Rheumatoid Arthritis

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.

These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.

Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."

PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.

In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.

Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).

No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.

Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.

Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

VICTORIA, B.C. – Patients with rheumatoid arthritis who also have common comorbidities are at increased risk for infection when starting treatment with at least one class of biologic agents, based on the findings of a cohort study.

Investigators led by Dr. Joanne Homik, director of the division of rheumatology at the University of Alberta in Edmonton, studied 1,086 patients with rheumatoid arthritis (RA) who were initiating treatment, in most cases with a biologic agent targeting tumor necrosis factor (TNF).

In adjusted analyses, patients had more than triple the risk of a serious infection, defined as one requiring hospitalization, if they had anemia, according to data from the as-yet unpublished study. In other findings, patients were 97% more likely to develop an infection if they had lung disease and 39% more likely if they had heart disease.

"The anemia variable has an unclear relationship, but we are looking into that further. Our theory is that with lung disease, that has some biologic plausibility since bronchitis and pneumonia have prominence in our list of infections seen in this cohort," Dr. Homik commented at the annual meeting of the Canadian Rheumatology Association.

The incidence density of serious infection was 1.67 cases per 100 patient-years, about half that found in some other cohorts. "One of the things we thought of when trying to explain why our serious infection risk is so low is that health care restructuring in Alberta in the mid-90s resulted in bed closures," she explained. "So hospitalizations were reduced overall, and many patients who ... could be considered seriously ill are not admitted any longer, and it can be a bit more challenging to [identify] those serious infections."

The study occurred shortly after anti-TNF agents first became available, so the patients receiving them usually had the most severe, long-standing RA, Dr. Homik noted. Over time, as the demographic of the database changes to include more patients within the first 5 years of their RA, outcomes may differ and predictors may differ as well.

The risk of any infection among patients starting anti-TNF agents did not differ from that among patients starting the disease-modifying antirheumatic drug (DMARD) leflunomide instead. However, leflunomide confers a higher infection risk than some other DMARDs, she noted.

The investigators used registry data to study a cohort of all 943 patients with RA in Alberta who started a first anti-TNF agent between January 2004 and March 2009, and also studied a comparison cohort of 143 patients who started leflunomide (Arava). The patients completed the self-administered comorbidity questionnaire at baseline and were monitored prospectively for outcomes and adverse events. Their average age was 54 years, and 70% were female.

With a mean follow-up of 2.3 years, 70% of patients developed an infection as ascertained from physician claims data or self-report; the most common were bronchitis, cellulitis, and sinusitis. Nearly 4% of patients developed a serious infection; the most common were pneumonia, cellulitis, septicemia, and septic arthritis.

In the first multivariate analysis, patients had an elevated risk of infection if they had heart disease (hazard ratio, 1.39) or lung disease (1.97), used steroids (1.2), or currently smoked (1.24). Their risk was decreased risk if they were male (HR, 0.78). When analysis was restricted to the subset who started an anti-TNF agent, infection risk was increased for those with lung disease (2.02) and decreased for men (0.80).

In the second multivariate analysis, patients had an elevated risk of serious infection if they had anemia (HR, 3.26) or used steroids (3.21), and a decreased risk if they had more than a secondary education (0.33). In the subset who started an anti-TNF agent, risk was increased for patients who had anemia (HR, 3.7) or used steroids (3.5), and decreased for those having more than a secondary education (0.3).

The risks of infection and serious infection did not differ across subgroups when patients were stratified according to whether they stayed on their first treatment or switched from one kind of DMARD to their first anti-TNF agent (or from one anti-TNF agent to another), Dr. Homik reported.

"In the cohort of patients on their first anti-TNF agent, the specific anti-TNF agent used did not predict risk of infection," she noted.

Dr. Homik disclosed that she serves as a consultant to Abbott, Amgen, Pfizer, and Roche. The Alberta Biologics Registry has received unrestricted grant support from Abbott, Amgen, Bristol-Myers Squibb, Merck/Jansson, and Pfizer.

PALM SPRINGS, CALIF. – The degree of sacroiliac joint pain relief provided by intra-articular steroid injection of the sacroiliac joint did not predict the duration of pain relief from subsequent radiofrequency ablation of the lateral branches that innervate the sacroiliac joint, judging from findings from a retrospective study of 80 patients.

Based on these results, patients who get only 25%-49% relief of pain from steroid injection of the sacroiliac joint (SISI) should not be disqualified from undergoing radiofrequency ablation of the lateral branches, Dr. Jianguo Cheng and his associates suggested in an award-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

The study retrospectively collected data on 87 patients undergoing radiofrequency ablation of the lateral branches who’d had a preoperative SISI between January 2006 and June 2009 at The Cleveland Clinic. The seven patients who were missing follow-up data were excluded from the final analysis.

