Ankylosing spondylitis

MADRID – An international team has developed a new composite health index specifically for use in patients with ankylosing spondylitis.

The Assessment of SpondyloArthritis International Society Health Index (ASAS HI) is based on the ICF (International Classification of Functioning, Disability and Health) and includes 17 dichotomous items that ask about patients’ levels of pain, emotional functioning, sleep habits, sexual function, mobility, self-care, life in the community, and employment. The ICF is a comprehensive and already well-recognized and validated means of classifying and describing functioning, disability, and health in a systematic way,

The tool has yet to be "field tested" to see if it can measure changes in health status in response to treatment, Dr. Uta Kiltz said at the annual European Congress of Rheumatology.

Dr. Kiltz, of Rheumazentrum Ruhrgebiet, Herne, Germany, noted that the development of the tool involved five key stages. These have been outlined previously (Rheumatology 2011;50:894-8) and included a preparatory stage in which potential items for inclusion were identified. Dr. Kiltz and her colleagues considered a total of 251 items obtained from more than 60 existing questionnaires, such as the BASFI (Bath Ankylosing Spondylitis Functional Index), the Dougados Functional Index, and the AS Quality of Life Questionnaire.

The investigators then conducted an international, cross-sectional study involving 1,915 patients with AS (mean age, 51 years). In this second phase, they sent a postal survey to patients to ask about various parameters. An expert committee then assessed the results in the third phase and selected 50 items for possible inclusion in the final model. The penultimate stage in the development process involved sending a second postal survey to 628 patients with AS (mean age, 48.5 years).

In the final stage, an expert consensus meeting was held in which the final 17-item tool was agreed upon (Ann. Rheum. Dis. 2013;72:124).

"ASAS HI is a new composite index that captures relevant information on the health status of patients with AS," Dr. Kiltz said. "It is the first disease-specific index which is based on the ICF, and the items represent a whole range of abilities as defined by the ICF."

ASAS HI could eventually be used in clinical trials and clinical practice as a new composite index that captures relevant information on the health status of patients, Dr. Kiltz suggested.

"We are now doing a field test to test the 17 items in a wider range of patients," she said. After this is completed, the specifics of the tool will be published.

Dr. Kiltz had no conflicts of interest.

MADRID – An international team has developed a new composite health index specifically for use in patients with ankylosing spondylitis.

The Assessment of SpondyloArthritis International Society Health Index (ASAS HI) is based on the ICF (International Classification of Functioning, Disability and Health) and includes 17 dichotomous items that ask about patients’ levels of pain, emotional functioning, sleep habits, sexual function, mobility, self-care, life in the community, and employment. The ICF is a comprehensive and already well-recognized and validated means of classifying and describing functioning, disability, and health in a systematic way,

The tool has yet to be "field tested" to see if it can measure changes in health status in response to treatment, Dr. Uta Kiltz said at the annual European Congress of Rheumatology.

Dr. Kiltz, of Rheumazentrum Ruhrgebiet, Herne, Germany, noted that the development of the tool involved five key stages. These have been outlined previously (Rheumatology 2011;50:894-8) and included a preparatory stage in which potential items for inclusion were identified. Dr. Kiltz and her colleagues considered a total of 251 items obtained from more than 60 existing questionnaires, such as the BASFI (Bath Ankylosing Spondylitis Functional Index), the Dougados Functional Index, and the AS Quality of Life Questionnaire.

The investigators then conducted an international, cross-sectional study involving 1,915 patients with AS (mean age, 51 years). In this second phase, they sent a postal survey to patients to ask about various parameters. An expert committee then assessed the results in the third phase and selected 50 items for possible inclusion in the final model. The penultimate stage in the development process involved sending a second postal survey to 628 patients with AS (mean age, 48.5 years).

In the final stage, an expert consensus meeting was held in which the final 17-item tool was agreed upon (Ann. Rheum. Dis. 2013;72:124).

"ASAS HI is a new composite index that captures relevant information on the health status of patients with AS," Dr. Kiltz said. "It is the first disease-specific index which is based on the ICF, and the items represent a whole range of abilities as defined by the ICF."

ASAS HI could eventually be used in clinical trials and clinical practice as a new composite index that captures relevant information on the health status of patients, Dr. Kiltz suggested.

"We are now doing a field test to test the 17 items in a wider range of patients," she said. After this is completed, the specifics of the tool will be published.

Dr. Kiltz had no conflicts of interest.

MADRID – An international team has developed a new composite health index specifically for use in patients with ankylosing spondylitis.

The Assessment of SpondyloArthritis International Society Health Index (ASAS HI) is based on the ICF (International Classification of Functioning, Disability and Health) and includes 17 dichotomous items that ask about patients’ levels of pain, emotional functioning, sleep habits, sexual function, mobility, self-care, life in the community, and employment. The ICF is a comprehensive and already well-recognized and validated means of classifying and describing functioning, disability, and health in a systematic way,

The tool has yet to be "field tested" to see if it can measure changes in health status in response to treatment, Dr. Uta Kiltz said at the annual European Congress of Rheumatology.

Dr. Kiltz, of Rheumazentrum Ruhrgebiet, Herne, Germany, noted that the development of the tool involved five key stages. These have been outlined previously (Rheumatology 2011;50:894-8) and included a preparatory stage in which potential items for inclusion were identified. Dr. Kiltz and her colleagues considered a total of 251 items obtained from more than 60 existing questionnaires, such as the BASFI (Bath Ankylosing Spondylitis Functional Index), the Dougados Functional Index, and the AS Quality of Life Questionnaire.

The investigators then conducted an international, cross-sectional study involving 1,915 patients with AS (mean age, 51 years). In this second phase, they sent a postal survey to patients to ask about various parameters. An expert committee then assessed the results in the third phase and selected 50 items for possible inclusion in the final model. The penultimate stage in the development process involved sending a second postal survey to 628 patients with AS (mean age, 48.5 years).

In the final stage, an expert consensus meeting was held in which the final 17-item tool was agreed upon (Ann. Rheum. Dis. 2013;72:124).

"ASAS HI is a new composite index that captures relevant information on the health status of patients with AS," Dr. Kiltz said. "It is the first disease-specific index which is based on the ICF, and the items represent a whole range of abilities as defined by the ICF."

