Sally Koch Kubetin

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, according to an analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are important in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of Harvard School of Public Health, Boston, and her associates.

According to previous research, the mechanism of the association might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels in obese adolescents could be an important risk factor, according to Dr. Munger.

The Nurses' Health Study (NHS) began in 1976 and involved 121,700 female, married registered nurses aged 30-55 years and living in 1 of 11 states at the time of enrollment.

The Nurses' Health Study II (NSHII) involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in 1 of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable in the assessment by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite, 74 probable.

Obesity during adolescence and adulthood was assessed using body mass index. The baseline questionnaires in 1976 (NHS) and 1989 (NHSII) included current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study.

Women with MS weighed less than did unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with those of previous studies.

Dr. Munger reported receiving travel and speaker honoraria from the Consortium of Multiple Sclerosis Centers and speaker honoraria from the National Multiple Sclerosis Society. Her associates reported several disclosures.

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, according to an analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are important in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of Harvard School of Public Health, Boston, and her associates.

According to previous research, the mechanism of the association might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels in obese adolescents could be an important risk factor, according to Dr. Munger.

The Nurses' Health Study (NHS) began in 1976 and involved 121,700 female, married registered nurses aged 30-55 years and living in 1 of 11 states at the time of enrollment.

The Nurses' Health Study II (NSHII) involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in 1 of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable in the assessment by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite, 74 probable.

Obesity during adolescence and adulthood was assessed using body mass index. The baseline questionnaires in 1976 (NHS) and 1989 (NHSII) included current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study.

Women with MS weighed less than did unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with those of previous studies.

Dr. Munger reported receiving travel and speaker honoraria from the Consortium of Multiple Sclerosis Centers and speaker honoraria from the National Multiple Sclerosis Society. Her associates reported several disclosures.

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, according to an analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are important in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of Harvard School of Public Health, Boston, and her associates.

According to previous research, the mechanism of the association might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels in obese adolescents could be an important risk factor, according to Dr. Munger.

The Nurses' Health Study (NHS) began in 1976 and involved 121,700 female, married registered nurses aged 30-55 years and living in 1 of 11 states at the time of enrollment.

The Nurses' Health Study II (NSHII) involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in 1 of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable in the assessment by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite, 74 probable.

Obesity during adolescence and adulthood was assessed using body mass index. The baseline questionnaires in 1976 (NHS) and 1989 (NHSII) included current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study.

Women with MS weighed less than did unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with those of previous studies.

Dr. Munger reported receiving travel and speaker honoraria from the Consortium of Multiple Sclerosis Centers and speaker honoraria from the National Multiple Sclerosis Society. Her associates reported several disclosures.

New guidelines from the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and design recommendations for observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, noted Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist, who arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity (using a validated index), quality of life (using history, either alone or in addition to a patient-completed measure such as a 0-10 visual analog scale), and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease, including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients need yearly blood tests for cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including PaP smear) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus (especially before the start of immunosuppressive drugs); for tuberculosis (according to local guidelines, especially before the initiation of immunosuppressive drugs); and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the U.S. Centers for Disease Control and Prevention. It is ideal to immunize when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)-specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if the lesions' clinical morphology changes, or if there is no response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the U.S. National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic (central, peripheral, or autonomic) involvement occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult; no specific instrument has been evaluated in clinical practice. Thus, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82). Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice, the authors noted.

New guidelines from the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and design recommendations for observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, noted Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist, who arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity (using a validated index), quality of life (using history, either alone or in addition to a patient-completed measure such as a 0-10 visual analog scale), and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease, including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients need yearly blood tests for cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including PaP smear) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus (especially before the start of immunosuppressive drugs); for tuberculosis (according to local guidelines, especially before the initiation of immunosuppressive drugs); and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the U.S. Centers for Disease Control and Prevention. It is ideal to immunize when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)-specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if the lesions' clinical morphology changes, or if there is no response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the U.S. National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic (central, peripheral, or autonomic) involvement occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult; no specific instrument has been evaluated in clinical practice. Thus, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82). Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice, the authors noted.

