BSR Annual Conference 2013

BIRMINGHAM, ENGLAND – Patients with hand or wrist problems from rheumatoid arthritis can significantly benefit from a hand-specific exercise program beyond what is achieved with usual care.

"There was a significant difference in the primary outcome measure [the Michigan Hand Outcomes Questionnaire] in favor of the exercise program and this was actually maintained over the 12-month follow period as well," study investigator Dr. Mark Williams said at the annual meeting of the British Society for Rheumatology. Dr. Williams is a research fellow in the Clinical Trials Unit at the University of Warwick, England, where the trial is being coordinated.

In the randomized, controlled trial called SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand), mean Michigan Hand Outcomes Questionnaire (MHQ) scores at 4 months’ assessment improved from 52.1 at baseline in both groups to 61.1 in the exercise group (n = 246) and 56.6 in the usual care group (n = 244), giving a mean difference in hand function improvement of 4.5 (P less than .0002) in favor of the exercise program.

The effects of the 12-week and home-based intervention were sustained at 12 months’ follow-up, with mean MHQ scores of 60.7 (n = 216) and 56.4 (n = 222) in the exercise and usual care groups, respectively, giving a mean difference of 4.3 (P less than .002).

Clinical guidelines in England and Wales state that patients with RA should have access to specialist hand therapy to help increase strength, movement, and function. Prior to the results of the SARAH trial, however, the evidence upon which this recommendation is based was "rather weak," Dr. Williams observed.

The aims of the study were therefore to determine the clinical effectiveness of an exercise program developed to specifically target the hands and upper limbs in patients with RA hand dysfunction, and then to examine its cost-effectiveness.

The study was performed within 17 National Health Service Trusts in England and included RA patients with pain or dysfunction of the hands or wrist joints who were not taking disease-modifying antirheumatic therapy, or if they were, had been stable on treatment for at least 3 months. The 490 patients randomized in the trial had a median age of 63 years and 10 years’ RA disease duration.

Usual care consisted of one-on-one sessions with a hand therapist and information about joint protection and general exercise advice, with functional splinting if there was a clinical need. In addition to this, the patients who were randomized to the SARAH exercise program received a further five sessions of supervised exercises over a 12-week period; sessions included 11 exercises designed to help with stretching and strengthening of the hand, guidance on a daily exercise program to be performed by patients at home, and strategies to encourage adherence (Physiotherapy 2012;98:121-30).

"In order to get patients to adhere to this exercise plan, which is fairly key, we used behavioral strategies, including an exercise diary and a behavioral action plan," Dr. Williams explained. "This was like a contract between the patient and [his or her] therapist." A total of 438 (89%) patients were followed up at 12 months.

Patient-reported self-efficacy was higher with the exercise program, compared with usual care. Indeed, in a letter recently sent to all the patients who participated in the trial, Dr. Williams noted that, "43% of the patients receiving the SARAH exercise programme and 20% of patients receiving usual care reported some or much improvement."

There was no difference in pain scores between groups, with trends for all participants to report some improvement in pain over time. There was also no difference in the number of adverse events between the groups.

Importantly, the SARAH exercise program was shown to be cost effective, incurring only an additional £100 per patient (approximately US$150) to provide. This means existing health care staff could potentially deliver the program, and with relative ease, the SARAH trial team believes.

Their next step is to see if the intervention’s benefits are extended beyond 12 months. The researchers are also looking at how to best to train healthcare professionals to deliver the program in routine practice in the United Kingdom.

The U.K. National Institute for Health Research Health Technology Assessment Program funded the trial. Dr. Williams had no conflicts of interest.

BIRMINGHAM, ENGLAND – Patients with hand or wrist problems from rheumatoid arthritis can significantly benefit from a hand-specific exercise program beyond what is achieved with usual care.

"There was a significant difference in the primary outcome measure [the Michigan Hand Outcomes Questionnaire] in favor of the exercise program and this was actually maintained over the 12-month follow period as well," study investigator Dr. Mark Williams said at the annual meeting of the British Society for Rheumatology. Dr. Williams is a research fellow in the Clinical Trials Unit at the University of Warwick, England, where the trial is being coordinated.

In the randomized, controlled trial called SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand), mean Michigan Hand Outcomes Questionnaire (MHQ) scores at 4 months’ assessment improved from 52.1 at baseline in both groups to 61.1 in the exercise group (n = 246) and 56.6 in the usual care group (n = 244), giving a mean difference in hand function improvement of 4.5 (P less than .0002) in favor of the exercise program.

The effects of the 12-week and home-based intervention were sustained at 12 months’ follow-up, with mean MHQ scores of 60.7 (n = 216) and 56.4 (n = 222) in the exercise and usual care groups, respectively, giving a mean difference of 4.3 (P less than .002).

Clinical guidelines in England and Wales state that patients with RA should have access to specialist hand therapy to help increase strength, movement, and function. Prior to the results of the SARAH trial, however, the evidence upon which this recommendation is based was "rather weak," Dr. Williams observed.

The aims of the study were therefore to determine the clinical effectiveness of an exercise program developed to specifically target the hands and upper limbs in patients with RA hand dysfunction, and then to examine its cost-effectiveness.

The study was performed within 17 National Health Service Trusts in England and included RA patients with pain or dysfunction of the hands or wrist joints who were not taking disease-modifying antirheumatic therapy, or if they were, had been stable on treatment for at least 3 months. The 490 patients randomized in the trial had a median age of 63 years and 10 years’ RA disease duration.

Usual care consisted of one-on-one sessions with a hand therapist and information about joint protection and general exercise advice, with functional splinting if there was a clinical need. In addition to this, the patients who were randomized to the SARAH exercise program received a further five sessions of supervised exercises over a 12-week period; sessions included 11 exercises designed to help with stretching and strengthening of the hand, guidance on a daily exercise program to be performed by patients at home, and strategies to encourage adherence (Physiotherapy 2012;98:121-30).

"In order to get patients to adhere to this exercise plan, which is fairly key, we used behavioral strategies, including an exercise diary and a behavioral action plan," Dr. Williams explained. "This was like a contract between the patient and [his or her] therapist." A total of 438 (89%) patients were followed up at 12 months.

Patient-reported self-efficacy was higher with the exercise program, compared with usual care. Indeed, in a letter recently sent to all the patients who participated in the trial, Dr. Williams noted that, "43% of the patients receiving the SARAH exercise programme and 20% of patients receiving usual care reported some or much improvement."

There was no difference in pain scores between groups, with trends for all participants to report some improvement in pain over time. There was also no difference in the number of adverse events between the groups.

Importantly, the SARAH exercise program was shown to be cost effective, incurring only an additional £100 per patient (approximately US$150) to provide. This means existing health care staff could potentially deliver the program, and with relative ease, the SARAH trial team believes.