ASAS HI could eventually be used in clinical trials and clinical practice as a new composite index that captures relevant information on the health status of patients, Dr. Kiltz suggested.

"We are now doing a field test to test the 17 items in a wider range of patients," she said. After this is completed, the specifics of the tool will be published.

Dr. Kiltz had no conflicts of interest.

MADRID – High baseline disease activity and serum C-reactive protein levels may be a means of predicting which patients with spondyloarthropathy are likely to develop cardiovascular disease.

Both were linked to arterial stiffness, a surrogate marker for heart disease, in a 5-year follow-up study of 103 hospital-recruited patients with ankylosing spondylitis (Ann. Rheum. Dis 2013;72[Suppls3]:125).

"Reducing disease activity may [therefore] be a viable way of reducing excess cardiovascular disease [CVD] in ankylosing spondylitis [AS]," study investigator Dr. Inger Jorid Berg said at the annual European Congress of Rheumatology.

Baseline disease severity was measured with the ankylosing spondylitis disease activity score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). However, only ASDAS predicted the development of increased arterial stiffness from high baseline disease activity.

"Several studies have shown that patients with ankylosing spondylitis have [an] increased [risk] of cardiovascular disease," noted Dr. Berg, a consultant rheumatologist at Diakonhjemmet Hospital in Oslo. This includes atherosclerotic CVD, she observed, which previous research has linked to having a high ASDAS.

The present investigation explored whether high baseline ASDAS could be used to predict increased arterial stiffness as measured with the Augmentation Index (AIx). The investigators measured arterial stiffness using the SphygmoCor apparatus, a noninvasive system that involves placement of a probe at the radial artery.

Patients included in the study had AS confirmed via modified New York criteria and had undergone assessments in 2003 and again in 2008-2009. The assessments included clinical examinations and questionnaires to assess baseline disease severity and blood tests to measure C-reactive protein (CRP) levels and the erythrocyte sedimentation rate (ESR).

At the baseline assessment in 2003, the patients (56% men) had a mean age of 48 years, and a mean body mass index of 24.4 kg/m². A quarter of the patients were smokers. Their mean ASDAS was 2.5 and their mean BASDAI was 4.1, indicating moderate disease activity. There were only a few known cardiovascular comorbidities present, which included hypertension (5%) and diabetes (3%), although there were more patients with comorbidities at the later assessment. Most (83%) patients were taking nonsteroidal antiinflammatory drugs. Another 17% were using disease-modifying antirheumatic drugs, and very few (2%) were using tumor necrosis factor inhibitors.

"There was a clear trend in increasing CRP values, ESR values, and ASDAS," Dr. Berg said. This was significant for CRP (P = .004) and ASDAS (P = .01), and borderline significant for ESR (P = .05).

Multivariate analysis showed that CRP and ASDAS were independent predictors of increasing AIx, with an odds ratio of 2.09 (P = .02) for the latter.

"The strengths of this study are its longitudinal design and a representative cohort reflecting a range of disease activity," Dr. Berg observed. "Limitations are the low number of patients and that there might be a selection bias when inviting patients to examinations." Traditional risk factors were also not recorded during the 2003 assessment, so the effect of these variables could not be evaluated.

What these data show, however, are that inflammation signaled by elevated CRP and high disease activity measured by ASDAS predict future arterial stiffness, indicating that both are risk factors of CVD in AS. As such, better control of both of these parameters might be a way to reduce risk for CVD in this patient population.

Dr. Berg did not have any conflicts of interest to disclose.

MADRID – High baseline disease activity and serum C-reactive protein levels may be a means of predicting which patients with spondyloarthropathy are likely to develop cardiovascular disease.

Both were linked to arterial stiffness, a surrogate marker for heart disease, in a 5-year follow-up study of 103 hospital-recruited patients with ankylosing spondylitis (Ann. Rheum. Dis 2013;72[Suppls3]:125).

"Reducing disease activity may [therefore] be a viable way of reducing excess cardiovascular disease [CVD] in ankylosing spondylitis [AS]," study investigator Dr. Inger Jorid Berg said at the annual European Congress of Rheumatology.

Baseline disease severity was measured with the ankylosing spondylitis disease activity score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). However, only ASDAS predicted the development of increased arterial stiffness from high baseline disease activity.

"Several studies have shown that patients with ankylosing spondylitis have [an] increased [risk] of cardiovascular disease," noted Dr. Berg, a consultant rheumatologist at Diakonhjemmet Hospital in Oslo. This includes atherosclerotic CVD, she observed, which previous research has linked to having a high ASDAS.

The present investigation explored whether high baseline ASDAS could be used to predict increased arterial stiffness as measured with the Augmentation Index (AIx). The investigators measured arterial stiffness using the SphygmoCor apparatus, a noninvasive system that involves placement of a probe at the radial artery.

Patients included in the study had AS confirmed via modified New York criteria and had undergone assessments in 2003 and again in 2008-2009. The assessments included clinical examinations and questionnaires to assess baseline disease severity and blood tests to measure C-reactive protein (CRP) levels and the erythrocyte sedimentation rate (ESR).

At the baseline assessment in 2003, the patients (56% men) had a mean age of 48 years, and a mean body mass index of 24.4 kg/m². A quarter of the patients were smokers. Their mean ASDAS was 2.5 and their mean BASDAI was 4.1, indicating moderate disease activity. There were only a few known cardiovascular comorbidities present, which included hypertension (5%) and diabetes (3%), although there were more patients with comorbidities at the later assessment. Most (83%) patients were taking nonsteroidal antiinflammatory drugs. Another 17% were using disease-modifying antirheumatic drugs, and very few (2%) were using tumor necrosis factor inhibitors.

"There was a clear trend in increasing CRP values, ESR values, and ASDAS," Dr. Berg said. This was significant for CRP (P = .004) and ASDAS (P = .01), and borderline significant for ESR (P = .05).

Multivariate analysis showed that CRP and ASDAS were independent predictors of increasing AIx, with an odds ratio of 2.09 (P = .02) for the latter.

"The strengths of this study are its longitudinal design and a representative cohort reflecting a range of disease activity," Dr. Berg observed. "Limitations are the low number of patients and that there might be a selection bias when inviting patients to examinations." Traditional risk factors were also not recorded during the 2003 assessment, so the effect of these variables could not be evaluated.