New guidelines from the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and design recommendations for observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, noted Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist, who arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity (using a validated index), quality of life (using history, either alone or in addition to a patient-completed measure such as a 0-10 visual analog scale), and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease, including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients need yearly blood tests for cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including PaP smear) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus (especially before the start of immunosuppressive drugs); for tuberculosis (according to local guidelines, especially before the initiation of immunosuppressive drugs); and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the U.S. Centers for Disease Control and Prevention. It is ideal to immunize when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)-specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if the lesions' clinical morphology changes, or if there is no response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the U.S. National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic (central, peripheral, or autonomic) involvement occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult; no specific instrument has been evaluated in clinical practice. Thus, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82). Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

In most cases, anything left out of these recommendations should be considered part of standard good clinical practice, the authors noted.

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

Epidemiology was the word of the day in a sampling of posters presented at the annual meeting of the American College of Rheumatology. Below are three posters that received a lot of attention at this year's meeting. The report on heart failure risk in rheumatoid arthritis was one of this year's blue ribbon–winning posters.

RA Severity Predicts Heart Failure

The risk for new-onset heart failure in patients with RA is greatest in patients with the most severe disease, Dr. Soko Setoguchi of Brigham and Women's Hospital in Boston and her associates reported. The research involves 8,483 patients whose RA was diagnosed by a rheumatologist and who were enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. Patients were followed from the time of registry enrollment until Dec. 15, 2006, or death, whichever happened sooner. Patients' mean age was 59 years, 75% were female, 93% were white, 15% were current smokers, and their mean body mass index was 29 kg/m

Women's RA Risk Is Twice Men's

The lifetime risk for RA has remained “remarkably stable” during 1945-1995, according to Cynthia S. Crowson and her associates from the Mayo Clinic in Olmsted, Minn. For men, the lifetime risk is 1.8%; for women, it ranges from 3.4% to 3.7%. This stability occurred despite a gradual decrease in the incidence of RA from 1955 to the mid-1980s. More recently, women are experiencing an increased incidence, whereas that of men remains steady. The investigators used participants in the population-based incident cohort of Olmsted County who fulfilled the 1987 ACR criteria for RA between 1995 and 2005. These findings come from Poisson regression analyses performed to calculate the observed incidence rate in each sex. Calling the lifetime risk “significant” and women's higher lifetime risk “substantial,” the investigators noted an additional worry in their poster: The lifetime risk may be even higher in some subgroups with high-risk genotypes. This research was funded by the National Institutes of Health.

Uveitis Incidence Established in AS

Noninfectious uveitis is more than 20 times more common in patients with ankylosing spondylitis than in the general population, judging from findings presented by Shelagh M. Szabo of Oxford Outcomes in Vancouver, B.C., and colleagues. Using longitudinal physician billing data from Quebec province, the investigators calculated that 7,663 people were diagnosed with AS between 1998 and 2006 (the AS 1 group); another 3,006 people were diagnosed with AS during that time period and were seen for a related visit at least once during the next year (AS 2). The AS 1 group was designed to maximize sensitivity and the AS 2 group to maximize specificity. The AS 1 patients may have had milder disease. The investigators used a 1% random sample of unaffected individuals from Quebec (the population of which was 7.6 million in 2006) as the control group. The crude 10-year incidence of noninfectious uveitis in the AS 1 patients was 368 cases per 10,000 persons; for the AS 2 group, it was 482 cases per 10,000 persons; in the control group, the incidence was 21 cases per 10,000 persons. The standardized incidence ratio (SIR) for uveitis development during the study period was 18.04 for those in AS 1 vs. the controls. The SIR was 23.88 for those in the AS 2 group vs. controls. Age played a significant factor in incidence, with those in the 20- to 39-year-old age group having the largest risk. In the AS 1 group, the uveitis incidence was 53 cases per 1,000 persons in those aged 20-39 years vs. 33 per 1,000 for those aged 40-59 years, and 8 per 1,000 for those aged 60 years or older. In the AS 2 group, the uveitis incidence was 69 per 1,000 persons in those aged 20-39 years vs. 40 per 1,000 persons for those aged 40-59 years, and 13 per 1,000 for those aged 60 years or older. Several of the researchers were employed by Abbott Laboratories.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult, and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult, and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

New guidelines issued by the European League Against Rheumatism on the monitoring of patients with systemic lupus erythematosus offer advice for clinicians and recommendations for the design of observational studies.