In all, 60 of the 80 patients in the analysis reported at least 50% pain relief as a result of SISI (75%) and 20 patients reported less than 50% pain relief (25%). After radiofrequency ablation of the lateral branches, approximately 50% of all patients reported at least a 50% reduction in pain. The degree of pain relief from radiofrequency ablation did not differ significantly at follow-up visits 1, 3, 6, and 12 months between patients who had experienced 25%-49% pain relief after SISI and patients who reported 50% or greater pain relief after SISI, said Dr. Cheng, who is professor of anesthesiology and program director of pain medicine fellowship program of Cleveland Clinic Foundation.

The analysis adjusted for the effects of potential confounders. Patients who had experienced less than 50% pain relief after SISI were significantly younger than those with at least 50% pain relief after SISI (a mean of 52 years vs. 59 years) and significantly less likely to have had gradual onset of their chronic back pain (60% vs. 82%) and more likely to have had pain with extension or axial rotation (80% vs. 52%). Other characteristics did not differ between groups.

Although the efficacy of radiofrequency ablation of the lateral branches at 3 months was comparable to reports in the literature, the efficacy after 6 months was lower in the study compared with previous reports. Approximately 40% of patients in the study had at least a 50% reduction in pain 6 months after radiofrequency ablation compared with 52%-57% in published reports, Dr. Cheng said. This difference may be due to the older age of patients in the current study compared with previous ones (58 vs. 52 years on average), a higher rate of previous spine surgery (30% vs. 21%), and greater likelihood of multiple pain complaints and opioid use in the current cohort (70% vs. 46%), he suggested.

The current study is larger than most previous ones but is limited by its retrospective design, Dr. Cheng said.

In general, 16%-30% of cases of chronic lower back pain can be attributed to sacroiliac joint pain. Radiofrequency ablation of the lateral branches has emerged as a promising modality in recent years while other treatment modalities have provided mixed and often disappointing results, including pharmacotherapy, viscosupplementation, prolotherapy, chiropractic manipulation, intra-articular injections, and surgical fixation, he said. The findings of the current study should help inform pain interventionists in deciding who is a candidate for radiofrequency ablation.

Dr. Cheng reported having no financial disclosures.

PALM SPRINGS, CALIF. – The degree of sacroiliac joint pain relief provided by intra-articular steroid injection of the sacroiliac joint did not predict the duration of pain relief from subsequent radiofrequency ablation of the lateral branches that innervate the sacroiliac joint, judging from findings from a retrospective study of 80 patients.

Based on these results, patients who get only 25%-49% relief of pain from steroid injection of the sacroiliac joint (SISI) should not be disqualified from undergoing radiofrequency ablation of the lateral branches, Dr. Jianguo Cheng and his associates suggested in an award-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

The study retrospectively collected data on 87 patients undergoing radiofrequency ablation of the lateral branches who’d had a preoperative SISI between January 2006 and June 2009 at The Cleveland Clinic. The seven patients who were missing follow-up data were excluded from the final analysis.

In all, 60 of the 80 patients in the analysis reported at least 50% pain relief as a result of SISI (75%) and 20 patients reported less than 50% pain relief (25%). After radiofrequency ablation of the lateral branches, approximately 50% of all patients reported at least a 50% reduction in pain. The degree of pain relief from radiofrequency ablation did not differ significantly at follow-up visits 1, 3, 6, and 12 months between patients who had experienced 25%-49% pain relief after SISI and patients who reported 50% or greater pain relief after SISI, said Dr. Cheng, who is professor of anesthesiology and program director of pain medicine fellowship program of Cleveland Clinic Foundation.

The analysis adjusted for the effects of potential confounders. Patients who had experienced less than 50% pain relief after SISI were significantly younger than those with at least 50% pain relief after SISI (a mean of 52 years vs. 59 years) and significantly less likely to have had gradual onset of their chronic back pain (60% vs. 82%) and more likely to have had pain with extension or axial rotation (80% vs. 52%). Other characteristics did not differ between groups.

Although the efficacy of radiofrequency ablation of the lateral branches at 3 months was comparable to reports in the literature, the efficacy after 6 months was lower in the study compared with previous reports. Approximately 40% of patients in the study had at least a 50% reduction in pain 6 months after radiofrequency ablation compared with 52%-57% in published reports, Dr. Cheng said. This difference may be due to the older age of patients in the current study compared with previous ones (58 vs. 52 years on average), a higher rate of previous spine surgery (30% vs. 21%), and greater likelihood of multiple pain complaints and opioid use in the current cohort (70% vs. 46%), he suggested.

