American College of Rheumatology (ACR): State-of-the-Art Clinical Symposium

CHICAGO – A number of questions remain regarding the safety and efficacy of rituximab for severe antineutrophil cytoplasmic antibody–associated vasculitis, according to Dr. Phillip Seo.

For example, it remains unclear how the sickest patients – such as those with ANCA-associated vasculitis (AAV), plus renal or respiratory failure – should be managed, and it also remains to be seen what the true effects of the drop in immunoglobulin levels that are seen after several treatment cycles may be, said Dr. Seo said at a symposium sponsored by the American College of Rheumatology.

Rituximab, a chimeric monoclonal antibody against the protein CD20 that is primarily found on the surface of B cells, was first approved in the United States in 2006 for use in combination with methotrexate for adult rheumatoid arthritis patients who failed to respond adequately to TNF (tumor necrosis factor)–antagonist therapies. On April 19, it received a new U.S. Food and Drug Administration approval for use – along with a corticosteroid – in the treatment of Wegener’s granulomatosis and microscopic polyangiitis.

The new approval for these indications was based on findings from the 6-month remission-induction phase of the randomized, double-blind, multicenter, active-controlled RAVE (Rituximab in ANCA-Associated Vasculitis) trial. The RAVE findings demonstrated that rituximab is not inferior to cyclophosphamide for remission induction at 6 months in patients with these severe forms of ANCA-associated vasculitis. Data from an 18-month maintenance phase have not yet been published.

The remission-induction data are of particular interest for patients who fail to respond to cyclophosphamide, or who aren’t candidates for treatment with the cytotoxic agent, which has been the cornerstone of therapy in these diseases. In very young patients, for example, there may be concerns about future fertility that would preclude the use of cyclophosphamide. In the elderly, there may be concerns about bone marrow suppression, said Dr. Seo, codirector of the vasculitis center at Johns Hopkins University, Baltimore.

Indeed, data from the 1970s from the National Institutes of Health, which established cyclophosphamide as a mainstay of treatment for AAV, showed that about 25% of patients have an incomplete response even after 3-5 years of therapy. Intolerance is also an issue, particularly for those with hemorrhagic cystitis or bone marrow suppression resulting from prior exposures, he said.

The 6-month data from RAVE, which were published in July, provide some hope for such patients; the data showed that outcomes were statistically similar in 197 patients who were randomized to treatment with daily oral prednisone (1 mg/kg per day up to 80 mg/day) and either a "very standard course" of oral cyclophosphamide (2 mg/kg per day for 3-6 months, followed by azathioprine to maintain remission) plus rituximab placebo, or rituximab (375 mg/m² infusions once weekly for 4 weeks) plus cyclophosphamide placebo (N. Engl. J. Med. 2010; 363:221-32), Dr. Seo said.

Not only was rituximab shown to be noninferior to cyclophosphamide for inducing complete remission with steroid taper, but treatment response did not differ significantly by disease type. However, patients with Wegener’s granulomatosis trended toward having a slightly better treatment response, he noted.

Treatment response was, however, significantly better with rituximab among those with severe disease flare at study baseline.

"Those [severe flare] patients do much better when they get rituximab ... and in fact this might highlight an important use for rituximab in the future," he said.

However, because patients with renal or respiratory failure were ineligible for the trial, it remains unclear whether rituximab is a viable option for these patients.

"So, although I think rituximab still might work, there’s not really any data with any of these patients," he said.

Also, long-term treatment may be a concern. Many patients receive multiple courses, and their immunoglobulin levels start to drop after about five cycles of rituximab.

"The data seem to indicate that this doesn’t matter and doesn’t seem to be associated with any increased risk of infection. Yet emotionally, I find that so hard to believe," Dr. Seo said, adding that this "is something I’m going to be watching for in the near future."

A final concern mentioned by Dr. Seo is the risk of progressive multifocal leukoencephalopathy (PML), which used to be a concern mainly in patients with HIV/AIDS or in patients receiving cancer chemotherapy. "Unfortunately we now have to talk about it as well," he said.