The document includes recommendations on 10 components of patient monitoring. An appendix to the document contains a core set of data to be collected in routine clinical practice. Having such standardized data would be a significant help to research, according to Dr. Marta Mosca of the University of Pisa (Italy) and her fellow authors. The panel included rheumatologists, internists, dermatologists, and a nephrologist. They arrived at the following recommendations after a systematic literature review and numerous consultations:

▸ Patient assessment. Every visit should include assessments of the patient's disease activity, using a validated index; quality of life, determined either by history alone or in addition to a patient-completed measure such as a 0-10 visual analog scale; and comorbidities and drug toxicity. Organ damage should be assessed yearly.

▸ Cardiovascular risk factors. Cardiovascular disease (CVD), including related factors such as smoking, vascular events, physical activity level, oral contraceptive use, hormone therapies, and family history of CVD, should be assessed at baseline and monitored at least once a year thereafter. Similarly, lupus patients also need yearly blood tests for blood cholesterol and glucose levels as well as blood pressure measurement and determination of either body mass index or waist circumference. Patients on glucocorticoids and other lupus patients at particularly high risk for CVD may require more frequent assessment.

▸ Other comorbidities. All patients with SLE should be assessed for osteoporosis risk factors, including adequate calcium and vitamin D intake, regular exercise, and smoking habit. They should be screened and followed for osteoporosis according to either of two existing sets of guidelines: those for postmenopausal women or those for patients on glucocorticoids or other medications that reduce bone mass, such as methotrexate. Cancer screening (including Pap smears) is recommended according to guidelines for the general population.

▸ Infection risk. Lupus patients should be screened for HIV, hepatitis C virus, and hepatitis B virus, especially before the start of immunosuppressive drugs; for tuberculosis, according to local guidelines and especially before the initiation of immunosuppressive drugs; and for cytomegalovirus. Lupus patients should receive inactivated vaccines for influenza and pneumococcus in accordance with guidelines for immunosuppressed patients issued by the Centers for Disease Control and Prevention. It is ideal to do the immunization when the lupus is inactive. The use of other vaccines should be considered on a case-by-case basis. To determine the exact risk for infection, lupus patients should be monitored for neutropenia, severe lymphopenia, and low IgG.

▸ Frequency of assessments. Assessment every 6-12 months is adequate in patients with no disease activity, no organ damage, and no comorbidities. Preventive measures should be stressed during these visits. The committee found no data to suggest an optimal frequency of clinical and laboratory assessment in patients with lupus.

▸ Laboratory assessment. The committee recommended that baseline lab assessment include monitoring antinuclear antibody, anti–double-stranded DNA, anti-Ro, anti-La, anti-RNP, anti-Sm, antiphospholipid, C3, and C4. Reevaluation of antiphospholipid antibodies is necessary in previously negative patients prior to pregnancy, surgery, transplant, and estrogen-containing treatments, or in the presence of a new neurologic or vascular event. Before pregnancy, anti-Ro and anti-La antibodies also should be monitored. Remeasurement of anti-dsDNA and low levels of C3 or C4 may support evidence of disease activity or remission.

At 6- to 12-month intervals, patients with inactive disease should have the following lab tests: complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine (or EGFR), urinalysis, and urine protein:creatinine ratio. Any patient on a specific drug treatment should have that drug monitored as well.

▸ Mucocutaneous involvement. Cutaneous manifestations include lupus erythematosus (LE)–specific lesions, including acute cutaneous LE (CLE), subacute CLE, chronic CLE, and intermittent CLE lesions, and LE-nonspecific lesions. Many conditions may mimic LE and therefore may require an evaluation by an experienced dermatologist as well as a skin biopsy for histologic analysis. Follow-up rebiopsy is recommended if there is a change in the clinical morphology of the lesions, or if there is a lack of response to treatment.

▸ Kidney. Patients with a persistently abnormal urinalysis or raised serum creatinine should have urine protein:creatinine ratio tests, urine microscopy, and renal ultrasound, and should be considered for biopsy referral. Patients with established nephropathy should have protein:creatinine ratio and immunologic tests, urine microscopy, and blood pressure evaluations at least every 3 months for the first 2-3 years. Patients with established chronic renal disease should be followed according to the National Kidney Foundation guidelines for chronic kidney disease (www.kidney.org

▸ Neuropsychiatric manifestations. Neurologic involvement (central, peripheral, or autonomic) occurs frequently in SLE. The most frequent syndromes observed are headache, mood disorders, seizures, cognitive impairment, and cerebrovascular disease. The assessment of neurologic symptoms is difficult, and no specific instrument has been evaluated in clinical practice. Therefore, the guidelines recommend that patients should be monitored by clinical history. Cognitive impairment may be assessed by evaluating memory, attention, concentration, and word-finding difficulties (Ann. Rheum. Dis. 2009 Nov. 5 [doi:10.1136/ard.2009.117200]).