Their next step is to see if the intervention’s benefits are extended beyond 12 months. The researchers are also looking at how to best to train healthcare professionals to deliver the program in routine practice in the United Kingdom.

The U.K. National Institute for Health Research Health Technology Assessment Program funded the trial. Dr. Williams had no conflicts of interest.

BIRMINGHAM, ENGLAND – Patients with hand or wrist problems from rheumatoid arthritis can significantly benefit from a hand-specific exercise program beyond what is achieved with usual care.

"There was a significant difference in the primary outcome measure [the Michigan Hand Outcomes Questionnaire] in favor of the exercise program and this was actually maintained over the 12-month follow period as well," study investigator Dr. Mark Williams said at the annual meeting of the British Society for Rheumatology. Dr. Williams is a research fellow in the Clinical Trials Unit at the University of Warwick, England, where the trial is being coordinated.

In the randomized, controlled trial called SARAH (Strengthening and Stretching for Rheumatoid Arthritis of the Hand), mean Michigan Hand Outcomes Questionnaire (MHQ) scores at 4 months’ assessment improved from 52.1 at baseline in both groups to 61.1 in the exercise group (n = 246) and 56.6 in the usual care group (n = 244), giving a mean difference in hand function improvement of 4.5 (P less than .0002) in favor of the exercise program.

The effects of the 12-week and home-based intervention were sustained at 12 months’ follow-up, with mean MHQ scores of 60.7 (n = 216) and 56.4 (n = 222) in the exercise and usual care groups, respectively, giving a mean difference of 4.3 (P less than .002).

Clinical guidelines in England and Wales state that patients with RA should have access to specialist hand therapy to help increase strength, movement, and function. Prior to the results of the SARAH trial, however, the evidence upon which this recommendation is based was "rather weak," Dr. Williams observed.

The aims of the study were therefore to determine the clinical effectiveness of an exercise program developed to specifically target the hands and upper limbs in patients with RA hand dysfunction, and then to examine its cost-effectiveness.

The study was performed within 17 National Health Service Trusts in England and included RA patients with pain or dysfunction of the hands or wrist joints who were not taking disease-modifying antirheumatic therapy, or if they were, had been stable on treatment for at least 3 months. The 490 patients randomized in the trial had a median age of 63 years and 10 years’ RA disease duration.

Usual care consisted of one-on-one sessions with a hand therapist and information about joint protection and general exercise advice, with functional splinting if there was a clinical need. In addition to this, the patients who were randomized to the SARAH exercise program received a further five sessions of supervised exercises over a 12-week period; sessions included 11 exercises designed to help with stretching and strengthening of the hand, guidance on a daily exercise program to be performed by patients at home, and strategies to encourage adherence (Physiotherapy 2012;98:121-30).

"In order to get patients to adhere to this exercise plan, which is fairly key, we used behavioral strategies, including an exercise diary and a behavioral action plan," Dr. Williams explained. "This was like a contract between the patient and [his or her] therapist." A total of 438 (89%) patients were followed up at 12 months.

Patient-reported self-efficacy was higher with the exercise program, compared with usual care. Indeed, in a letter recently sent to all the patients who participated in the trial, Dr. Williams noted that, "43% of the patients receiving the SARAH exercise programme and 20% of patients receiving usual care reported some or much improvement."

There was no difference in pain scores between groups, with trends for all participants to report some improvement in pain over time. There was also no difference in the number of adverse events between the groups.

Importantly, the SARAH exercise program was shown to be cost effective, incurring only an additional £100 per patient (approximately US$150) to provide. This means existing health care staff could potentially deliver the program, and with relative ease, the SARAH trial team believes.

Their next step is to see if the intervention’s benefits are extended beyond 12 months. The researchers are also looking at how to best to train healthcare professionals to deliver the program in routine practice in the United Kingdom.

The U.K. National Institute for Health Research Health Technology Assessment Program funded the trial. Dr. Williams had no conflicts of interest.

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BIRMINGHAM, ENGLAND – The risk of heart attack appears to be lower in patients treated with anti–tumor necrosis factor therapy than with conventional disease-modifying antirheumatic drugs.

Patients treated with the biologic agents had a 30% lower risk for having a myocardial infarction, based on data from the British Society for Rheumatology Biologics Register (BSRBR) for rheumatoid arthritis. However, no differences were detected in 30-day or 1-year mortality rates (adjusted hazard ratios of 0.9 and 0.97, respectively).

"There seems to be a signal that subjects ever exposed to anti-TNF therapy were potentially at reduced risk for developing an MI," Dr. Audrey Low said in an interview at the British Society for Rheumatology annual conference.

Dr. Low, a clinical research fellow in the Arthritis Research UK Epidemiology Unit, University of Manchester, England, explained that traditional risk factors do not fully account for the well-known increased risk for cardiovascular disease in patients with rheumatoid arthritis. Underlying inflammation might play a role, and it was hypothesized that anti-TNF therapy might help to reduce this inflammation, with subsequent cardiovascular benefits.

The BSRBR-RA is one of the largest biologics registers in the world and has been running for more than 10 years. The register currently includes data on more than 20,000 participants treated with either anti-TNF agents or nonbiologic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate.

The present study used data collated between 2001 and 2008 on 11,536 patients treated with anti-TNF drugs licensed at the time in the United Kingdom (etanercept, infliximab, and adalimumab), and 3,225 patients who received nonbiologic DMARDs. Patients with prior MI or angina were excluded, and patients were followed up through April 2010 or until death, incident MI, or date of last clinician assessment, whichever came first.

Patients treated with anti-TNF therapy were younger than those given nonbiologic DMARDs, with a mean age of 56 years versus 60 years at recruitment into the BSRBR-RA. They also tended to have higher disease activity and longer disease duration (11 years vs. 6 years). There were similar percentages of patients with hypertension (29% vs. 32%), diabetes (6% for both), and a history of ever having smoked (59% vs. 62%).

There were 224 incident MIs in the anti-TNF–treated group at a median follow-up of 6 years per person, and 52 heart attacks in the nonbiologic DMARD–treated group at a median follow-up of 4 years per person. "Even though the study has been running for over 10 years, the amount of follow-up per person is between 4 and 6 years," Dr. Low observed.

The unadjusted hazard ratio for MI risk was 0.9, and it increased to 1.2 when adjusted for age and gender. "The hazard ratio goes up as you’d expect," Dr. Low observed. "People in the anti-TNF cohort are younger, and there are more females [77% vs. 74% for nonbiologic DMARDs]."

After adjustment for risk factors, analysis gave a hazard ratio of 0.7 in favor of anti-TNFs reducing the risk for MI. The risk factors included disease-specific factors (age, gender, disease duration, disease activity, steroid exposure, number of previous nonbiologic DMARDs received, and year of entry into the study), as well as traditional cardiovascular risk factors (hypertension, diabetes, smoking, chronic obstructive pulmonary disease, antiplatelet therapy, and use of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors). "Statins were also included in the adjustment," Dr. Low confirmed.