What these data show, however, are that inflammation signaled by elevated CRP and high disease activity measured by ASDAS predict future arterial stiffness, indicating that both are risk factors of CVD in AS. As such, better control of both of these parameters might be a way to reduce risk for CVD in this patient population.

Dr. Berg did not have any conflicts of interest to disclose.

MADRID – High baseline disease activity and serum C-reactive protein levels may be a means of predicting which patients with spondyloarthropathy are likely to develop cardiovascular disease.

Both were linked to arterial stiffness, a surrogate marker for heart disease, in a 5-year follow-up study of 103 hospital-recruited patients with ankylosing spondylitis (Ann. Rheum. Dis 2013;72[Suppls3]:125).

"Reducing disease activity may [therefore] be a viable way of reducing excess cardiovascular disease [CVD] in ankylosing spondylitis [AS]," study investigator Dr. Inger Jorid Berg said at the annual European Congress of Rheumatology.

Baseline disease severity was measured with the ankylosing spondylitis disease activity score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). However, only ASDAS predicted the development of increased arterial stiffness from high baseline disease activity.

"Several studies have shown that patients with ankylosing spondylitis have [an] increased [risk] of cardiovascular disease," noted Dr. Berg, a consultant rheumatologist at Diakonhjemmet Hospital in Oslo. This includes atherosclerotic CVD, she observed, which previous research has linked to having a high ASDAS.

The present investigation explored whether high baseline ASDAS could be used to predict increased arterial stiffness as measured with the Augmentation Index (AIx). The investigators measured arterial stiffness using the SphygmoCor apparatus, a noninvasive system that involves placement of a probe at the radial artery.

Patients included in the study had AS confirmed via modified New York criteria and had undergone assessments in 2003 and again in 2008-2009. The assessments included clinical examinations and questionnaires to assess baseline disease severity and blood tests to measure C-reactive protein (CRP) levels and the erythrocyte sedimentation rate (ESR).

At the baseline assessment in 2003, the patients (56% men) had a mean age of 48 years, and a mean body mass index of 24.4 kg/m². A quarter of the patients were smokers. Their mean ASDAS was 2.5 and their mean BASDAI was 4.1, indicating moderate disease activity. There were only a few known cardiovascular comorbidities present, which included hypertension (5%) and diabetes (3%), although there were more patients with comorbidities at the later assessment. Most (83%) patients were taking nonsteroidal antiinflammatory drugs. Another 17% were using disease-modifying antirheumatic drugs, and very few (2%) were using tumor necrosis factor inhibitors.

"There was a clear trend in increasing CRP values, ESR values, and ASDAS," Dr. Berg said. This was significant for CRP (P = .004) and ASDAS (P = .01), and borderline significant for ESR (P = .05).

Multivariate analysis showed that CRP and ASDAS were independent predictors of increasing AIx, with an odds ratio of 2.09 (P = .02) for the latter.

"The strengths of this study are its longitudinal design and a representative cohort reflecting a range of disease activity," Dr. Berg observed. "Limitations are the low number of patients and that there might be a selection bias when inviting patients to examinations." Traditional risk factors were also not recorded during the 2003 assessment, so the effect of these variables could not be evaluated.

What these data show, however, are that inflammation signaled by elevated CRP and high disease activity measured by ASDAS predict future arterial stiffness, indicating that both are risk factors of CVD in AS. As such, better control of both of these parameters might be a way to reduce risk for CVD in this patient population.

Dr. Berg did not have any conflicts of interest to disclose.

MADRID – Tumor necrosis factor inhibitors are further solidifying their position as the go-to drug class for patients with spondyloarthritis who fail to adequately respond to treatment with nonsteroidal anti-inflammatory drugs.

Results from a series of reports at the annual European Congress of Rheumatology gave further support for the safety and efficacy of tumor necrosis factor (TNF) inhibitors for treating axial spondyloarthritis (SpA), and another report at the meeting provided some of the first evidence for efficacy of the TNF inhibitor class in patients with the less-studied variant, peripheral SpA.

TNF inhibitors "work well for symptoms, and are the gold standard for treating active axial SpA," said Dr. Philip J. Mease, a rheumatologist at Swedish Medical Center in Seattle. He reported evidence for the efficacy of a TNF inhibitor in patients with peripheral SpA without psoriatic involvement, a form of SpA that he said is increasingly being diagnosed after it was first defined a few years ago. The study that Dr. Mease reported on was the first to use the diagnostic criteria for peripheral SpA published by the Assessment of Spondyloarthritis International Society (ASAS) in 2011 (Ann. Rheum. Dis. 2011;70:25-31). Although several TNF inhibitors now have labeling for treating axial SpA and psoriatic arthritis, none currently have U.S. approval for treating peripheral SpA.

The ABILITY-2 (Study of Adalimumab in Subjects With Peripheral Spondyloarthritis) study enrolled patients in the United States, Canada, and several European countries. Patients either had an inadequate response to at least two different nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant of or had contraindications for these drugs. Study participants received either 40 mg of adalimumab (Humira) subcutaneously every other week or placebo for 12 weeks.

The study’s primary endpoint was the percentage of patients achieving the peripheral SpA response criteria 40 at 12 weeks, a composite endpoint that requires at least a 40% improvement on each of three measures: patient global assessment of disease activity; patient global assessment of disease pain; and swollen and tender joint count, enthesitis count, or dactylitis count.

The rate of patients fulfilling the primary endpoint was 39% in 84 patients treated with adalimumab and 20% in 81 patients on placebo, a significant difference. Treatment with adalimumab also was linked to "substantial" and statistically significant improvements after 12 weeks in physical function, health-related quality of life, and work productivity, Dr. Mease reported.

Reports on using TNF inhibitors to treat axial SpA at the congress included results from the first randomized, controlled, phase III trial of a TNF inhibitor to enroll patients from the full range of axial SpA, including roughly equal numbers of patients with ankylosing spondylitis and patients diagnosed with axial SpA but without radiographic changes. The phase III RAPID-axSpA (Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects with Active Axial Spondyloarthritis) trial included 325 patients enrolled at 104 sites in the United States and several other countries. The study enrolled patients who had an elevated blood level of C-reactive protein, evidence of sacroiliitis on an MRI scan, or both, and had failed to adequately respond to treatment with at least one NSAID.