▸ Eye assessment. The incidence of retinopathy among SLE patients who are treated with antimalarial drugs is low (0.5%). Risk factors are age older than 60 years, presence of macular degeneration, retinal dystrophy, obesity, liver disease, renal insufficiency, duration of therapy longer than 5 years, daily dose of hydroxychloroquine greater than 6.5 mg/kg, or chloroquine greater than 3 mg/kg. Recommendations on screening for antimalarial retinopathy include a baseline eye assessment according to published guidelines (Ophthalmology 2002;109:1377-82).

Thereafter, in low-risk patients, no further testing is required for the next 5 years; after the first 5 years of treatment, eye assessment is recommended yearly. In high-risk patients, an eye assessment is recommended yearly. In addition, an eye assessment may be required if there are symptoms suggesting eye involvement by lupus.

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo).

However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have Food and Drug Administration approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial included 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture. The women were randomized to treatment with zoledronic acid alone (137), with both zoledronic acid and teriparatide (137), and with teriparatide alone (138). The zoledronic acid dosage was 5 mg intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Changes in BMD were calculated as the difference of least square means (LSM) from a two-way analysis of variance model calculated including the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 in all three treatment groups.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks. N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively. Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid groups than in the teriparatide group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo).

However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have Food and Drug Administration approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial included 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture. The women were randomized to treatment with zoledronic acid alone (137), with both zoledronic acid and teriparatide (137), and with teriparatide alone (138). The zoledronic acid dosage was 5 mg intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Changes in BMD were calculated as the difference of least square means (LSM) from a two-way analysis of variance model calculated including the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 in all three treatment groups.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks. N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively. Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid groups than in the teriparatide group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo).

However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have Food and Drug Administration approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial included 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture. The women were randomized to treatment with zoledronic acid alone (137), with both zoledronic acid and teriparatide (137), and with teriparatide alone (138). The zoledronic acid dosage was 5 mg intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Changes in BMD were calculated as the difference of least square means (LSM) from a two-way analysis of variance model calculated including the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 in all three treatment groups.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks. N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively. Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid groups than in the teriparatide group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, judging from the results of analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are an important period in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of the Harvard School of Public Health, Boston, and her colleagues.

The exact mechanism of the association remains to be confirmed, but it might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals that have been reported by other researchers. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels of the vitamin seen in obese people during adolescence could be an important risk factor, Dr. Munger said.

The data included in the current analysis came from two large studies. One, the Nurses' Health Study (NHS), began in 1976 and involved 121,700 female, married registered nurses who were between 30 and 55 years of age, and living in one of 11 states at the time of enrollment.

The other was the Nurses' Health Study II (NHSII), which involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in one of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite and 74 were probable.

Obesity during adolescence and adulthood was assessed using body mass index (BMI). The baseline questionnaire completed by the participants in either 1976 (NHS) or 1989 (NHSII) included their current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study (aged 30-55 years in NHS; aged 25-42 years in NHSII).

Women with MS weighed less than unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with findings from previous studies.

Dr. Munger reported receiving honoraria from the Consortium of Multiple Sclerosis Centers and the National Multiple Sclerosis Society. Her associates reported several disclosures.

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, judging from the results of analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are an important period in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of the Harvard School of Public Health, Boston, and her colleagues.

The exact mechanism of the association remains to be confirmed, but it might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals that have been reported by other researchers. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels of the vitamin seen in obese people during adolescence could be an important risk factor, Dr. Munger said.

The data included in the current analysis came from two large studies. One, the Nurses' Health Study (NHS), began in 1976 and involved 121,700 female, married registered nurses who were between 30 and 55 years of age, and living in one of 11 states at the time of enrollment.

The other was the Nurses' Health Study II (NHSII), which involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in one of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite and 74 were probable.