The possible reduction in the risk for heart attack is another potential benefit of anti-TNFs that can be discussed with patients, she suggested, although patients would of course not be put on these drugs in order to reduce their cardiovascular risk.

Why anti-TNFs have this effect is still not clear. Dr. Low said. "It’s going to be very difficult to tease out whether it’s the inflammation that has been reduced by the anti-TNF therapy or whether anti-TNF therapy affects other factors, such as hypertension and lipids, but I don’t think we can say that for certain from this analysis.

Further research will look at the effect of anti-TNFs on the severity of MI to see if there is any difference from nonbiologic DMARDs.

The BSRBR is funded by a grant from the British Society for Rheumatology (BSR), which receives funding from multiple drug companies. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR. Dr. Low had no conflicts of interest.

BIRMINGHAM, ENGLAND – The risk of heart attack appears to be lower in patients treated with anti–tumor necrosis factor therapy than with conventional disease-modifying antirheumatic drugs.

Patients treated with the biologic agents had a 30% lower risk for having a myocardial infarction, based on data from the British Society for Rheumatology Biologics Register (BSRBR) for rheumatoid arthritis. However, no differences were detected in 30-day or 1-year mortality rates (adjusted hazard ratios of 0.9 and 0.97, respectively).

"There seems to be a signal that subjects ever exposed to anti-TNF therapy were potentially at reduced risk for developing an MI," Dr. Audrey Low said in an interview at the British Society for Rheumatology annual conference.

Dr. Low, a clinical research fellow in the Arthritis Research UK Epidemiology Unit, University of Manchester, England, explained that traditional risk factors do not fully account for the well-known increased risk for cardiovascular disease in patients with rheumatoid arthritis. Underlying inflammation might play a role, and it was hypothesized that anti-TNF therapy might help to reduce this inflammation, with subsequent cardiovascular benefits.

The BSRBR-RA is one of the largest biologics registers in the world and has been running for more than 10 years. The register currently includes data on more than 20,000 participants treated with either anti-TNF agents or nonbiologic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate.

The present study used data collated between 2001 and 2008 on 11,536 patients treated with anti-TNF drugs licensed at the time in the United Kingdom (etanercept, infliximab, and adalimumab), and 3,225 patients who received nonbiologic DMARDs. Patients with prior MI or angina were excluded, and patients were followed up through April 2010 or until death, incident MI, or date of last clinician assessment, whichever came first.

Patients treated with anti-TNF therapy were younger than those given nonbiologic DMARDs, with a mean age of 56 years versus 60 years at recruitment into the BSRBR-RA. They also tended to have higher disease activity and longer disease duration (11 years vs. 6 years). There were similar percentages of patients with hypertension (29% vs. 32%), diabetes (6% for both), and a history of ever having smoked (59% vs. 62%).

There were 224 incident MIs in the anti-TNF–treated group at a median follow-up of 6 years per person, and 52 heart attacks in the nonbiologic DMARD–treated group at a median follow-up of 4 years per person. "Even though the study has been running for over 10 years, the amount of follow-up per person is between 4 and 6 years," Dr. Low observed.

The unadjusted hazard ratio for MI risk was 0.9, and it increased to 1.2 when adjusted for age and gender. "The hazard ratio goes up as you’d expect," Dr. Low observed. "People in the anti-TNF cohort are younger, and there are more females [77% vs. 74% for nonbiologic DMARDs]."

After adjustment for risk factors, analysis gave a hazard ratio of 0.7 in favor of anti-TNFs reducing the risk for MI. The risk factors included disease-specific factors (age, gender, disease duration, disease activity, steroid exposure, number of previous nonbiologic DMARDs received, and year of entry into the study), as well as traditional cardiovascular risk factors (hypertension, diabetes, smoking, chronic obstructive pulmonary disease, antiplatelet therapy, and use of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors). "Statins were also included in the adjustment," Dr. Low confirmed.

The possible reduction in the risk for heart attack is another potential benefit of anti-TNFs that can be discussed with patients, she suggested, although patients would of course not be put on these drugs in order to reduce their cardiovascular risk.

Why anti-TNFs have this effect is still not clear. Dr. Low said. "It’s going to be very difficult to tease out whether it’s the inflammation that has been reduced by the anti-TNF therapy or whether anti-TNF therapy affects other factors, such as hypertension and lipids, but I don’t think we can say that for certain from this analysis.

Further research will look at the effect of anti-TNFs on the severity of MI to see if there is any difference from nonbiologic DMARDs.

The BSRBR is funded by a grant from the British Society for Rheumatology (BSR), which receives funding from multiple drug companies. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR. Dr. Low had no conflicts of interest.

BIRMINGHAM, ENGLAND – The risk of heart attack appears to be lower in patients treated with anti–tumor necrosis factor therapy than with conventional disease-modifying antirheumatic drugs.

Patients treated with the biologic agents had a 30% lower risk for having a myocardial infarction, based on data from the British Society for Rheumatology Biologics Register (BSRBR) for rheumatoid arthritis. However, no differences were detected in 30-day or 1-year mortality rates (adjusted hazard ratios of 0.9 and 0.97, respectively).

"There seems to be a signal that subjects ever exposed to anti-TNF therapy were potentially at reduced risk for developing an MI," Dr. Audrey Low said in an interview at the British Society for Rheumatology annual conference.

Dr. Low, a clinical research fellow in the Arthritis Research UK Epidemiology Unit, University of Manchester, England, explained that traditional risk factors do not fully account for the well-known increased risk for cardiovascular disease in patients with rheumatoid arthritis. Underlying inflammation might play a role, and it was hypothesized that anti-TNF therapy might help to reduce this inflammation, with subsequent cardiovascular benefits.

The BSRBR-RA is one of the largest biologics registers in the world and has been running for more than 10 years. The register currently includes data on more than 20,000 participants treated with either anti-TNF agents or nonbiologic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate.

The present study used data collated between 2001 and 2008 on 11,536 patients treated with anti-TNF drugs licensed at the time in the United Kingdom (etanercept, infliximab, and adalimumab), and 3,225 patients who received nonbiologic DMARDs. Patients with prior MI or angina were excluded, and patients were followed up through April 2010 or until death, incident MI, or date of last clinician assessment, whichever came first.

Patients treated with anti-TNF therapy were younger than those given nonbiologic DMARDs, with a mean age of 56 years versus 60 years at recruitment into the BSRBR-RA. They also tended to have higher disease activity and longer disease duration (11 years vs. 6 years). There were similar percentages of patients with hypertension (29% vs. 32%), diabetes (6% for both), and a history of ever having smoked (59% vs. 62%).