Researchers randomized patients to receive either 200 mg of certolizumab pegol (Cimzia) subcutaneously every 2 weeks, 400 mg of certolizumab pegol subcutaneously every 4 weeks, or placebo. All patients randomized to receive certolizumab pegol began with three subcutaneous loading doses of 400 mg administered at the study’s start and after 2 and 4 weeks. Currently, certolizumab pegol has no labeling for treating patients with axial SpA, unlike several other TNF inhibitors such as adalimumab and etanercept (Enbrel).

The study’s primary endpoint was the percentage of patients achieving an ASAS 20 response after 12 weeks of treatment, which requires at least a 20% improvement in at least three of these four criteria: patient global assessment, spinal pain assessment, function, and inflammation. This endpoint was reached by 38% of the 107 placebo patients, 58% of the 111 patients who received certolizumab pegol every 2 weeks, and 64% of those who received certolizumab pegol every 4 weeks, showing statistically significant differences in favor of the active treatment, reported Dr. Robert B.M. Landewé at the congress.

Response rates were similar among the patients with ankylosing spondylitis and those with no radiographic pathology. After 24 weeks of treatment, the rate of ASAS 20 responders fell to 29% of the placebo patients, compared with increases to 67% of patients receiving certolizumab pegol every 2 weeks and to 70% in those getting the drug every 4 weeks.

Dr. Landewé, who is a professor of rheumatology at the Academic Medical Center in Amsterdam, also presented results for several other secondary measures of response. One of these, the Ankylosing Spondylitis Disease Activity Score (ASDAS), showed that inactive disease developed after 24 weeks of treatment in 4% of the placebo-treated patients, 30% of the patients who received certolizumab pegol every 2 weeks, and 31% of patients who received the drug every 4 weeks. The results also showed no new signals of adverse effects, compared with several prior pivotal trials of certolizumab pegol.

Another set of measures in the same study focused on the impact of 24 weeks of treatment on work and household productivity and participation in social activities. Among the 69% of patients in the study who were employed, treatment with either dosage of certolizumab pegol was associated with an average of 10 more productive days of paid work per patient, compared with placebo, reported Dr. Désirée van der Heijde, professor of rheumatology at Leiden University in the Netherlands. During the 24 weeks of treatment, the active regimens also resulted in an added 13-17 days of productive household work and an average of about 10 added days of social or leisure activities, compared with placebo-treated patients.

Results from a third study reported at the meeting included outcomes from patients with axial SpA and objective evidence of inflammation at entry who remained on treatment with adalimumab during 2 years of follow-up in the ABILITY-1 study. This trial’s primary-endpoint results, which were recently published (Ann. Rheum. Dis. 2013;72:815-22), showed that 40 mg of adalimumab administered every other week was significantly better than placebo for reducing disease activity after 12 weeks of treatment. The new results came from 107 patients who remained in the study and received 104 weeks of adalimumab treatment.

After 2 years, 66% of patients showed ASAS 40 responses, and 44% had inactive disease based on their ASDAS, reported Dr. Joachim Sieper, professor and chief of rheumatology at Charité University Hospital in Berlin. Most of the patients in remission at 104 weeks had also been in remission after 52 and 80 weeks of treatment. In addition, the 2-year data showed no new safety concerns, compared with several other prior reports of long-term treatment with adalimumab, he said.

The ABILITY-1 and ABILITY-2 trials were sponsored by AbbVie, which markets adalimumab. Dr. Mease has been a consultant to and has received research support from AbbVie and other companies. Dr. Sieper has been a consultant to and has received research support from Abbott (from which AbbVie was created) as well as Merck, Pfizer, and UCB. The RAPID-axSpA trial was sponsored by UCB, which markets certolizumab. Dr. Landewé has been a consultant to and has received research support from UCB and other companies. Dr. van der Heijde has been a consultant to and has received grant support from UCB and other companies.

[email protected]

On Twitter @mitchelzoler

MADRID – Tumor necrosis factor inhibitors are further solidifying their position as the go-to drug class for patients with spondyloarthritis who fail to adequately respond to treatment with nonsteroidal anti-inflammatory drugs.

Results from a series of reports at the annual European Congress of Rheumatology gave further support for the safety and efficacy of tumor necrosis factor (TNF) inhibitors for treating axial spondyloarthritis (SpA), and another report at the meeting provided some of the first evidence for efficacy of the TNF inhibitor class in patients with the less-studied variant, peripheral SpA.

TNF inhibitors "work well for symptoms, and are the gold standard for treating active axial SpA," said Dr. Philip J. Mease, a rheumatologist at Swedish Medical Center in Seattle. He reported evidence for the efficacy of a TNF inhibitor in patients with peripheral SpA without psoriatic involvement, a form of SpA that he said is increasingly being diagnosed after it was first defined a few years ago. The study that Dr. Mease reported on was the first to use the diagnostic criteria for peripheral SpA published by the Assessment of Spondyloarthritis International Society (ASAS) in 2011 (Ann. Rheum. Dis. 2011;70:25-31). Although several TNF inhibitors now have labeling for treating axial SpA and psoriatic arthritis, none currently have U.S. approval for treating peripheral SpA.

The ABILITY-2 (Study of Adalimumab in Subjects With Peripheral Spondyloarthritis) study enrolled patients in the United States, Canada, and several European countries. Patients either had an inadequate response to at least two different nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant of or had contraindications for these drugs. Study participants received either 40 mg of adalimumab (Humira) subcutaneously every other week or placebo for 12 weeks.

The study’s primary endpoint was the percentage of patients achieving the peripheral SpA response criteria 40 at 12 weeks, a composite endpoint that requires at least a 40% improvement on each of three measures: patient global assessment of disease activity; patient global assessment of disease pain; and swollen and tender joint count, enthesitis count, or dactylitis count.

The rate of patients fulfilling the primary endpoint was 39% in 84 patients treated with adalimumab and 20% in 81 patients on placebo, a significant difference. Treatment with adalimumab also was linked to "substantial" and statistically significant improvements after 12 weeks in physical function, health-related quality of life, and work productivity, Dr. Mease reported.

