulmonary arterial hypertension, findings from recent studies of patients with incident scleroderma-associated PAH suggest that 1-year survival rates are as low as 72%-86% and 3-year survival rates are as low as 39%-67%.

This analysis included only patients with World Health Organization group I PAH, defined as mean pulmonary arterial pressure greater than 25 mm Hg and pulmonary capillary wedge pressure less than or equal to 15 mm Hg. Patients were excluded if they were found to have significant interstitial lung disease, defined as severe fibrosis on high-resolution CT or moderate fibrosis and a forced vital capacity less than 60% predicted.

Kaplan-Meier curves were used to estimate survival from the time of the diagnostic right heart catheterization, and Cox regression models were used to identify significant predictors of mortality.

The mean age of the 131 patients with PAH was 60.4±10.4 years, and most were female (84%) and white (82%). Fully 70% had limited cutaneous disease. Disease duration from the first Raynaud’s symptom was about 14.5 years and from the first non-Raynaud’s symptom was about 10 years.

"About a third of the patients had anticentromere antibodies and about a quarter had a nucleolar pattern on the ANA [antinuclear antibodies]," said Dr. Chung.

Over a mean follow-up period of 2.0 (1.4) years, 24 patients (18%) died. For the majority of those patients (20, or 83%), the cause of death was PAH or multiorgan failure, and the other four deaths were not related to PAH. In patients with incident SSc-associated PAH, 92.9 % survived at 1 year, 87.7 % at 2 years, and 74.8% at 3 years.

For the sake of comparison, Dr. Chung cited estimates from REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management), a U.S.-based prospective registry of patients with PAH, which includes a subgroup of patients with scleroderma. The majority of patients with incident SSc-associated PAH in the REVEAL registry were functional class III and IV at the time of PAH diagnosis, and their 3-year survival was only 54% – more than 20% less than patients in the PHAROS registry.

However, she said in the PHAROS cohort, "patients in functional class IV at enrollment had much poorer survival compared to those who were in functional classes I, II, or III." SSc-associated PAH patients with low diffusing capacity also had poorer survival. "The median value for the diffusion lung carbon monoxide was 39% predicted, and patients who had values below the median at enrollment experienced much poorer survival," she said.

Better survival was seen in systemic sclerosis–associated pulmonary arterial hypertension patients enrolled in the PHAROS registry.

PHAROS is an investigator-initiated study initially funded by Actelion, the Scleroderma Foundation, and the Sibley Foundation, with ongoing funding by Gilead. Dr. Chung reported financial relationships with Actelion, Gilead, Pfizer and United Therapeutics.

CHICAGO – Early detection of incident systemic sclerosis–associated pulmonary arterial hypertension enhanced survival in a prospective cohort study of 131 patients from the multicenter PHAROS, according to data presented at the annual meeting of the American College of Rheumatology.

The survival rates for patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension who were enrolled in PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) "were better than for other recently described cohorts, with 1- and 3-year survival of 93% and 75%, respectively," said principal investigator Dr. Lorinda Chung of the department of immunology and rheumatology at Stanford (Calif.) University Medical Center.

"This may be due to the fact that we are screening our patients with [echocardiography and pulmonary function tests], and detecting their disease earlier, perhaps at a less severe stage," she said.

Furthermore, 17% of deaths in this cohort were not related to pulmonary arterial hypertension (PAH), suggesting that rheumatologists should remain involved in care even after patients are diagnosed with PAH, said Dr. Chung.

"Causes of death can be related to their underlying scleroderma or its complications," she said.

The independent predictors of death included functional class IV status, age greater than 60, male sex, and low (less than 39%) diffusion lung carbon monoxide, according to findings from a multivariate analysis.

PHAROS is a multicenter, U.S.-based prospective registry of SSc patients at high risk for PAH, or with definite pulmonary hypertension diagnosed by right heart catheterization within 6 months of enrollment. Of 434 patients enrolled in PHAROS, 131 had PAH.

Despite the availability of several therapies specific to pulmonary arterial hypertension, findings from recent studies of patients with incident scleroderma-associated PAH suggest that 1-year survival rates are as low as 72%-86% and 3-year survival rates are as low as 39%-67%.

This analysis included only patients with World Health Organization group I PAH, defined as mean pulmonary arterial pressure greater than 25 mm Hg and pulmonary capillary wedge pressure less than or equal to 15 mm Hg. Patients were excluded if they were found to have significant interstitial lung disease, defined as severe fibrosis on high-resolution CT or moderate fibrosis and a forced vital capacity less than 60% predicted.

Kaplan-Meier curves were used to estimate survival from the time of the diagnostic right heart catheterization, and Cox regression models were used to identify significant predictors of mortality.

The mean age of the 131 patients with PAH was 60.4±10.4 years, and most were female (84%) and white (82%). Fully 70% had limited cutaneous disease. Disease duration from the first Raynaud’s symptom was about 14.5 years and from the first non-Raynaud’s symptom was about 10 years.

"About a third of the patients had anticentromere antibodies and about a quarter had a nucleolar pattern on the ANA [antinuclear antibodies]," said Dr. Chung.

Over a mean follow-up period of 2.0 (1.4) years, 24 patients (18%) died. For the majority of those patients (20, or 83%), the cause of death was PAH or multiorgan failure, and the other four deaths were not related to PAH. In patients with incident SSc-associated PAH, 92.9 % survived at 1 year, 87.7 % at 2 years, and 74.8% at 3 years.