There were 224 incident MIs in the anti-TNF–treated group at a median follow-up of 6 years per person, and 52 heart attacks in the nonbiologic DMARD–treated group at a median follow-up of 4 years per person. "Even though the study has been running for over 10 years, the amount of follow-up per person is between 4 and 6 years," Dr. Low observed.

The unadjusted hazard ratio for MI risk was 0.9, and it increased to 1.2 when adjusted for age and gender. "The hazard ratio goes up as you’d expect," Dr. Low observed. "People in the anti-TNF cohort are younger, and there are more females [77% vs. 74% for nonbiologic DMARDs]."

After adjustment for risk factors, analysis gave a hazard ratio of 0.7 in favor of anti-TNFs reducing the risk for MI. The risk factors included disease-specific factors (age, gender, disease duration, disease activity, steroid exposure, number of previous nonbiologic DMARDs received, and year of entry into the study), as well as traditional cardiovascular risk factors (hypertension, diabetes, smoking, chronic obstructive pulmonary disease, antiplatelet therapy, and use of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors). "Statins were also included in the adjustment," Dr. Low confirmed.

The possible reduction in the risk for heart attack is another potential benefit of anti-TNFs that can be discussed with patients, she suggested, although patients would of course not be put on these drugs in order to reduce their cardiovascular risk.

Why anti-TNFs have this effect is still not clear. Dr. Low said. "It’s going to be very difficult to tease out whether it’s the inflammation that has been reduced by the anti-TNF therapy or whether anti-TNF therapy affects other factors, such as hypertension and lipids, but I don’t think we can say that for certain from this analysis.

Further research will look at the effect of anti-TNFs on the severity of MI to see if there is any difference from nonbiologic DMARDs.

The BSRBR is funded by a grant from the British Society for Rheumatology (BSR), which receives funding from multiple drug companies. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR. Dr. Low had no conflicts of interest.

BIRMINGHAM, ENGLAND – In the first 6 months after the diagnosis of polymyalgia rheumatica, the risk of cancer was almost doubled, with a hazard ratio of 1.96, in a primary care–based matched cohort study of more than 12,000 individuals.

After 6 months, the cancer risk subsided, with a hazard ratio of 1.03 at 6-12 months after diagnosis, 1.04 at 1-2 years, 1.05 at 2-5 years, 1.1 at 5-10 years, and 1.00 after 10 years, reported Sara Muller, Ph.D., of the Research Institute for Primary Care & Health Sciences, Keele University, England.

The drop-off in cancer diagnosis may reflect "a differential diagnosis issue. Maybe there are early cancer symptoms that are being diagnosed as PMR [polymyalgia rheumatica]," she added at the British Society for Rheumatology annual conference.

Monitor PMR patients closely for the first 6 months after diagnosis, Dr. Muller advised. Future research needs to try to tease out how to identify PMR patients who might actually have cancer from those whose condition is limited to joint problems.

PMR is the most common inflammatory rheumatologic condition in older adults. The study was performed to see if there was any link between PMR and cancer, as has been seen for rheumatoid arthritis and lymphoma.

Case reports indicate PMR has been misdiagnosed as renal, testicular, gastric, or hematologic (lymphoma) cancer. The results of a Swedish study (Rheumatology 2010;49:1158-63) suggest that cancer risk is slightly increased in patients diagnosed with PMR or giant cell arteritis. These were all secondary care studies, however, so Dr. Muller and her associates decided to look at a primary care population, where most cases of PMR are diagnosed and treated.

Using the U.K. General Practice Research Database (GPRD), now known as the Clinical Practice Research Datalink, the research team identified 2,877 cases of PMR in individuals aged 50 years or older who were diagnosed between 1987 and 1999. Each case was then matched to five individuals without PMR as controls (n = 9,942). The development of cancer was assessed from 1987 to 2011. Patients with a prior history of cancer or vascular disease were excluded from the study. The cohort was 73% female, and the mean age of the study population was 72 years.

The median observation time was 7.8 years, with some patients followed for more than 20 years. During this time, 667 (23.2%) cases of cancer were diagnosed in patients with PMR and 1,938 (19.5%) in those without, giving respective cancer diagnosis rates of 27.7 and 24.4 per 1,000 person-years.

"In those people with PMR, there were more genitourinary cancers, which were mainly prostate cancers, than in those without PMR," observed Dr. Muller. She added that there were also more cancers affecting the lymphatic system and hematopoietic tissue, and unspecified cancers categorized as "other" by the GPRD coding system.

Conversely, PMR patients were less likely than those without PMR to have cancers of the bone, connective tissue, skin and breast, digestive system and peritoneum, and the respiratory tract and intrathoracic organs.

However, these were only trends and not statistically significant. "We could not really look at the statistical significance of these differences in types of cancer because, despite this being possibly one of the largest datasets where you would find this kind of information, we still didn’t really have enough numbers to make any formal statistical analysis," Dr. Muller said.

The Royal College of General Practitioners Scientific Foundation Board supported the research. Dr. Muller had no conflicts of interest.

BIRMINGHAM, ENGLAND – In the first 6 months after the diagnosis of polymyalgia rheumatica, the risk of cancer was almost doubled, with a hazard ratio of 1.96, in a primary care–based matched cohort study of more than 12,000 individuals.

After 6 months, the cancer risk subsided, with a hazard ratio of 1.03 at 6-12 months after diagnosis, 1.04 at 1-2 years, 1.05 at 2-5 years, 1.1 at 5-10 years, and 1.00 after 10 years, reported Sara Muller, Ph.D., of the Research Institute for Primary Care & Health Sciences, Keele University, England.

The drop-off in cancer diagnosis may reflect "a differential diagnosis issue. Maybe there are early cancer symptoms that are being diagnosed as PMR [polymyalgia rheumatica]," she added at the British Society for Rheumatology annual conference.

Monitor PMR patients closely for the first 6 months after diagnosis, Dr. Muller advised. Future research needs to try to tease out how to identify PMR patients who might actually have cancer from those whose condition is limited to joint problems.

PMR is the most common inflammatory rheumatologic condition in older adults. The study was performed to see if there was any link between PMR and cancer, as has been seen for rheumatoid arthritis and lymphoma.

Case reports indicate PMR has been misdiagnosed as renal, testicular, gastric, or hematologic (lymphoma) cancer. The results of a Swedish study (Rheumatology 2010;49:1158-63) suggest that cancer risk is slightly increased in patients diagnosed with PMR or giant cell arteritis. These were all secondary care studies, however, so Dr. Muller and her associates decided to look at a primary care population, where most cases of PMR are diagnosed and treated.

Using the U.K. General Practice Research Database (GPRD), now known as the Clinical Practice Research Datalink, the research team identified 2,877 cases of PMR in individuals aged 50 years or older who were diagnosed between 1987 and 1999. Each case was then matched to five individuals without PMR as controls (n = 9,942). The development of cancer was assessed from 1987 to 2011. Patients with a prior history of cancer or vascular disease were excluded from the study. The cohort was 73% female, and the mean age of the study population was 72 years.