Reports on using TNF inhibitors to treat axial SpA at the congress included results from the first randomized, controlled, phase III trial of a TNF inhibitor to enroll patients from the full range of axial SpA, including roughly equal numbers of patients with ankylosing spondylitis and patients diagnosed with axial SpA but without radiographic changes. The phase III RAPID-axSpA (Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects with Active Axial Spondyloarthritis) trial included 325 patients enrolled at 104 sites in the United States and several other countries. The study enrolled patients who had an elevated blood level of C-reactive protein, evidence of sacroiliitis on an MRI scan, or both, and had failed to adequately respond to treatment with at least one NSAID.

Researchers randomized patients to receive either 200 mg of certolizumab pegol (Cimzia) subcutaneously every 2 weeks, 400 mg of certolizumab pegol subcutaneously every 4 weeks, or placebo. All patients randomized to receive certolizumab pegol began with three subcutaneous loading doses of 400 mg administered at the study’s start and after 2 and 4 weeks. Currently, certolizumab pegol has no labeling for treating patients with axial SpA, unlike several other TNF inhibitors such as adalimumab and etanercept (Enbrel).

The study’s primary endpoint was the percentage of patients achieving an ASAS 20 response after 12 weeks of treatment, which requires at least a 20% improvement in at least three of these four criteria: patient global assessment, spinal pain assessment, function, and inflammation. This endpoint was reached by 38% of the 107 placebo patients, 58% of the 111 patients who received certolizumab pegol every 2 weeks, and 64% of those who received certolizumab pegol every 4 weeks, showing statistically significant differences in favor of the active treatment, reported Dr. Robert B.M. Landewé at the congress.

Response rates were similar among the patients with ankylosing spondylitis and those with no radiographic pathology. After 24 weeks of treatment, the rate of ASAS 20 responders fell to 29% of the placebo patients, compared with increases to 67% of patients receiving certolizumab pegol every 2 weeks and to 70% in those getting the drug every 4 weeks.

Dr. Landewé, who is a professor of rheumatology at the Academic Medical Center in Amsterdam, also presented results for several other secondary measures of response. One of these, the Ankylosing Spondylitis Disease Activity Score (ASDAS), showed that inactive disease developed after 24 weeks of treatment in 4% of the placebo-treated patients, 30% of the patients who received certolizumab pegol every 2 weeks, and 31% of patients who received the drug every 4 weeks. The results also showed no new signals of adverse effects, compared with several prior pivotal trials of certolizumab pegol.

Another set of measures in the same study focused on the impact of 24 weeks of treatment on work and household productivity and participation in social activities. Among the 69% of patients in the study who were employed, treatment with either dosage of certolizumab pegol was associated with an average of 10 more productive days of paid work per patient, compared with placebo, reported Dr. Désirée van der Heijde, professor of rheumatology at Leiden University in the Netherlands. During the 24 weeks of treatment, the active regimens also resulted in an added 13-17 days of productive household work and an average of about 10 added days of social or leisure activities, compared with placebo-treated patients.

Results from a third study reported at the meeting included outcomes from patients with axial SpA and objective evidence of inflammation at entry who remained on treatment with adalimumab during 2 years of follow-up in the ABILITY-1 study. This trial’s primary-endpoint results, which were recently published (Ann. Rheum. Dis. 2013;72:815-22), showed that 40 mg of adalimumab administered every other week was significantly better than placebo for reducing disease activity after 12 weeks of treatment. The new results came from 107 patients who remained in the study and received 104 weeks of adalimumab treatment.

After 2 years, 66% of patients showed ASAS 40 responses, and 44% had inactive disease based on their ASDAS, reported Dr. Joachim Sieper, professor and chief of rheumatology at Charité University Hospital in Berlin. Most of the patients in remission at 104 weeks had also been in remission after 52 and 80 weeks of treatment. In addition, the 2-year data showed no new safety concerns, compared with several other prior reports of long-term treatment with adalimumab, he said.

The ABILITY-1 and ABILITY-2 trials were sponsored by AbbVie, which markets adalimumab. Dr. Mease has been a consultant to and has received research support from AbbVie and other companies. Dr. Sieper has been a consultant to and has received research support from Abbott (from which AbbVie was created) as well as Merck, Pfizer, and UCB. The RAPID-axSpA trial was sponsored by UCB, which markets certolizumab. Dr. Landewé has been a consultant to and has received research support from UCB and other companies. Dr. van der Heijde has been a consultant to and has received grant support from UCB and other companies.

[email protected]

On Twitter @mitchelzoler

MADRID – Tumor necrosis factor inhibitors are further solidifying their position as the go-to drug class for patients with spondyloarthritis who fail to adequately respond to treatment with nonsteroidal anti-inflammatory drugs.

Results from a series of reports at the annual European Congress of Rheumatology gave further support for the safety and efficacy of tumor necrosis factor (TNF) inhibitors for treating axial spondyloarthritis (SpA), and another report at the meeting provided some of the first evidence for efficacy of the TNF inhibitor class in patients with the less-studied variant, peripheral SpA.

TNF inhibitors "work well for symptoms, and are the gold standard for treating active axial SpA," said Dr. Philip J. Mease, a rheumatologist at Swedish Medical Center in Seattle. He reported evidence for the efficacy of a TNF inhibitor in patients with peripheral SpA without psoriatic involvement, a form of SpA that he said is increasingly being diagnosed after it was first defined a few years ago. The study that Dr. Mease reported on was the first to use the diagnostic criteria for peripheral SpA published by the Assessment of Spondyloarthritis International Society (ASAS) in 2011 (Ann. Rheum. Dis. 2011;70:25-31). Although several TNF inhibitors now have labeling for treating axial SpA and psoriatic arthritis, none currently have U.S. approval for treating peripheral SpA.

The ABILITY-2 (Study of Adalimumab in Subjects With Peripheral Spondyloarthritis) study enrolled patients in the United States, Canada, and several European countries. Patients either had an inadequate response to at least two different nonsteroidal anti-inflammatory drugs (NSAIDs) or were intolerant of or had contraindications for these drugs. Study participants received either 40 mg of adalimumab (Humira) subcutaneously every other week or placebo for 12 weeks.