The majority of patients with rheumatic illness who develop PML after treatment with rituximab have received multiple courses of immunosuppression leading up to rituximab, and this likely explains the majority of cases, but it doesn’t explain all cases.

"So this is a story that continues to evolve," he said.

Dr. Seo disclosed that he has received consulting fees and other remuneration from Genentech.

CHICAGO – A number of questions remain regarding the safety and efficacy of rituximab for severe antineutrophil cytoplasmic antibody–associated vasculitis, according to Dr. Phillip Seo.

For example, it remains unclear how the sickest patients – such as those with ANCA-associated vasculitis (AAV), plus renal or respiratory failure – should be managed, and it also remains to be seen what the true effects of the drop in immunoglobulin levels that are seen after several treatment cycles may be, said Dr. Seo said at a symposium sponsored by the American College of Rheumatology.

Rituximab, a chimeric monoclonal antibody against the protein CD20 that is primarily found on the surface of B cells, was first approved in the United States in 2006 for use in combination with methotrexate for adult rheumatoid arthritis patients who failed to respond adequately to TNF (tumor necrosis factor)–antagonist therapies. On April 19, it received a new U.S. Food and Drug Administration approval for use – along with a corticosteroid – in the treatment of Wegener’s granulomatosis and microscopic polyangiitis.

The new approval for these indications was based on findings from the 6-month remission-induction phase of the randomized, double-blind, multicenter, active-controlled RAVE (Rituximab in ANCA-Associated Vasculitis) trial. The RAVE findings demonstrated that rituximab is not inferior to cyclophosphamide for remission induction at 6 months in patients with these severe forms of ANCA-associated vasculitis. Data from an 18-month maintenance phase have not yet been published.

The remission-induction data are of particular interest for patients who fail to respond to cyclophosphamide, or who aren’t candidates for treatment with the cytotoxic agent, which has been the cornerstone of therapy in these diseases. In very young patients, for example, there may be concerns about future fertility that would preclude the use of cyclophosphamide. In the elderly, there may be concerns about bone marrow suppression, said Dr. Seo, codirector of the vasculitis center at Johns Hopkins University, Baltimore.

Indeed, data from the 1970s from the National Institutes of Health, which established cyclophosphamide as a mainstay of treatment for AAV, showed that about 25% of patients have an incomplete response even after 3-5 years of therapy. Intolerance is also an issue, particularly for those with hemorrhagic cystitis or bone marrow suppression resulting from prior exposures, he said.

The 6-month data from RAVE, which were published in July, provide some hope for such patients; the data showed that outcomes were statistically similar in 197 patients who were randomized to treatment with daily oral prednisone (1 mg/kg per day up to 80 mg/day) and either a "very standard course" of oral cyclophosphamide (2 mg/kg per day for 3-6 months, followed by azathioprine to maintain remission) plus rituximab placebo, or rituximab (375 mg/m² infusions once weekly for 4 weeks) plus cyclophosphamide placebo (N. Engl. J. Med. 2010; 363:221-32), Dr. Seo said.

Not only was rituximab shown to be noninferior to cyclophosphamide for inducing complete remission with steroid taper, but treatment response did not differ significantly by disease type. However, patients with Wegener’s granulomatosis trended toward having a slightly better treatment response, he noted.

Treatment response was, however, significantly better with rituximab among those with severe disease flare at study baseline.

"Those [severe flare] patients do much better when they get rituximab ... and in fact this might highlight an important use for rituximab in the future," he said.

However, because patients with renal or respiratory failure were ineligible for the trial, it remains unclear whether rituximab is a viable option for these patients.

"So, although I think rituximab still might work, there’s not really any data with any of these patients," he said.

Also, long-term treatment may be a concern. Many patients receive multiple courses, and their immunoglobulin levels start to drop after about five cycles of rituximab.

"The data seem to indicate that this doesn’t matter and doesn’t seem to be associated with any increased risk of infection. Yet emotionally, I find that so hard to believe," Dr. Seo said, adding that this "is something I’m going to be watching for in the near future."

A final concern mentioned by Dr. Seo is the risk of progressive multifocal leukoencephalopathy (PML), which used to be a concern mainly in patients with HIV/AIDS or in patients receiving cancer chemotherapy. "Unfortunately we now have to talk about it as well," he said.