Obesity during adolescence and adulthood was assessed using body mass index (BMI). The baseline questionnaire completed by the participants in either 1976 (NHS) or 1989 (NHSII) included their current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study (aged 30-55 years in NHS; aged 25-42 years in NHSII).

Women with MS weighed less than unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with findings from previous studies.

Dr. Munger reported receiving honoraria from the Consortium of Multiple Sclerosis Centers and the National Multiple Sclerosis Society. Her associates reported several disclosures.

Being obese at 18 years of age can double a woman's later risk for multiple sclerosis, judging from the results of analysis of data from two large, longitudinal cohorts.

The finding that weight during adolescence but not childhood or adulthood is associated with a twofold increased risk for MS further supports a growing body of evidence that the teenage years are an important period in the etiology of the demyelinating disorder, reported Kassandra L. Munger, Sc.D., of the Harvard School of Public Health, Boston, and her colleagues.

The exact mechanism of the association remains to be confirmed, but it might hinge on the low levels of serum 25-hydroxyvitamin D, a marker of vitamin D status, in obese individuals that have been reported by other researchers. Vitamin D is an immunomodulator that has been found to reduce the incidence and progression of MS in animal studies when present in high levels. Current thinking holds that the relatively low levels of the vitamin seen in obese people during adolescence could be an important risk factor, Dr. Munger said.

The data included in the current analysis came from two large studies. One, the Nurses' Health Study (NHS), began in 1976 and involved 121,700 female, married registered nurses who were between 30 and 55 years of age, and living in one of 11 states at the time of enrollment.

The other was the Nurses' Health Study II (NHSII), which involved 116,671 female, married registered nurses who enrolled in 1989 when they were between the ages of 25 and 42 years, and lived in one of 14 states. Participants completed questionnaires on their health behavior and medical information every 2 years.

The researchers identified 241 women diagnosed with MS between 1976 and June 2002 in the NHS cohort. Of these, 166 cases were defined as definite and 75 as probable by the patients' neurologists. Among the NHSII cohort, 352 women were diagnosed with MS between 1989 and June 2003; of these, 278 cases were definite and 74 were probable.

Obesity during adolescence and adulthood was assessed using body mass index (BMI). The baseline questionnaire completed by the participants in either 1976 (NHS) or 1989 (NHSII) included their current weight and height. A later questionnaire completed in 1980 for the NHS cohort and 1989 for the NHSII cohort included data on their weight at age 18. In 1988 (NHS) and 1989 (NHSII), childhood BMI was determined by having women select which of nine silhouettes ranging from very thin to extremely obese best represented their body size at ages 5, 10, and 20 years.

Women with a BMI of 30 kg/m

Women who reported having larger body silhouettes at age 20 also had a twofold greater risk for MS, compared with those who reported a thinner body.

The risk for MS was not affected by obesity in childhood or at the age at the time of enrollment in either study (aged 30-55 years in NHS; aged 25-42 years in NHSII).

Women with MS weighed less than unaffected women. The decrease in relative weight occurred after the diagnosis, a finding that is consistent with findings from previous studies.

Dr. Munger reported receiving honoraria from the Consortium of Multiple Sclerosis Centers and the National Multiple Sclerosis Society. Her associates reported several disclosures.

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Rituximab seems to be the most effective biologic disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis, according to a Cochrane systematic review of the literature. Anakinra appeared to be the least effective of the agents evaluated.

All six biologics studied provided clinically important improvement in pain and disability. However, the degree of relief differed among the agents, which also included abatacept, adalimumab, etanercept, and infliximab.

Absolute improvement (defined as ACR 50) was reported in 51% more people on rituximab than on placebo. Compared with those taking placebo, 42% more people taking adalimumab achieved that level of improvement, as did 40% more people taking etanercept, 26% more people taking abatacept, 24% more people taking infliximab, and 6% more people on anakinra, according to the report's authors, who are all members of the Cochrane Musculoskeletal Group and were led by Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

People on abatacept, etanercept, or rituximab were no more likely than those on placebo to drop out of the trial because of side effects. For infliximab, the absolute difference of people who dropped out of the trial, compared with placebo, was 6%; for anakinra, that difference was 4%; and for adalimumab, that difference was 3%.