The current study is larger than most previous ones but is limited by its retrospective design, Dr. Cheng said.

In general, 16%-30% of cases of chronic lower back pain can be attributed to sacroiliac joint pain. Radiofrequency ablation of the lateral branches has emerged as a promising modality in recent years while other treatment modalities have provided mixed and often disappointing results, including pharmacotherapy, viscosupplementation, prolotherapy, chiropractic manipulation, intra-articular injections, and surgical fixation, he said. The findings of the current study should help inform pain interventionists in deciding who is a candidate for radiofrequency ablation.

Dr. Cheng reported having no financial disclosures.

PALM SPRINGS, CALIF. – The degree of sacroiliac joint pain relief provided by intra-articular steroid injection of the sacroiliac joint did not predict the duration of pain relief from subsequent radiofrequency ablation of the lateral branches that innervate the sacroiliac joint, judging from findings from a retrospective study of 80 patients.

Based on these results, patients who get only 25%-49% relief of pain from steroid injection of the sacroiliac joint (SISI) should not be disqualified from undergoing radiofrequency ablation of the lateral branches, Dr. Jianguo Cheng and his associates suggested in an award-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

The study retrospectively collected data on 87 patients undergoing radiofrequency ablation of the lateral branches who’d had a preoperative SISI between January 2006 and June 2009 at The Cleveland Clinic. The seven patients who were missing follow-up data were excluded from the final analysis.

In all, 60 of the 80 patients in the analysis reported at least 50% pain relief as a result of SISI (75%) and 20 patients reported less than 50% pain relief (25%). After radiofrequency ablation of the lateral branches, approximately 50% of all patients reported at least a 50% reduction in pain. The degree of pain relief from radiofrequency ablation did not differ significantly at follow-up visits 1, 3, 6, and 12 months between patients who had experienced 25%-49% pain relief after SISI and patients who reported 50% or greater pain relief after SISI, said Dr. Cheng, who is professor of anesthesiology and program director of pain medicine fellowship program of Cleveland Clinic Foundation.

The analysis adjusted for the effects of potential confounders. Patients who had experienced less than 50% pain relief after SISI were significantly younger than those with at least 50% pain relief after SISI (a mean of 52 years vs. 59 years) and significantly less likely to have had gradual onset of their chronic back pain (60% vs. 82%) and more likely to have had pain with extension or axial rotation (80% vs. 52%). Other characteristics did not differ between groups.

Although the efficacy of radiofrequency ablation of the lateral branches at 3 months was comparable to reports in the literature, the efficacy after 6 months was lower in the study compared with previous reports. Approximately 40% of patients in the study had at least a 50% reduction in pain 6 months after radiofrequency ablation compared with 52%-57% in published reports, Dr. Cheng said. This difference may be due to the older age of patients in the current study compared with previous ones (58 vs. 52 years on average), a higher rate of previous spine surgery (30% vs. 21%), and greater likelihood of multiple pain complaints and opioid use in the current cohort (70% vs. 46%), he suggested.

The current study is larger than most previous ones but is limited by its retrospective design, Dr. Cheng said.

In general, 16%-30% of cases of chronic lower back pain can be attributed to sacroiliac joint pain. Radiofrequency ablation of the lateral branches has emerged as a promising modality in recent years while other treatment modalities have provided mixed and often disappointing results, including pharmacotherapy, viscosupplementation, prolotherapy, chiropractic manipulation, intra-articular injections, and surgical fixation, he said. The findings of the current study should help inform pain interventionists in deciding who is a candidate for radiofrequency ablation.

Dr. Cheng reported having no financial disclosures.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Suboptimal vitamin D levels may play a role in the pathogenesis of inflammatory arthritis but not in its subsequent clinical course, judging from the findings of a study involving 264 adult patients with early disease.

Fully 77% of patients had vitamin D deficiency or insufficiency at baseline, reported lead investigator Dr. Carol A. Hitchon at the annual meeting of Canadian Rheumatology Association. But in findings that contrasted those of some earlier studies, levels were not significantly associated with disease activity at that time or with achievement of remission 1 year later.

The study also found that vitamin D levels did not correlate with levels of immunoglobulin directed against common pathogens implicated in the development of rheumatoid arthritis.

"It’s possible that vitamin D levels may not be that important in terms of clinical activity and that vitamin D status may be more important in predisposing to rheumatoid arthritis," Dr. Hitchon commented. "I don’t think vitamin D is the only answer. And I think it’s not just the level, it is probably other elements of the vitamin D pathway that might be important, in terms of how they may regulate autoimmune processes."