The median observation time was 7.8 years, with some patients followed for more than 20 years. During this time, 667 (23.2%) cases of cancer were diagnosed in patients with PMR and 1,938 (19.5%) in those without, giving respective cancer diagnosis rates of 27.7 and 24.4 per 1,000 person-years.

"In those people with PMR, there were more genitourinary cancers, which were mainly prostate cancers, than in those without PMR," observed Dr. Muller. She added that there were also more cancers affecting the lymphatic system and hematopoietic tissue, and unspecified cancers categorized as "other" by the GPRD coding system.

Conversely, PMR patients were less likely than those without PMR to have cancers of the bone, connective tissue, skin and breast, digestive system and peritoneum, and the respiratory tract and intrathoracic organs.

However, these were only trends and not statistically significant. "We could not really look at the statistical significance of these differences in types of cancer because, despite this being possibly one of the largest datasets where you would find this kind of information, we still didn’t really have enough numbers to make any formal statistical analysis," Dr. Muller said.

The Royal College of General Practitioners Scientific Foundation Board supported the research. Dr. Muller had no conflicts of interest.

BIRMINGHAM, ENGLAND – In the first 6 months after the diagnosis of polymyalgia rheumatica, the risk of cancer was almost doubled, with a hazard ratio of 1.96, in a primary care–based matched cohort study of more than 12,000 individuals.

After 6 months, the cancer risk subsided, with a hazard ratio of 1.03 at 6-12 months after diagnosis, 1.04 at 1-2 years, 1.05 at 2-5 years, 1.1 at 5-10 years, and 1.00 after 10 years, reported Sara Muller, Ph.D., of the Research Institute for Primary Care & Health Sciences, Keele University, England.

The drop-off in cancer diagnosis may reflect "a differential diagnosis issue. Maybe there are early cancer symptoms that are being diagnosed as PMR [polymyalgia rheumatica]," she added at the British Society for Rheumatology annual conference.

Monitor PMR patients closely for the first 6 months after diagnosis, Dr. Muller advised. Future research needs to try to tease out how to identify PMR patients who might actually have cancer from those whose condition is limited to joint problems.

PMR is the most common inflammatory rheumatologic condition in older adults. The study was performed to see if there was any link between PMR and cancer, as has been seen for rheumatoid arthritis and lymphoma.

Case reports indicate PMR has been misdiagnosed as renal, testicular, gastric, or hematologic (lymphoma) cancer. The results of a Swedish study (Rheumatology 2010;49:1158-63) suggest that cancer risk is slightly increased in patients diagnosed with PMR or giant cell arteritis. These were all secondary care studies, however, so Dr. Muller and her associates decided to look at a primary care population, where most cases of PMR are diagnosed and treated.

Using the U.K. General Practice Research Database (GPRD), now known as the Clinical Practice Research Datalink, the research team identified 2,877 cases of PMR in individuals aged 50 years or older who were diagnosed between 1987 and 1999. Each case was then matched to five individuals without PMR as controls (n = 9,942). The development of cancer was assessed from 1987 to 2011. Patients with a prior history of cancer or vascular disease were excluded from the study. The cohort was 73% female, and the mean age of the study population was 72 years.

The median observation time was 7.8 years, with some patients followed for more than 20 years. During this time, 667 (23.2%) cases of cancer were diagnosed in patients with PMR and 1,938 (19.5%) in those without, giving respective cancer diagnosis rates of 27.7 and 24.4 per 1,000 person-years.

"In those people with PMR, there were more genitourinary cancers, which were mainly prostate cancers, than in those without PMR," observed Dr. Muller. She added that there were also more cancers affecting the lymphatic system and hematopoietic tissue, and unspecified cancers categorized as "other" by the GPRD coding system.

Conversely, PMR patients were less likely than those without PMR to have cancers of the bone, connective tissue, skin and breast, digestive system and peritoneum, and the respiratory tract and intrathoracic organs.

However, these were only trends and not statistically significant. "We could not really look at the statistical significance of these differences in types of cancer because, despite this being possibly one of the largest datasets where you would find this kind of information, we still didn’t really have enough numbers to make any formal statistical analysis," Dr. Muller said.

The Royal College of General Practitioners Scientific Foundation Board supported the research. Dr. Muller had no conflicts of interest.

BIRMINGHAM, ENGLAND – Contrary to expectations, metal-on-metal hip resurfacing for osteoarthritis was associated with higher patient survival at 10 years than was total hip arthroplasty in a large, population-based study.

Cumulative mortality rates were 2.8% for hip resurfacing versus 7.3% for cemented total hip replacement (THR; hazard ratio, 0.51). Ten-year mortality rates comparing hip resurfacing to uncemented THR were 2.6% and 3.2%, respectively (HR, 0.64).

Furthermore, the number needed to treat with hip resurfacing to prevent 1 excess death was 29 when compared to cemented THR, and it was 88 when compared to uncemented THR.

"Patients who received a metal-on-metal resurfacing [MoMR] procedure seem to have a long-term survival advantage compared to patients receiving cemented or an uncemented THR," said Dr. Adrian Kendal of the National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit at the University of Oxford, England.

"Our findings were robust after adjustment for known confounders," Dr. Kendal said at the British Society for Rheumatology annual conference. Propensity matching was used in the trial, which took age, gender, comorbidity, rurality, and social deprivation into account.

For the study, data from the English Hospital Episode Statistics database were obtained and linked to Office for National Statistics mortality records for all adults (over age 18) undergoing elective primary hip replacement for osteoarthritis in National Health Service hospitals in England and Wales between April 1999 and March 2012.

After propensity score matching, there were 91,633 procedures performed, of which 12,580 were MoMR, 37,740 were cemented THR, and 41,312 were uncemented THR.

In response to a comment that perhaps people opting for MoMR were more likely to be younger, more active, and hence more likely to exercise, Dr. Kendal conceded that other factors might exist that could have affected survival.

Speculating about why there might be such a difference in survival, he said: "I personally don’t think it’s just the use of cement, because that doesn’t explain the group that received an uncemented total hip replacement."

He added that the way the femur is prepared during THR might be important, regardless of whether or not cement is used. The known risk of thrombotic consequences also could affect survival. In addition, health care inequality might be important, as resurfacing procedures are less common than THR, perhaps because of the lack of specialized centers or dedicated teams.

Commenting on the findings after their presentation, consultant rheumatologist Dr. Alex MacGregor, of the University of East Anglia, Norwich, England, noted that similar data were published on this topic last year (BMJ 2012;344:e3319), but the results had proved somewhat controversial as the authors had a conflict of interest in favor of hip resurfacing.

Dr. MacGregor, who is a member of the National Joint Registry Steering Committee, has been involved in a subsequent reanalysis of the paper’s findings and said that the results will be made public later in the year.