The study’s primary endpoint was the percentage of patients achieving the peripheral SpA response criteria 40 at 12 weeks, a composite endpoint that requires at least a 40% improvement on each of three measures: patient global assessment of disease activity; patient global assessment of disease pain; and swollen and tender joint count, enthesitis count, or dactylitis count.

The rate of patients fulfilling the primary endpoint was 39% in 84 patients treated with adalimumab and 20% in 81 patients on placebo, a significant difference. Treatment with adalimumab also was linked to "substantial" and statistically significant improvements after 12 weeks in physical function, health-related quality of life, and work productivity, Dr. Mease reported.

Reports on using TNF inhibitors to treat axial SpA at the congress included results from the first randomized, controlled, phase III trial of a TNF inhibitor to enroll patients from the full range of axial SpA, including roughly equal numbers of patients with ankylosing spondylitis and patients diagnosed with axial SpA but without radiographic changes. The phase III RAPID-axSpA (Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects with Active Axial Spondyloarthritis) trial included 325 patients enrolled at 104 sites in the United States and several other countries. The study enrolled patients who had an elevated blood level of C-reactive protein, evidence of sacroiliitis on an MRI scan, or both, and had failed to adequately respond to treatment with at least one NSAID.

Researchers randomized patients to receive either 200 mg of certolizumab pegol (Cimzia) subcutaneously every 2 weeks, 400 mg of certolizumab pegol subcutaneously every 4 weeks, or placebo. All patients randomized to receive certolizumab pegol began with three subcutaneous loading doses of 400 mg administered at the study’s start and after 2 and 4 weeks. Currently, certolizumab pegol has no labeling for treating patients with axial SpA, unlike several other TNF inhibitors such as adalimumab and etanercept (Enbrel).

The study’s primary endpoint was the percentage of patients achieving an ASAS 20 response after 12 weeks of treatment, which requires at least a 20% improvement in at least three of these four criteria: patient global assessment, spinal pain assessment, function, and inflammation. This endpoint was reached by 38% of the 107 placebo patients, 58% of the 111 patients who received certolizumab pegol every 2 weeks, and 64% of those who received certolizumab pegol every 4 weeks, showing statistically significant differences in favor of the active treatment, reported Dr. Robert B.M. Landewé at the congress.

Response rates were similar among the patients with ankylosing spondylitis and those with no radiographic pathology. After 24 weeks of treatment, the rate of ASAS 20 responders fell to 29% of the placebo patients, compared with increases to 67% of patients receiving certolizumab pegol every 2 weeks and to 70% in those getting the drug every 4 weeks.

Dr. Landewé, who is a professor of rheumatology at the Academic Medical Center in Amsterdam, also presented results for several other secondary measures of response. One of these, the Ankylosing Spondylitis Disease Activity Score (ASDAS), showed that inactive disease developed after 24 weeks of treatment in 4% of the placebo-treated patients, 30% of the patients who received certolizumab pegol every 2 weeks, and 31% of patients who received the drug every 4 weeks. The results also showed no new signals of adverse effects, compared with several prior pivotal trials of certolizumab pegol.

Another set of measures in the same study focused on the impact of 24 weeks of treatment on work and household productivity and participation in social activities. Among the 69% of patients in the study who were employed, treatment with either dosage of certolizumab pegol was associated with an average of 10 more productive days of paid work per patient, compared with placebo, reported Dr. Désirée van der Heijde, professor of rheumatology at Leiden University in the Netherlands. During the 24 weeks of treatment, the active regimens also resulted in an added 13-17 days of productive household work and an average of about 10 added days of social or leisure activities, compared with placebo-treated patients.

Results from a third study reported at the meeting included outcomes from patients with axial SpA and objective evidence of inflammation at entry who remained on treatment with adalimumab during 2 years of follow-up in the ABILITY-1 study. This trial’s primary-endpoint results, which were recently published (Ann. Rheum. Dis. 2013;72:815-22), showed that 40 mg of adalimumab administered every other week was significantly better than placebo for reducing disease activity after 12 weeks of treatment. The new results came from 107 patients who remained in the study and received 104 weeks of adalimumab treatment.

After 2 years, 66% of patients showed ASAS 40 responses, and 44% had inactive disease based on their ASDAS, reported Dr. Joachim Sieper, professor and chief of rheumatology at Charité University Hospital in Berlin. Most of the patients in remission at 104 weeks had also been in remission after 52 and 80 weeks of treatment. In addition, the 2-year data showed no new safety concerns, compared with several other prior reports of long-term treatment with adalimumab, he said.

The ABILITY-1 and ABILITY-2 trials were sponsored by AbbVie, which markets adalimumab. Dr. Mease has been a consultant to and has received research support from AbbVie and other companies. Dr. Sieper has been a consultant to and has received research support from Abbott (from which AbbVie was created) as well as Merck, Pfizer, and UCB. The RAPID-axSpA trial was sponsored by UCB, which markets certolizumab. Dr. Landewé has been a consultant to and has received research support from UCB and other companies. Dr. van der Heijde has been a consultant to and has received grant support from UCB and other companies.

[email protected]

On Twitter @mitchelzoler

Spondyloarthritis became, in 2009, a much better defined disease, and partly as a result it is something that physicians increasingly see the more they look for it. That’s especially true for peripheral spondyloarthritis, historically ill defined and rarely diagnosed.

The prevalence of recognized cases of peripheral spondyloarthritis (SpA) and its more common sister disease axial SpA began rising when the Assessment of Spondyloarthritis International Society released new criteria in 2009 for diagnosing both axial and peripheral SpA. The consequence of the new peripheral SpA definitions has been increased diagnostic awareness over the ensuing 4 years.

Courtesy Gray's Anatomy/Bartleby.com.com

"The nonaxial, nonpsoriatic peripheral SpA population is unique, and we increasingly find these patients as we have started to look for them," Seattle rheumatologist Dr. Philip Mease told me in June at the annual European Congress of Rheumatology in Madrid.