A session attendee wondered whether patients with inflammatory arthritis may simply have lower levels of this vitamin because they go out in the sun less.

That is a possible explanation, acknowledged Dr. Hitchon of the arthritis center at the University of Manitoba in Winnipeg. "We are hoping to measure vitamin D levels in a population that generally has more sun exposure based on where they reside, and that may give us some correlation," she added.

Accumulating data suggest that vitamin D plays a role in maintaining both tolerance and immunity to pathogens. Thus, the investigators hypothesized, "if you are deficient in vitamin D, it may lead to a break of self-tolerance and the development of autoimmunity. Similarly, deficient vitamin D can impair or alter the initial response to pathogens, leading to increased microbial load, which can also increase or affect autoimmunity," Dr. Hitchon said.

She and her colleagues studied patients from the Manitoba Early Arthritis Cohort. All of the patients had had symptoms of inflammatory arthritis for no more than 1 year, and had at least one swollen joint.

The severity of their arthritis was assessed with the DAS28-CRP (28-joint count Disease Activity Score, C-reactive protein). Circulating levels of 25-hydroxyvitamin D and antibodies to Escherichia coli and Proteus mirabilis – both of which have been implicated in rheumatoid arthritis – were measured in serum collected before the start of treatment.

The average age of the patients studied was 48 years, and 76% were women. Overall, 60% were rheumatoid factor–positive, and 49% were positive for CCP2 (cyclic citrullinated peptide, second-generation assay). Their mean DAS28-CRP score was 3.99.

Results showed that 16% of patients had vitamin D deficiency and 61% had vitamin D insufficiency, while just 23% had optimal levels. Smokers had significantly lower levels than did nonsmokers.

There was no association at baseline between vitamin D levels and rheumatoid factor or CCP2 levels, DAS28-CRP score, or several other measures of disease activity, reported Dr. Hitchon, who disclosed no relevant conflicts of interest.

In adjusted analyses, vitamin D levels were not significantly associated with DAS28-CRP score at baseline or with achievement of remission 1 year later. "As has been previously shown, the major predictor of 1-year outcome was the baseline DAS score," she noted.

During the study, 20% of patients had an improvement in their vitamin D levels, moving to a higher category, whereas 12% of patients had a worsening, moving to a lower category. "This is without any formal protocol or plan to supplement vitamin D," Dr. Hitchon pointed out.

There was also no significant correlation between vitamin D levels and levels of immunoglobulins –whether IgA, IgM, or IgG – to E. coli or P. mirabilis.

Dr. Hitchon disclosed no relevant conflicts of interest.

Musculoskeletal ultrasound is an efficient, noninvasive method for evaluating inflammatory and destructive changes in bone, cartilage, tendons, ligaments, and surrounding soft tissue of patients with psoriatic arthritis. The bedside technology allows the monitoring of all peripheral joints as frequently as needed in the management of early, active disease. Power Doppler ultrasound, in particular, can estimate increases in synovium, tendon sheaths, bursae, and enthesis. Thus it provides invaluable insight into disease status and progression, according to Dr. Marwin Gutierrez, assistant professor of rheumatology at Università Politecnica delle Marche in Ancona. Italy.

Despite its value, "[ultrasound] imaging is not firmly established in the assessment of treatment efficacy and monitoring of patient outcome in daily practice," said Dr. Gutierrez. And although joint, tendon, enthesis, skin, and nail involvement has been widely described by the different subset criteria as aspects to consider in psoriatic arthritis, "ultrasound research in the disease has relatively lagged behind that of rheumatoid arthritis [RA], with scarce validated imaging outcome measures," he said.

In this month’s column, Dr. Gutierrez discusses both the role of ultrasound imaging in the assessment of psoriatic arthritis (PsA) and his group’s development of a preliminary power Doppler ultrasound composite score for monitoring treatment of the disease (Rheumatology 2012 Feb. 29 [doi:10.1093/rheumatology/kes014]).

Question: What tools are currently being used for the global assessment of PsA?

Dr. Gutierrez: There are a variety of clinical instruments for measuring disease activity and treatment response in patients with PsA, including the Disease Activity Index for PsA (DAPSA), the PsA Response Criteria (PsARC), and the Disease Activity Score using 28 joint counts (DAS28), which was originally developed for patients with RA. The main weakness of the majority of these tools is that they are focused only on joint involvement and do not include measures of other key PsA targets, such as tendons, skin, and nails. Recently, the Composite Psoriatic Disease Activity Index (CPDAI) has been proposed, which includes multiple clinical domains – joints, tendons, and the spine – in its assessment. This tool provides more comprehensive information regarding disease activity, but it is limited by the absence of imaging findings, which offer a more objective measure of the global condition of the PsA patient.