"One of my concerns [with this study] is the use of the 10-year mortality endpoint. If these resurfacing procedures are saving lives, then you would expect to see a survival benefit sooner, say at 90 days," Dr. MacGregor said.

Dr. Kendal responded that they tried to account for this, but the answer will need to come from a properly organized, randomized controlled trial.

"We don’t have a conflict of interest here. If anything, we were perhaps looking for the opposite effect; we were expecting to see an increased mortality rate in the resurfacing group," Dr. Kendal said. "That was not the case as it turned out, so I am reasonably confident that our data support the findings of that BMJ article."

Dr. Kendal and Dr. MacGregor reported no conflicts of interest.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Contrary to expectations, metal-on-metal hip resurfacing for osteoarthritis was associated with higher patient survival at 10 years than was total hip arthroplasty in a large, population-based study.

Cumulative mortality rates were 2.8% for hip resurfacing versus 7.3% for cemented total hip replacement (THR; hazard ratio, 0.51). Ten-year mortality rates comparing hip resurfacing to uncemented THR were 2.6% and 3.2%, respectively (HR, 0.64).

Furthermore, the number needed to treat with hip resurfacing to prevent 1 excess death was 29 when compared to cemented THR, and it was 88 when compared to uncemented THR.

"Patients who received a metal-on-metal resurfacing [MoMR] procedure seem to have a long-term survival advantage compared to patients receiving cemented or an uncemented THR," said Dr. Adrian Kendal of the National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit at the University of Oxford, England.

"Our findings were robust after adjustment for known confounders," Dr. Kendal said at the British Society for Rheumatology annual conference. Propensity matching was used in the trial, which took age, gender, comorbidity, rurality, and social deprivation into account.

For the study, data from the English Hospital Episode Statistics database were obtained and linked to Office for National Statistics mortality records for all adults (over age 18) undergoing elective primary hip replacement for osteoarthritis in National Health Service hospitals in England and Wales between April 1999 and March 2012.

After propensity score matching, there were 91,633 procedures performed, of which 12,580 were MoMR, 37,740 were cemented THR, and 41,312 were uncemented THR.

In response to a comment that perhaps people opting for MoMR were more likely to be younger, more active, and hence more likely to exercise, Dr. Kendal conceded that other factors might exist that could have affected survival.

Speculating about why there might be such a difference in survival, he said: "I personally don’t think it’s just the use of cement, because that doesn’t explain the group that received an uncemented total hip replacement."

He added that the way the femur is prepared during THR might be important, regardless of whether or not cement is used. The known risk of thrombotic consequences also could affect survival. In addition, health care inequality might be important, as resurfacing procedures are less common than THR, perhaps because of the lack of specialized centers or dedicated teams.

Commenting on the findings after their presentation, consultant rheumatologist Dr. Alex MacGregor, of the University of East Anglia, Norwich, England, noted that similar data were published on this topic last year (BMJ 2012;344:e3319), but the results had proved somewhat controversial as the authors had a conflict of interest in favor of hip resurfacing.

Dr. MacGregor, who is a member of the National Joint Registry Steering Committee, has been involved in a subsequent reanalysis of the paper’s findings and said that the results will be made public later in the year.

"One of my concerns [with this study] is the use of the 10-year mortality endpoint. If these resurfacing procedures are saving lives, then you would expect to see a survival benefit sooner, say at 90 days," Dr. MacGregor said.

Dr. Kendal responded that they tried to account for this, but the answer will need to come from a properly organized, randomized controlled trial.

"We don’t have a conflict of interest here. If anything, we were perhaps looking for the opposite effect; we were expecting to see an increased mortality rate in the resurfacing group," Dr. Kendal said. "That was not the case as it turned out, so I am reasonably confident that our data support the findings of that BMJ article."

Dr. Kendal and Dr. MacGregor reported no conflicts of interest.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Contrary to expectations, metal-on-metal hip resurfacing for osteoarthritis was associated with higher patient survival at 10 years than was total hip arthroplasty in a large, population-based study.

Cumulative mortality rates were 2.8% for hip resurfacing versus 7.3% for cemented total hip replacement (THR; hazard ratio, 0.51). Ten-year mortality rates comparing hip resurfacing to uncemented THR were 2.6% and 3.2%, respectively (HR, 0.64).

Furthermore, the number needed to treat with hip resurfacing to prevent 1 excess death was 29 when compared to cemented THR, and it was 88 when compared to uncemented THR.

"Patients who received a metal-on-metal resurfacing [MoMR] procedure seem to have a long-term survival advantage compared to patients receiving cemented or an uncemented THR," said Dr. Adrian Kendal of the National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit at the University of Oxford, England.

"Our findings were robust after adjustment for known confounders," Dr. Kendal said at the British Society for Rheumatology annual conference. Propensity matching was used in the trial, which took age, gender, comorbidity, rurality, and social deprivation into account.

For the study, data from the English Hospital Episode Statistics database were obtained and linked to Office for National Statistics mortality records for all adults (over age 18) undergoing elective primary hip replacement for osteoarthritis in National Health Service hospitals in England and Wales between April 1999 and March 2012.

After propensity score matching, there were 91,633 procedures performed, of which 12,580 were MoMR, 37,740 were cemented THR, and 41,312 were uncemented THR.

In response to a comment that perhaps people opting for MoMR were more likely to be younger, more active, and hence more likely to exercise, Dr. Kendal conceded that other factors might exist that could have affected survival.

Speculating about why there might be such a difference in survival, he said: "I personally don’t think it’s just the use of cement, because that doesn’t explain the group that received an uncemented total hip replacement."

He added that the way the femur is prepared during THR might be important, regardless of whether or not cement is used. The known risk of thrombotic consequences also could affect survival. In addition, health care inequality might be important, as resurfacing procedures are less common than THR, perhaps because of the lack of specialized centers or dedicated teams.

Commenting on the findings after their presentation, consultant rheumatologist Dr. Alex MacGregor, of the University of East Anglia, Norwich, England, noted that similar data were published on this topic last year (BMJ 2012;344:e3319), but the results had proved somewhat controversial as the authors had a conflict of interest in favor of hip resurfacing.

Dr. MacGregor, who is a member of the National Joint Registry Steering Committee, has been involved in a subsequent reanalysis of the paper’s findings and said that the results will be made public later in the year.

"One of my concerns [with this study] is the use of the 10-year mortality endpoint. If these resurfacing procedures are saving lives, then you would expect to see a survival benefit sooner, say at 90 days," Dr. MacGregor said.

Dr. Kendal responded that they tried to account for this, but the answer will need to come from a properly organized, randomized controlled trial.

"We don’t have a conflict of interest here. If anything, we were perhaps looking for the opposite effect; we were expecting to see an increased mortality rate in the resurfacing group," Dr. Kendal said. "That was not the case as it turned out, so I am reasonably confident that our data support the findings of that BMJ article."