For the sake of comparison, Dr. Chung cited estimates from REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management), a U.S.-based prospective registry of patients with PAH, which includes a subgroup of patients with scleroderma. The majority of patients with incident SSc-associated PAH in the REVEAL registry were functional class III and IV at the time of PAH diagnosis, and their 3-year survival was only 54% – more than 20% less than patients in the PHAROS registry.

However, she said in the PHAROS cohort, "patients in functional class IV at enrollment had much poorer survival compared to those who were in functional classes I, II, or III." SSc-associated PAH patients with low diffusing capacity also had poorer survival. "The median value for the diffusion lung carbon monoxide was 39% predicted, and patients who had values below the median at enrollment experienced much poorer survival," she said.

Better survival was seen in systemic sclerosis–associated pulmonary arterial hypertension patients enrolled in the PHAROS registry.

PHAROS is an investigator-initiated study initially funded by Actelion, the Scleroderma Foundation, and the Sibley Foundation, with ongoing funding by Gilead. Dr. Chung reported financial relationships with Actelion, Gilead, Pfizer and United Therapeutics.

CHICAGO – Early detection of incident systemic sclerosis–associated pulmonary arterial hypertension enhanced survival in a prospective cohort study of 131 patients from the multicenter PHAROS, according to data presented at the annual meeting of the American College of Rheumatology.

The survival rates for patients with incident systemic sclerosis (SSc)–associated pulmonary arterial hypertension who were enrolled in PHAROS (Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma) "were better than for other recently described cohorts, with 1- and 3-year survival of 93% and 75%, respectively," said principal investigator Dr. Lorinda Chung of the department of immunology and rheumatology at Stanford (Calif.) University Medical Center.

"This may be due to the fact that we are screening our patients with [echocardiography and pulmonary function tests], and detecting their disease earlier, perhaps at a less severe stage," she said.

Furthermore, 17% of deaths in this cohort were not related to pulmonary arterial hypertension (PAH), suggesting that rheumatologists should remain involved in care even after patients are diagnosed with PAH, said Dr. Chung.

"Causes of death can be related to their underlying scleroderma or its complications," she said.

The independent predictors of death included functional class IV status, age greater than 60, male sex, and low (less than 39%) diffusion lung carbon monoxide, according to findings from a multivariate analysis.

PHAROS is a multicenter, U.S.-based prospective registry of SSc patients at high risk for PAH, or with definite pulmonary hypertension diagnosed by right heart catheterization within 6 months of enrollment. Of 434 patients enrolled in PHAROS, 131 had PAH.

Despite the availability of several therapies specific to pulmonary arterial hypertension, findings from recent studies of patients with incident scleroderma-associated PAH suggest that 1-year survival rates are as low as 72%-86% and 3-year survival rates are as low as 39%-67%.

This analysis included only patients with World Health Organization group I PAH, defined as mean pulmonary arterial pressure greater than 25 mm Hg and pulmonary capillary wedge pressure less than or equal to 15 mm Hg. Patients were excluded if they were found to have significant interstitial lung disease, defined as severe fibrosis on high-resolution CT or moderate fibrosis and a forced vital capacity less than 60% predicted.

Kaplan-Meier curves were used to estimate survival from the time of the diagnostic right heart catheterization, and Cox regression models were used to identify significant predictors of mortality.

The mean age of the 131 patients with PAH was 60.4±10.4 years, and most were female (84%) and white (82%). Fully 70% had limited cutaneous disease. Disease duration from the first Raynaud’s symptom was about 14.5 years and from the first non-Raynaud’s symptom was about 10 years.

"About a third of the patients had anticentromere antibodies and about a quarter had a nucleolar pattern on the ANA [antinuclear antibodies]," said Dr. Chung.

Over a mean follow-up period of 2.0 (1.4) years, 24 patients (18%) died. For the majority of those patients (20, or 83%), the cause of death was PAH or multiorgan failure, and the other four deaths were not related to PAH. In patients with incident SSc-associated PAH, 92.9 % survived at 1 year, 87.7 % at 2 years, and 74.8% at 3 years.

For the sake of comparison, Dr. Chung cited estimates from REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management), a U.S.-based prospective registry of patients with PAH, which includes a subgroup of patients with scleroderma. The majority of patients with incident SSc-associated PAH in the REVEAL registry were functional class III and IV at the time of PAH diagnosis, and their 3-year survival was only 54% – more than 20% less than patients in the PHAROS registry.

However, she said in the PHAROS cohort, "patients in functional class IV at enrollment had much poorer survival compared to those who were in functional classes I, II, or III." SSc-associated PAH patients with low diffusing capacity also had poorer survival. "The median value for the diffusion lung carbon monoxide was 39% predicted, and patients who had values below the median at enrollment experienced much poorer survival," she said.

Better survival was seen in systemic sclerosis–associated pulmonary arterial hypertension patients enrolled in the PHAROS registry.

PHAROS is an investigator-initiated study initially funded by Actelion, the Scleroderma Foundation, and the Sibley Foundation, with ongoing funding by Gilead. Dr. Chung reported financial relationships with Actelion, Gilead, Pfizer and United Therapeutics.