These patients often are initially misdiagnosed and unrecognized as peripheral SpA cases with presumed "fibromyalgia or nonspecific aches and pains" under the care of an orthopedist, physiatrist, or primary care physician. But more recently such patients "are starting to surface with evidence of elevated CRP [C-reactive protein] and inflammatory symptoms," including morning stiffness, back pain, and symptoms at the peripheral entheses that start at a relatively young age. Dr. Mease suggested that these "entry point" clinicians be on the lookout for "puzzlingly persistent pain in peripheral joint or tendon-insertion sites," along with subtle clues like an old episode of uveitis or a family history of psoriasis, all signals of a possible case of peripheral SpA. On further examination, patients with symptoms such as persistent Achilles tendonitis show elevated CRP levels, and an "MRI scan that lights up where the Achilles tendon inserts."

Dr. Mease told me that he sees growing awareness among primary care clinicians in the community about these symptoms and the fact that they flag an inflammatory, rheumatologic process that’s best managed by anti-inflammatory treatments, such as tumor necrosis factor inhibitors and newer drugs now receiving approval for rheumatic diseases.

"There is such a rising tide of interest in SpA in general," he said, a tide traceable back to the landmark definitions of 2009.

–By Mitchel L. Zoler

[email protected]

On Twitter @mitchelzoler

Spondyloarthritis became, in 2009, a much better defined disease, and partly as a result it is something that physicians increasingly see the more they look for it. That’s especially true for peripheral spondyloarthritis, historically ill defined and rarely diagnosed.

The prevalence of recognized cases of peripheral spondyloarthritis (SpA) and its more common sister disease axial SpA began rising when the Assessment of Spondyloarthritis International Society released new criteria in 2009 for diagnosing both axial and peripheral SpA. The consequence of the new peripheral SpA definitions has been increased diagnostic awareness over the ensuing 4 years.

Courtesy Gray's Anatomy/Bartleby.com.com

"The nonaxial, nonpsoriatic peripheral SpA population is unique, and we increasingly find these patients as we have started to look for them," Seattle rheumatologist Dr. Philip Mease told me in June at the annual European Congress of Rheumatology in Madrid.

These patients often are initially misdiagnosed and unrecognized as peripheral SpA cases with presumed "fibromyalgia or nonspecific aches and pains" under the care of an orthopedist, physiatrist, or primary care physician. But more recently such patients "are starting to surface with evidence of elevated CRP [C-reactive protein] and inflammatory symptoms," including morning stiffness, back pain, and symptoms at the peripheral entheses that start at a relatively young age. Dr. Mease suggested that these "entry point" clinicians be on the lookout for "puzzlingly persistent pain in peripheral joint or tendon-insertion sites," along with subtle clues like an old episode of uveitis or a family history of psoriasis, all signals of a possible case of peripheral SpA. On further examination, patients with symptoms such as persistent Achilles tendonitis show elevated CRP levels, and an "MRI scan that lights up where the Achilles tendon inserts."

Dr. Mease told me that he sees growing awareness among primary care clinicians in the community about these symptoms and the fact that they flag an inflammatory, rheumatologic process that’s best managed by anti-inflammatory treatments, such as tumor necrosis factor inhibitors and newer drugs now receiving approval for rheumatic diseases.

"There is such a rising tide of interest in SpA in general," he said, a tide traceable back to the landmark definitions of 2009.

–By Mitchel L. Zoler

[email protected]

On Twitter @mitchelzoler

Spondyloarthritis became, in 2009, a much better defined disease, and partly as a result it is something that physicians increasingly see the more they look for it. That’s especially true for peripheral spondyloarthritis, historically ill defined and rarely diagnosed.

The prevalence of recognized cases of peripheral spondyloarthritis (SpA) and its more common sister disease axial SpA began rising when the Assessment of Spondyloarthritis International Society released new criteria in 2009 for diagnosing both axial and peripheral SpA. The consequence of the new peripheral SpA definitions has been increased diagnostic awareness over the ensuing 4 years.

Courtesy Gray's Anatomy/Bartleby.com.com

"The nonaxial, nonpsoriatic peripheral SpA population is unique, and we increasingly find these patients as we have started to look for them," Seattle rheumatologist Dr. Philip Mease told me in June at the annual European Congress of Rheumatology in Madrid.

These patients often are initially misdiagnosed and unrecognized as peripheral SpA cases with presumed "fibromyalgia or nonspecific aches and pains" under the care of an orthopedist, physiatrist, or primary care physician. But more recently such patients "are starting to surface with evidence of elevated CRP [C-reactive protein] and inflammatory symptoms," including morning stiffness, back pain, and symptoms at the peripheral entheses that start at a relatively young age. Dr. Mease suggested that these "entry point" clinicians be on the lookout for "puzzlingly persistent pain in peripheral joint or tendon-insertion sites," along with subtle clues like an old episode of uveitis or a family history of psoriasis, all signals of a possible case of peripheral SpA. On further examination, patients with symptoms such as persistent Achilles tendonitis show elevated CRP levels, and an "MRI scan that lights up where the Achilles tendon inserts."

Dr. Mease told me that he sees growing awareness among primary care clinicians in the community about these symptoms and the fact that they flag an inflammatory, rheumatologic process that’s best managed by anti-inflammatory treatments, such as tumor necrosis factor inhibitors and newer drugs now receiving approval for rheumatic diseases.

"There is such a rising tide of interest in SpA in general," he said, a tide traceable back to the landmark definitions of 2009.

–By Mitchel L. Zoler

[email protected]

On Twitter @mitchelzoler

Patients with ankylosing spondylitis who participated in a progressive muscle strengthening program gained significant improvements in muscle strength and walking performance after 4 months, compared with those who did not participate, Dr. Fabio Jennings reported at the annual European Congress of Rheumatology.

The exercise program, which involved resistance training with the Swiss ball, was also well tolerated and was not associated with negative effects on disease activity, said Dr. Jennings of the rheumatology division at the Federal University of Sao Paulo, Brazil.

Dr. Jennings and his colleagues performed a randomized, controlled, single-blind, prospective trial of 60 patients with ankylosing spondylitis (AS).

Exercise is recommended for people with AS, but the benefits of a specific exercise program have not been well defined, Dr. Jennings noted.

In the study, 30 patients were randomized to the supervised exercise program, which entailed eight resistance exercises using free weights on a Swiss ball twice a week for 16 weeks, with increases in load every 4 weeks. The 30 patients in the control group continued regular treatment with medications, with no exercise. Demographics, clinical features, and medications were similar in the two groups at baseline.