Dr. Kendal and Dr. MacGregor reported no conflicts of interest.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Combinations of conventional antirheumatic drugs are as clinically effective as more expensive biologic agents in managing patients with active, established rheumatoid arthritis, randomized trial data suggest.

Health Assessment Questionnaire (HAQ) scores at 12 months were lower in patients given conventional disease-modifying antirheumatic drugs (cDMARDs) as compared to a tumor necrosis factor inhibitor (TNFi) after failure of methotrexate and at least one other DMARD (1.35 vs. 1.60, P = .046).

Nevertheless, the two approaches were "clinically equivalent," said trial investigator Dr. David L. Scott at the annual meeting of the British Society for Rheumatology.

"In patients with methotrexate-resistant rheumatoid arthritis [RA], giving the cDMARD intensive therapy and starting off with a TNFi achieves similar outcomes, causes comparable harms, but the cDMARDs cost less," said Dr. Scott, who is professor of clinical rheumatology at King’s College London.

These data, from the TACIT (Tumor Necrosis Factor Inhibitors or Conventional Drugs in Rheumatoid Arthritis) trial, suggest that combination DMARD therapy could be an alternative approach for patients with established RA, reserving anti-TNF agents for those who fail intensive DMARD treatment.

Dr. Scott noted that the findings might warrant a change in practice in the United Kingdom, where anti-TNFs are currently recommended as the next choice in patients who do not respond to treatment with two individual DMARDs, one of which must be methotrexate. Such an approach is based on evidence from placebo-controlled, rather than head-to-head, trials, however, and such a "one size fits all" approach perhaps needs reevaluation.

The TACIT trial was conducted in 24 centers in the United Kingdom and involved 205 patients who had RA for a median duration of 4 years. The aim of the trial was to directly compare two different treatment strategies: a TNFi (infliximab, etanercept, or adalimumab) given to patients after failing methotrexate and a subsequent DMARD versus methotrexate followed by combination cDMARDs and then a TNFi.

Combinations of cDMARDs used in the trial included triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine; other methotrexate combinations (methotrexate-cyclosporin, methotrexate-leflunomide, and methotrexate-gold); and one sulfasalazine combination (sulfasalazine-leflunomide).

At 12 months’ follow-up, there was no significant difference between the treatment strategies in terms of quality of life measured using the EuroQol instrument, radiographic progression assessed using Larsen scores, or disease activity assessed via monthly Disease Activity Score-28 (DAS28).

The mean change in DAS28 score was initially greater in TNFi-treated patients (–2.07 vs. –1.45, P = .007) at 6 months, Dr. Scott said, but this difference was lost with longer follow-up. "This simply shows that, as we’ve always known, TNFi’s act rapidly and DMARDs are slow acting," he observed.

Economic analysis showed a clear advantage for the use of cDMARDs over anti-TNF agents, with an annual estimated saving of health and social care costs of £5,552 (U.S.$8,400) per patient. Taking lost productivity and social security payments into account did not change the findings.

Safety is a concern of using multiple cDMARDs, particularly older combinations, but the TACIT data showed that there were a comparable number of adverse reactions. The total number of events was 635 for cDMARDs and 465 in the TNFi group. Of these, there were more digestive adverse events in the cDMARD arm than in the TNFi group (148 vs. 60), but more infections in the anti-TNF-treated patients than in the cDMARD group (54 vs. 30).

Serious adverse events were noted in 10 and 18 of cDMARD- and TNFi-treated patients, respectively, with 10 and 6 patients in each group withdrawing as a result of experiencing a side effect. There was one death, due to pneumonia and multiple organ failure, in the anti-TNF arm.

"We should think about the treatment strategy in terms of intensive DMARDs first of all and then moving onto biologics," Dr. Scott said. Remission needs to be a target of treatment, he added, although this is rarely achieved by either strategy. Remission rates at 12 months seen in TACIT are comparable to rates reported from several registries, including CORRONA (Consortium of Rheumatology Researchers of North America) in the United States, DANBIO in Denmark, RABBIT in Germany, and BSRBR-RA (British Society for Rheumatology Biologics Register-Rheumatoid Arthritis) in the United Kingdom.

Dr. Scott concluded by noting that there are three unresolved questions. First, it is not clear what the best combination of cDMARDs is; second, the optimum way to use biologics is currently unknown; and third, it is not clear how to convert patients with intermediate disease activity into patients who may achieve clinical remission.

The TACIT trial was supported by a Health Technology Assessment grant from the U.K. National Institute for Health Research. Dr. Scott and his coinvestigators reported having no conflicts of interest.

BIRMINGHAM, ENGLAND – Combinations of conventional antirheumatic drugs are as clinically effective as more expensive biologic agents in managing patients with active, established rheumatoid arthritis, randomized trial data suggest.

Health Assessment Questionnaire (HAQ) scores at 12 months were lower in patients given conventional disease-modifying antirheumatic drugs (cDMARDs) as compared to a tumor necrosis factor inhibitor (TNFi) after failure of methotrexate and at least one other DMARD (1.35 vs. 1.60, P = .046).

Nevertheless, the two approaches were "clinically equivalent," said trial investigator Dr. David L. Scott at the annual meeting of the British Society for Rheumatology.

"In patients with methotrexate-resistant rheumatoid arthritis [RA], giving the cDMARD intensive therapy and starting off with a TNFi achieves similar outcomes, causes comparable harms, but the cDMARDs cost less," said Dr. Scott, who is professor of clinical rheumatology at King’s College London.

These data, from the TACIT (Tumor Necrosis Factor Inhibitors or Conventional Drugs in Rheumatoid Arthritis) trial, suggest that combination DMARD therapy could be an alternative approach for patients with established RA, reserving anti-TNF agents for those who fail intensive DMARD treatment.

Dr. Scott noted that the findings might warrant a change in practice in the United Kingdom, where anti-TNFs are currently recommended as the next choice in patients who do not respond to treatment with two individual DMARDs, one of which must be methotrexate. Such an approach is based on evidence from placebo-controlled, rather than head-to-head, trials, however, and such a "one size fits all" approach perhaps needs reevaluation.

The TACIT trial was conducted in 24 centers in the United Kingdom and involved 205 patients who had RA for a median duration of 4 years. The aim of the trial was to directly compare two different treatment strategies: a TNFi (infliximab, etanercept, or adalimumab) given to patients after failing methotrexate and a subsequent DMARD versus methotrexate followed by combination cDMARDs and then a TNFi.

Combinations of cDMARDs used in the trial included triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine; other methotrexate combinations (methotrexate-cyclosporin, methotrexate-leflunomide, and methotrexate-gold); and one sulfasalazine combination (sulfasalazine-leflunomide).