The majority of patients with rheumatic illness who develop PML after treatment with rituximab have received multiple courses of immunosuppression leading up to rituximab, and this likely explains the majority of cases, but it doesn’t explain all cases.

"So this is a story that continues to evolve," he said.

Dr. Seo disclosed that he has received consulting fees and other remuneration from Genentech.

CHICAGO – A number of questions remain regarding the safety and efficacy of rituximab for severe antineutrophil cytoplasmic antibody–associated vasculitis, according to Dr. Phillip Seo.

For example, it remains unclear how the sickest patients – such as those with ANCA-associated vasculitis (AAV), plus renal or respiratory failure – should be managed, and it also remains to be seen what the true effects of the drop in immunoglobulin levels that are seen after several treatment cycles may be, said Dr. Seo said at a symposium sponsored by the American College of Rheumatology.

Rituximab, a chimeric monoclonal antibody against the protein CD20 that is primarily found on the surface of B cells, was first approved in the United States in 2006 for use in combination with methotrexate for adult rheumatoid arthritis patients who failed to respond adequately to TNF (tumor necrosis factor)–antagonist therapies. On April 19, it received a new U.S. Food and Drug Administration approval for use – along with a corticosteroid – in the treatment of Wegener’s granulomatosis and microscopic polyangiitis.

The new approval for these indications was based on findings from the 6-month remission-induction phase of the randomized, double-blind, multicenter, active-controlled RAVE (Rituximab in ANCA-Associated Vasculitis) trial. The RAVE findings demonstrated that rituximab is not inferior to cyclophosphamide for remission induction at 6 months in patients with these severe forms of ANCA-associated vasculitis. Data from an 18-month maintenance phase have not yet been published.

The remission-induction data are of particular interest for patients who fail to respond to cyclophosphamide, or who aren’t candidates for treatment with the cytotoxic agent, which has been the cornerstone of therapy in these diseases. In very young patients, for example, there may be concerns about future fertility that would preclude the use of cyclophosphamide. In the elderly, there may be concerns about bone marrow suppression, said Dr. Seo, codirector of the vasculitis center at Johns Hopkins University, Baltimore.

Indeed, data from the 1970s from the National Institutes of Health, which established cyclophosphamide as a mainstay of treatment for AAV, showed that about 25% of patients have an incomplete response even after 3-5 years of therapy. Intolerance is also an issue, particularly for those with hemorrhagic cystitis or bone marrow suppression resulting from prior exposures, he said.

The 6-month data from RAVE, which were published in July, provide some hope for such patients; the data showed that outcomes were statistically similar in 197 patients who were randomized to treatment with daily oral prednisone (1 mg/kg per day up to 80 mg/day) and either a "very standard course" of oral cyclophosphamide (2 mg/kg per day for 3-6 months, followed by azathioprine to maintain remission) plus rituximab placebo, or rituximab (375 mg/m² infusions once weekly for 4 weeks) plus cyclophosphamide placebo (N. Engl. J. Med. 2010; 363:221-32), Dr. Seo said.

Not only was rituximab shown to be noninferior to cyclophosphamide for inducing complete remission with steroid taper, but treatment response did not differ significantly by disease type. However, patients with Wegener’s granulomatosis trended toward having a slightly better treatment response, he noted.

Treatment response was, however, significantly better with rituximab among those with severe disease flare at study baseline.

"Those [severe flare] patients do much better when they get rituximab ... and in fact this might highlight an important use for rituximab in the future," he said.

However, because patients with renal or respiratory failure were ineligible for the trial, it remains unclear whether rituximab is a viable option for these patients.

"So, although I think rituximab still might work, there’s not really any data with any of these patients," he said.

Also, long-term treatment may be a concern. Many patients receive multiple courses, and their immunoglobulin levels start to drop after about five cycles of rituximab.

"The data seem to indicate that this doesn’t matter and doesn’t seem to be associated with any increased risk of infection. Yet emotionally, I find that so hard to believe," Dr. Seo said, adding that this "is something I’m going to be watching for in the near future."