The impact of the exercise on functional capacity, quality of life, muscle strength, and mobility was evaluated using the BASFI (Bath Ankylosing Spondylitis Functional Index), HAQ-S (Health Assessment Questionnaire for Spondyloarthropathies), the 6-minute walk test, and other assessment tools, every 4 weeks. Disease activity was measured with the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), erythrocyte sedimentation rate (ESR), and C-reactive protein levels.

After 4 months, there were statistically significant differences between the two groups in the strengths of the muscles used in performing the exercises (abdominal, squat, triceps, reverse fly, and rowing exercises), favoring the intervention group. These patients also had significant improvements in the 6-minute walk test; and they were satisfied with the treatment, as reflected by significant differences between the two groups in the Likert scale used to assess patient satisfaction at all time points measured.

In addition, disease activity – as measured by BASDAI, ESR, and C-reactive protein – did not worsen among those who participated in the exercise program.

The study showed that this type of exercise program, using a Swiss ball to improve muscle strength, "is a beneficial and safe intervention" in people with AS, lead author Mr. Marcelo Cardoso de Souza, a physiotherapist and member of a multidisciplinary rehabilitation team at the university, said in an interview. For these patients, improvement in muscular performance and functional capacity is important, he said, noting that before clinicians refer patients to such a program, patients should undergo a medical evaluation, and the program should be provided by an experienced professional.

None of the investigators had relevant financial conflicts of interest.

[email protected]

Patients with ankylosing spondylitis who participated in a progressive muscle strengthening program gained significant improvements in muscle strength and walking performance after 4 months, compared with those who did not participate, Dr. Fabio Jennings reported at the annual European Congress of Rheumatology.

The exercise program, which involved resistance training with the Swiss ball, was also well tolerated and was not associated with negative effects on disease activity, said Dr. Jennings of the rheumatology division at the Federal University of Sao Paulo, Brazil.

Dr. Jennings and his colleagues performed a randomized, controlled, single-blind, prospective trial of 60 patients with ankylosing spondylitis (AS).

Exercise is recommended for people with AS, but the benefits of a specific exercise program have not been well defined, Dr. Jennings noted.

In the study, 30 patients were randomized to the supervised exercise program, which entailed eight resistance exercises using free weights on a Swiss ball twice a week for 16 weeks, with increases in load every 4 weeks. The 30 patients in the control group continued regular treatment with medications, with no exercise. Demographics, clinical features, and medications were similar in the two groups at baseline.

The impact of the exercise on functional capacity, quality of life, muscle strength, and mobility was evaluated using the BASFI (Bath Ankylosing Spondylitis Functional Index), HAQ-S (Health Assessment Questionnaire for Spondyloarthropathies), the 6-minute walk test, and other assessment tools, every 4 weeks. Disease activity was measured with the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), erythrocyte sedimentation rate (ESR), and C-reactive protein levels.

After 4 months, there were statistically significant differences between the two groups in the strengths of the muscles used in performing the exercises (abdominal, squat, triceps, reverse fly, and rowing exercises), favoring the intervention group. These patients also had significant improvements in the 6-minute walk test; and they were satisfied with the treatment, as reflected by significant differences between the two groups in the Likert scale used to assess patient satisfaction at all time points measured.

In addition, disease activity – as measured by BASDAI, ESR, and C-reactive protein – did not worsen among those who participated in the exercise program.

The study showed that this type of exercise program, using a Swiss ball to improve muscle strength, "is a beneficial and safe intervention" in people with AS, lead author Mr. Marcelo Cardoso de Souza, a physiotherapist and member of a multidisciplinary rehabilitation team at the university, said in an interview. For these patients, improvement in muscular performance and functional capacity is important, he said, noting that before clinicians refer patients to such a program, patients should undergo a medical evaluation, and the program should be provided by an experienced professional.

None of the investigators had relevant financial conflicts of interest.

[email protected]

Patients with ankylosing spondylitis who participated in a progressive muscle strengthening program gained significant improvements in muscle strength and walking performance after 4 months, compared with those who did not participate, Dr. Fabio Jennings reported at the annual European Congress of Rheumatology.

The exercise program, which involved resistance training with the Swiss ball, was also well tolerated and was not associated with negative effects on disease activity, said Dr. Jennings of the rheumatology division at the Federal University of Sao Paulo, Brazil.

Dr. Jennings and his colleagues performed a randomized, controlled, single-blind, prospective trial of 60 patients with ankylosing spondylitis (AS).

Exercise is recommended for people with AS, but the benefits of a specific exercise program have not been well defined, Dr. Jennings noted.

In the study, 30 patients were randomized to the supervised exercise program, which entailed eight resistance exercises using free weights on a Swiss ball twice a week for 16 weeks, with increases in load every 4 weeks. The 30 patients in the control group continued regular treatment with medications, with no exercise. Demographics, clinical features, and medications were similar in the two groups at baseline.

The impact of the exercise on functional capacity, quality of life, muscle strength, and mobility was evaluated using the BASFI (Bath Ankylosing Spondylitis Functional Index), HAQ-S (Health Assessment Questionnaire for Spondyloarthropathies), the 6-minute walk test, and other assessment tools, every 4 weeks. Disease activity was measured with the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), erythrocyte sedimentation rate (ESR), and C-reactive protein levels.

After 4 months, there were statistically significant differences between the two groups in the strengths of the muscles used in performing the exercises (abdominal, squat, triceps, reverse fly, and rowing exercises), favoring the intervention group. These patients also had significant improvements in the 6-minute walk test; and they were satisfied with the treatment, as reflected by significant differences between the two groups in the Likert scale used to assess patient satisfaction at all time points measured.

In addition, disease activity – as measured by BASDAI, ESR, and C-reactive protein – did not worsen among those who participated in the exercise program.

The study showed that this type of exercise program, using a Swiss ball to improve muscle strength, "is a beneficial and safe intervention" in people with AS, lead author Mr. Marcelo Cardoso de Souza, a physiotherapist and member of a multidisciplinary rehabilitation team at the university, said in an interview. For these patients, improvement in muscular performance and functional capacity is important, he said, noting that before clinicians refer patients to such a program, patients should undergo a medical evaluation, and the program should be provided by an experienced professional.

None of the investigators had relevant financial conflicts of interest.

[email protected]