At 12 months’ follow-up, there was no significant difference between the treatment strategies in terms of quality of life measured using the EuroQol instrument, radiographic progression assessed using Larsen scores, or disease activity assessed via monthly Disease Activity Score-28 (DAS28).

The mean change in DAS28 score was initially greater in TNFi-treated patients (–2.07 vs. –1.45, P = .007) at 6 months, Dr. Scott said, but this difference was lost with longer follow-up. "This simply shows that, as we’ve always known, TNFi’s act rapidly and DMARDs are slow acting," he observed.

Economic analysis showed a clear advantage for the use of cDMARDs over anti-TNF agents, with an annual estimated saving of health and social care costs of £5,552 (U.S.$8,400) per patient. Taking lost productivity and social security payments into account did not change the findings.

Safety is a concern of using multiple cDMARDs, particularly older combinations, but the TACIT data showed that there were a comparable number of adverse reactions. The total number of events was 635 for cDMARDs and 465 in the TNFi group. Of these, there were more digestive adverse events in the cDMARD arm than in the TNFi group (148 vs. 60), but more infections in the anti-TNF-treated patients than in the cDMARD group (54 vs. 30).

Serious adverse events were noted in 10 and 18 of cDMARD- and TNFi-treated patients, respectively, with 10 and 6 patients in each group withdrawing as a result of experiencing a side effect. There was one death, due to pneumonia and multiple organ failure, in the anti-TNF arm.

"We should think about the treatment strategy in terms of intensive DMARDs first of all and then moving onto biologics," Dr. Scott said. Remission needs to be a target of treatment, he added, although this is rarely achieved by either strategy. Remission rates at 12 months seen in TACIT are comparable to rates reported from several registries, including CORRONA (Consortium of Rheumatology Researchers of North America) in the United States, DANBIO in Denmark, RABBIT in Germany, and BSRBR-RA (British Society for Rheumatology Biologics Register-Rheumatoid Arthritis) in the United Kingdom.

Dr. Scott concluded by noting that there are three unresolved questions. First, it is not clear what the best combination of cDMARDs is; second, the optimum way to use biologics is currently unknown; and third, it is not clear how to convert patients with intermediate disease activity into patients who may achieve clinical remission.

The TACIT trial was supported by a Health Technology Assessment grant from the U.K. National Institute for Health Research. Dr. Scott and his coinvestigators reported having no conflicts of interest.

BIRMINGHAM, ENGLAND – Combinations of conventional antirheumatic drugs are as clinically effective as more expensive biologic agents in managing patients with active, established rheumatoid arthritis, randomized trial data suggest.

Health Assessment Questionnaire (HAQ) scores at 12 months were lower in patients given conventional disease-modifying antirheumatic drugs (cDMARDs) as compared to a tumor necrosis factor inhibitor (TNFi) after failure of methotrexate and at least one other DMARD (1.35 vs. 1.60, P = .046).

Nevertheless, the two approaches were "clinically equivalent," said trial investigator Dr. David L. Scott at the annual meeting of the British Society for Rheumatology.

"In patients with methotrexate-resistant rheumatoid arthritis [RA], giving the cDMARD intensive therapy and starting off with a TNFi achieves similar outcomes, causes comparable harms, but the cDMARDs cost less," said Dr. Scott, who is professor of clinical rheumatology at King’s College London.

These data, from the TACIT (Tumor Necrosis Factor Inhibitors or Conventional Drugs in Rheumatoid Arthritis) trial, suggest that combination DMARD therapy could be an alternative approach for patients with established RA, reserving anti-TNF agents for those who fail intensive DMARD treatment.

Dr. Scott noted that the findings might warrant a change in practice in the United Kingdom, where anti-TNFs are currently recommended as the next choice in patients who do not respond to treatment with two individual DMARDs, one of which must be methotrexate. Such an approach is based on evidence from placebo-controlled, rather than head-to-head, trials, however, and such a "one size fits all" approach perhaps needs reevaluation.

The TACIT trial was conducted in 24 centers in the United Kingdom and involved 205 patients who had RA for a median duration of 4 years. The aim of the trial was to directly compare two different treatment strategies: a TNFi (infliximab, etanercept, or adalimumab) given to patients after failing methotrexate and a subsequent DMARD versus methotrexate followed by combination cDMARDs and then a TNFi.

Combinations of cDMARDs used in the trial included triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine; other methotrexate combinations (methotrexate-cyclosporin, methotrexate-leflunomide, and methotrexate-gold); and one sulfasalazine combination (sulfasalazine-leflunomide).

At 12 months’ follow-up, there was no significant difference between the treatment strategies in terms of quality of life measured using the EuroQol instrument, radiographic progression assessed using Larsen scores, or disease activity assessed via monthly Disease Activity Score-28 (DAS28).

The mean change in DAS28 score was initially greater in TNFi-treated patients (–2.07 vs. –1.45, P = .007) at 6 months, Dr. Scott said, but this difference was lost with longer follow-up. "This simply shows that, as we’ve always known, TNFi’s act rapidly and DMARDs are slow acting," he observed.

Economic analysis showed a clear advantage for the use of cDMARDs over anti-TNF agents, with an annual estimated saving of health and social care costs of £5,552 (U.S.$8,400) per patient. Taking lost productivity and social security payments into account did not change the findings.

Safety is a concern of using multiple cDMARDs, particularly older combinations, but the TACIT data showed that there were a comparable number of adverse reactions. The total number of events was 635 for cDMARDs and 465 in the TNFi group. Of these, there were more digestive adverse events in the cDMARD arm than in the TNFi group (148 vs. 60), but more infections in the anti-TNF-treated patients than in the cDMARD group (54 vs. 30).

Serious adverse events were noted in 10 and 18 of cDMARD- and TNFi-treated patients, respectively, with 10 and 6 patients in each group withdrawing as a result of experiencing a side effect. There was one death, due to pneumonia and multiple organ failure, in the anti-TNF arm.

"We should think about the treatment strategy in terms of intensive DMARDs first of all and then moving onto biologics," Dr. Scott said. Remission needs to be a target of treatment, he added, although this is rarely achieved by either strategy. Remission rates at 12 months seen in TACIT are comparable to rates reported from several registries, including CORRONA (Consortium of Rheumatology Researchers of North America) in the United States, DANBIO in Denmark, RABBIT in Germany, and BSRBR-RA (British Society for Rheumatology Biologics Register-Rheumatoid Arthritis) in the United Kingdom.

Dr. Scott concluded by noting that there are three unresolved questions. First, it is not clear what the best combination of cDMARDs is; second, the optimum way to use biologics is currently unknown; and third, it is not clear how to convert patients with intermediate disease activity into patients who may achieve clinical remission.

The TACIT trial was supported by a Health Technology Assessment grant from the U.K. National Institute for Health Research. Dr. Scott and his coinvestigators reported having no conflicts of interest.