A final concern mentioned by Dr. Seo is the risk of progressive multifocal leukoencephalopathy (PML), which used to be a concern mainly in patients with HIV/AIDS or in patients receiving cancer chemotherapy. "Unfortunately we now have to talk about it as well," he said.

The majority of patients with rheumatic illness who develop PML after treatment with rituximab have received multiple courses of immunosuppression leading up to rituximab, and this likely explains the majority of cases, but it doesn’t explain all cases.

"So this is a story that continues to evolve," he said.

Dr. Seo disclosed that he has received consulting fees and other remuneration from Genentech.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – Extra-articular manifestations of rheumatoid arthritis still affect more than 40% of patients, and although the incidence of some severe manifestations, such as vasculitis, has declined over time, the incidence of others has increased, and many of these manifestations can adversely affect prognosis and increase mortality.

The 10-year cumulative incidence for all extra-articular manifestations of RA was nearly 50% in a cohort of 463 patients with incident RA in 1995-2007 who were followed through the end of 2008, which is similar to the 46% incidence in a similar cohort of 197 patients who were followed from 1985 to 1994. However, severe manifestations – including ocular disease and vasculitis – occurred in about 7% and 9% of patients in the cohorts, respectively, reported Dr. Eric Matteson at a symposium sponsored by the American College of Rheumatology.

The findings, which were published online April 1 in the Journal of Rheumatology, are from a follow-up of a retrospective, longitudinal, population-based study involving the first cohort. Both cohorts included residents from a single county in Minnesota who were at least 18 years of age and who met at least four of the American College of Rheumatology criteria for RA (J. Rheumatol. 2011 April 1 [doi:10.3899/jrheum.101133]).

The most striking finding was the reduction in the incidence of vasculitis, which affected 3.6% of patients in the earlier cohort, but only 0.6% in the recent cohort, said Dr. Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minn.

Episcleritis, neuropathy, xerostomia, cervical myelopathy, pulmonary fibrosis, Sjögren’s syndrome, and keratoconjunctivitis sicca (KCS) also occurred less often in the later cohort, whereas subcutaneous nodules, pleuritis, pericarditis, and bronchiolitis obliterans-organizing pneumonia (BOOP) all occurred slightly more often in the later cohort.

The study also showed that the occurrence of a second extra-articular manifestation was reduced significantly in the second cohort (hazard ratio, 0.5), and that having any extra-articular manifestation was significantly associated with an increased risk of mortality (HR, 2.0). No additional increase in mortality risk was seen with severe or second extra-articular manifestations, Dr. Matteson noted.

The reasons for the decline in severe manifestations and second manifestations likely include more aggressive treatment strategies – and perhaps the use of biologics – in recent years; more vigorous disease control throughout the course of disease; and possibly secular trends, such as reduced smoking and other as-yet unidentified factors, he said.

Predictors of extra-articular manifestations include smoking, erosive severe joint disease, the need for disease-modifying antirheumatic drugs or biologic response modifiers, and seropositivity for ANA (antinuclear antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibody). Other genetic or environmental factors that are not yet fully understood might also contribute, he said.

Management of extra-articular manifestations should be guided by the organ system involved, but steroids are a mainstay of treatment. Treatments that control synovitis, including NSAIDs, are often effective as well.

For severe manifestations, treatment with glucocorticoids is often needed for at least 2 months. The role of pulse glucocorticoids, although popular, has not been established by randomized, controlled studies, Dr. Matteson said.

In fact, there is a dearth of data regarding treatment of these manifestations in general, he said, noting that cytotoxic drugs are sometimes used, particularly in patients with vasculitis or inflammatory eye disease, and that the role of newer agents – such as anti–B-cell therapy, abatacept, and tumor necrosis factor antagonists – is unclear, as there is anecdotal evidence of both successful and detrimental effects.

Dr. Matteson disclosed that he has received grant support from, and/or served as an investigator or consultant for Amgen, Biogen-IDEC, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Mayo Foundation, National Institutes of Health, Novartis, Pfizer, and UCB.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – The prevalence of ankylosing spondylitis is greatly underestimated, and diagnosis is typically delayed, according to Dr. Michael Weisman.