The researchers searched the Cochrane Database of Systematic Reviews for literature reviews with the term “rheumatoid” in the title that had concluded by May 20, 2009; included at least one randomized, controlled trial; had clinically relevant outcomes; and included clear inclusion and exclusion criteria for studies. Only trials of adults were considered. The review was limited to studies of standard rheumatoid arthritis dosing regimens of the six agents, used either alone or in combination with another biologic or conventional DMARD, compared with either placebo alone or placebo plus a biologic or conventional DMARD.

Primary outcomes were ACR 50 and withdrawal because of any adverse event. Six reviews were included in this overview. The biologic DMARDs included in this review were abatacept (seven studies), adalimumab (eight studies), anakinra (five studies), etanercept (four studies), infliximab (three studies), and rituximab (three studies) (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858.CD007848.pub2])

The six biologic DMARDs in this overview had similar efficacy for primary outcomes with three exceptions: Anakinra was less effective than etanercept (relative risk, 0.44) and less effective than rituximab (RR, 0.45), and adalimumab was more efficacious than anakinra (RR, 2.34).

In terms of safety, adalimumab was more likely to lead to withdrawal, compared with etanercept (odds ratio, 1.89); anakinra was more likely than etanercept (OR, 2.05), and etanercept was less likely to lead to withdrawal for side effects than was infliximab (OR, 0.37).

Dr. Singh reported receiving speaker honoraria from Abbott Laboratories; research grants from Amgen Inc., Allergan Inc., Takeda Pharmaceutical Co., and Savient Pharmaceuticals Inc.; and a consultant fee from Savient.

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.

Abatacept has been shown to be an effective biologic agent for use in the treatment of rheumatoid arthritis, according to findings of a Cochrane review of seven studies involving almost 3,000 patients.

Of the 2,908 patients in this review, 1,863 were randomized to abatacept and 1,045 to placebo. Most were white women, and their average age was 48–56 years, depending on the trial. Most trials used a dose of 10 mg/kg of abatacept, and patients continued to use a disease-modifying antirheumatic drug in addition to abatacept for the duration of the study, according to the review's authors, Lara Maxwell of the University of Ottawa and Dr. Jasvinder A. Singh of the Minneapolis VA Medical Center.

Patients treated with abatacept were 2.2 times more likely than those on placebo to have an ACR 50 response (the primary end point) at the end of year 1 (relative risk, 2.21). There was a 21% absolute risk difference between the two groups. The number needed to achieve an ACR 50 was five patients.

Physical function significantly improved and both disease activity and pain lessened in patients who were treated with abatacept, compared with placebo.

Findings from one of the seven randomized, controlled trials in the review showed that abatacept significantly slowed radiographic progression of joint damage at 12 months, compared with placebo. However, it is unclear whether that finding had any clinical relevance. The other six studies did not assess ra-diographic progression.

The rate of adverse events was greater in abatacept-treated patients than in those on placebo (RR, 1.05). The number of infections after 12 months was significantly greater in the abatacept group vs. the placebo group (Peto odds ratio, 1.91). Serious adverse events were increased when abatacept was used in combination with other biologics (RR, 2.3), an observation that led the authors to recommend that abatacept should not be used in combination with other biologics to treat RA.

Of the seven studies included in the review, only two were free of any risk of bias arising from flawed methodology. Four of the seven did not address incomplete efficacy outcome data; two of those four also did not address incomplete safety outcome data; and a fifth study provided unclear information on both adequate sequence generation and allocation concealment. In addition, because all the included trials were funded by abatacept's manufacturer, it is possible that the findings overestimated the treatment benefit, according to Ms. Maxwell and Dr. Singh (Cochrane Database Syst. Rev. 2009 Oct. 7 [doi:10.1002/14651858. D007277.pub2]).

The studies that were included in this Cochrane review were identified through an extensive literature search. The selected trials were all randomized, controlled studies evaluating the effectiveness and safety of abatacept either alone or in combination with a DMARD or another biologic, vs. placebo alone or a DMARD or biologic, in patients with moderate to severe RA.

The cost of 1 year of abatacept therapy is estimated to be approximately $22,000. The prevalence of RA among white adults aged older than 18 years in the United States is 0.6%.

Abatacept is the first biologic agent to work by disrupting T-cell activation. The drug is a selective costimulation modulator, inhibiting T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28.

All the trials included in this review were funded by Bristol-Myers Squibb Co., the manufacturer of abatacept.

The authors declared that they received financial support from the University of Ottawa and the Minneapolis VA Medical Center.