A 1998 report by the National Arthritis Data Workgroup stated that there are an estimated 2.1 cases of ankylosing spondylitis (AS) per 1,000 individuals older than age 15 years. But this widely cited estimate that 0.21% of the U.S. population has AS was based on classification criteria that required radiographic evidence of AS, said Dr. Weisman director of the division of rheumatology and professor of medicine at Cedars-Sinai Medical Center, Los Angeles.

"This was not a real epidemiologic survey. This was a grossly underestimated prevalence of AS" in the United States, he said, explaining that the researchers relied on the modified New York criteria for AS, which requires not only clinical features, but radiographic changes.

The problem is that radiographic changes take time, and there is a long preradiographic stage in AS during which patients have symptoms for years before developing x-ray changes in sacroiliac joints.

"So when you use modified New York criteria for classification, and you misuse it for diagnosis, you’re going to grossly underestimate the frequency of this disease in the population," he said.

Additionally, studies consistently show that there is an average delay in diagnosis of at least 7-9 years for AS, he said, noting that this is because AS is hidden from obvious view, imaging techniques are needed to make the diagnosis, and the disease is often not suspected because of "the whole ubiquitous idea of low back pain in the population" (Curr. Opin. Rheumatol. 2000;12:239-47).

Also, that study showed that diagnosis in women is delayed even more than in men, and other studies indicate that women have largely been underdiagnosed, Dr. Weisman said, noting that he was taught during training that AS occurs in a 10:1 male-female ratio. The latest data show that it is more like 3:1.

So how many people really have AS? There have been very few prevalence studies, but the latest compilation of data shows that newer prevalence estimates for AS and spondyloarthritis in general vary widely, from 0.52% to 1.3% in the United States, which suggests that the prevalence may be higher than the current estimated 0.6% prevalence of rheumatoid arthritis in the United States. The estimates of AS/spondyloarthritis in other parts of the world are even higher. The estimated prevalence in Norway, for example, ranges up to 6.7%.

A marked north/south gradient also exists in prevalence, and it mirrors the north/south gradient of HLA (human leukocyte antigen)–B27 gene prevalence in the indigenous populations worldwide, which is "tremendously variable." HLA-B27 positivity is very high in northern areas, along with a higher prevalence of AS in northern areas.

These findings can be helpful for improving diagnosis, he said.

To make a correct – and earlier – diagnosis, use your perspective on inflammatory back pain, Dr. Weisman advised.

"Inflammatory back pain will be, for you, the greatest clue to be able to hone in on this diagnosis," he said.

Onset at a young age, relatively long duration of pain, associated morning stiffness, awakening in the middle of the night, and no improvement with rest are classic signs of inflammatory back pain. In fact, at least one study has shown that among those with chronic back pain, about 5% will have AS; but in those with inflammatory back pain the probability is tripled to about 14%-15%. Adding other features can further improve diagnosis.

An emerging understanding of genetic influences, for example, is proving helpful for diagnosis. Heritability for AS is greater than 90%, with HLA-B serving as the major disease-associated locus. The HLA-B27 gene marker is present in about 90% of AS cases, although only about 5% of HLA-B27–positive individuals develop AS.

"So the current model is that AS is largely a monogenic disease with multiple modifying genes," Dr. Weisman said.

The ERAP1 and IL23R genes are other players.

Assuming a frequency of a low AS prevalence estimate of 0.4%, HLA-B27 confers a probability of having AS of 3.6%. HLA-B27 along with ERAP1 increases that to about 10%, and the addition of both ERAP1 and IL23R increases it further to about 23%, Dr. Weisman said.

If you look at inflammatory back pain patients, and thus assume a lower bound estimate of AS of about 10% in that population, the addition of B27 positivity increases AS likelihood to about 50%. The addition of ERAP1 and IL23R positivity increases AS likelihood to 80%-90%, he said.

However, these genes add only a small amount to the frequency of the genetic association in this disease, and there are certain caveats that must be considered, Dr. Weisman said. For example, the ERAP1 association with AS is not seen in the Chinese population, and the ERAP1 association is only found in those with HLA-B27 positivity, which implies a gene-gene interaction.

There remains a great deal of work to be done to define the genetic bases of AS, he said.

In the meantime, efforts to better determine AS prevalence based on newer classification criteria are underway.

Unlike the modified New York criteria which used clear-cut radiographic sacroiliitis, new classification criteria for axial spondyloarthritis developed by the Assessments in Ankylosing Spondylitis Working Group uses additional features to increase sensitivity. One set of criteria uses HLA-B27 plus two additional features of spondyloarthritis for AS classification, and one uses sacroiliitis on imaging plus one spondyloarthritis feature to make a diagnosis. This increases sensitivity of screening to over 80%, he said (Ann. Rheum. Dis. 2009;68:777-83).

Furthermore, a screening questionnaire developed and published last year by Cedars-Sinai Medical Center to help improve diagnosis and to identify more patients on a population basis using various clinical features will be applied to National Health and Nutrition Examination Survey data from 2009-2010, which included a new survey on inflammatory back pain and spondyloarthritis. Together these seek to provide the first U.S. national inflammatory back pain estimate, and the first national U.S. study of HLA-B27 prevalence, Dr. Weisman said.

"With these two, we’ll be able to find the lower bound of the true prevalence of ankylosing spondylitis in the United States," he said.

Dr. Weisman had no disclosures to report.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.

CHICAGO – Reverse shoulder arthroplasty provides a surgical option for improving pain and ability in patients who have both arthritis and massive rotator cuff tear.

Before the procedure was approved for use in the United States in 2005, patients with this combination of conditions were very difficult to manage, said Dr. Matthew Saltzman at a symposium sponsored by the American College of Rheumatology.

"We didn’t have a solution for this problem for many, many years, but now I think we really do," said Dr. Saltzman, an orthopedic surgeon specializing in shoulder and elbow surgery at Northwestern University, Chicago.

Reverse shoulder arthroplasty basically changes the mechanics of the shoulder. It involves putting the ball in the socket, and putting the socket where the ball used to be, he said, adding that it’s "a strange concept, but it actually works."

"With reverse shoulder arthroplasty, you’re actually medializing the center of rotation, and this can be done to varying degrees depending on the implant design," he said, explaining that the procedure changes the tension on the deltoid muscle and allows the deltoid, rather than the irreparable rotator cuff musculature, to lift the arm.

Dr. Saltzman described two cases involving elderly women who underwent reverse shoulder arthroplasty and had excellent outcomes at 6-12 months. One was an 84-year-old who presented with a massive cuff tear as well as arthritis-related joint damage and loss of the joint space. Like many patients with these conditions, she had severe pain, pseudoparalysis of the shoulder, and resulting lack of function; she was able to lift her arm to only about 20 degrees.

At 6 months after the operation, she had no pain and was able to elevate her arm and rotate the arm out to the side.

The other patient was an 86-year-old who had previously lived independently, but who had slipped on ice and sustained multiple fractures of her shoulder. Although her problem wasn’t arthritis related, the reverse shoulder arthroplasty was successful, and she was able to return to independent living.

Findings from a study involving 240 consecutive reverse shoulder arthroplasty procedures in 232 patients (average age, nearly 73 years) showed that average forward elevation increased from 86 degrees to 137 degrees, and average constant score (a validated measure of shoulder function) improved from 23 to 60 at the latest follow-up, indicating substantial improvement, Dr. Saltzman said (J. Bone Joint Surg. Am. 2007;89:1476-85).

In that study, patients with cuff tear arthropathy, osteoarthritis plus cuff tear, or massive cuff tear fared better, whereas those with posttraumatic arthritis and those undergoing revision arthroplasty had worse outcomes.

Of course, patients need to be healthy enough to withstand surgery, but in appropriately selected patients this procedure provides a really nice result, he said.

"You’re taking a very severe problem and giving people a much better quality of life," he added.

Dr. Saltzman disclosed that he serves on the speakers bureau of Carefusion, has made paid presentations for DJO Surgical, and has received research support from Arthrex.