Because a composite ultrasound score does not exist at present for PsA, we tested the possibility of using power Doppler ultrasound as a global measure of the inflammatory process to detect perfusion changes induced by tumor necrosis factor (TNF)-alpha antagonist, which have been shown in recent studies to be effective in improving functional outcomes and to arrest disease progression.

Question: How are the existing tools and measures insufficient? How would the power Doppler ultrasound composite score that your group has developed fill in the gaps?

Dr. Gutierrez: PsA is a chronic inflammatory disease. Its heterogeneity is such that the term "psoriatic disease" has been recently suggested to encompass the involvement at different tissue levels, including joints, tendons, enthesis, skin, and nails. Due to the high variability in the clinical course both within one patient and between patients, as well as the variability in the outcomes of PsA, no single measure can provide accurate information regarding disease activity and responsiveness in these patients.

The main disadvantage of the most commonly used clinical measures in the assessment of PsA is that they do not provide information on the real-time activity of the psoriatic disease. Rather, they provide information confined to the assessment of single domains separately. The alternative is individual evaluation of all targets. However, such an approach is associated with methodological and statistical problems, especially when these targets are employed as end points in clinical trials.

High-frequency ultrasound can detect not only structural abnormalities but also minimal blood flow changes at the superficial soft tissue level, making it a great tool for the global assessment of disease activity in psoriatic arthritis, in which persistently active disease plays a major role in causing anatomical damage and physical functional disability. Furthermore, the ability to measure global disease activity over time is important in assessing treatment efficacy in clinical trials and monitoring the patient’s course in daily care.

Additionally, pooling individual domains of disease activity into a composite ultrasound score offers a picture of disease activity along a continuous scale, and facilitates more consistency in the assessment and communication of disease activity and treatment response in research settings and clinical practice.

Question: Of the various imaging technologies, why is ultrasound the modality of choice for this application?

Dr. Gutierrez: Early detection and careful characterization of the inflammatory process in PsA play a key role in both diagnostic and therapeutic procedures. Ultrasound technology has the essential qualities to satisfy these fundamental necessities, including high- and variable-frequency probes and very sensitive power Doppler. These capabilities permit the study of structural changes with a resolution power of 0.1 mm and the sensitive detection of blood flow even in the small vessels of superficial tissues.

In addition to being sensitive enough to assess anatomical changes, disease activity, and therapeutic efficacy, ultrasound is safe, noninvasive, patient friendly, free of ionizing radiation, and less expensive than other imaging methods. It also allows multiple target assessment in real time without the need for external referral. Compared with conventional radiography, magnetic resonance imaging (MRI), or computed tomography (CT), power Doppler ultrasound can simultaneously reflect a change in inflammatory activity by accurately measuring blood flow changes and assess the progression of anatomical damage.

Question: What are the strengths and weaknesses of the preliminary power Doppler ultrasound composite score?

Dr. Gutierrez: Our preliminary composite score, called Five Targets Power Doppler for Psoriatic Disease (5TPD), includes the assessment of changes in joints, tendons with synovial sheath, entheses, skin, and nails. It represents a feasible, reliable, and comprehensive approach for multitarget monitoring of PsA.

The score is based on the simple arithmetic sum of the scores regarding the five clinical targets. Power Doppler for each target is graded from 0 to 3 on the basis of the semiquantitative scoring systems previously suggested. The maximum total score of 5TPDis 15. In our study, the instrument was found to possess both face and content validity, and it exhibited good responsiveness. By documenting these key measurement properties, we have shown that the 5TPD is a useful instrument for the assessment of disease activity and responsiveness in PsA patients and is, therefore, potentially applicable in standard clinical care, observational studies, and clinical trials.

The 5PTD is feasible and easy to perform in the hands of expert sonographers. The baseline assessment takes an average of 10.5 minutes. The follow-up complete examination, including calculating the score, averages no more than 7 minutes, which makes it quite practical in busy clinical settings.

The main limitation of the score currently is that it was tested in a small cohort of patients, which does not allow for an accurate evaluation in terms of the sensitivity and specificity needed to support our results more strongly. Also, we need to consider the ceiling effect. For example, high composite ultrasound scores denote the involvement of multiple target areas of psoriatic disease, and they can be shared by patients with relevant differences in terms of the extent of the inflammatory involvement at each specific target area. In other words, a severe inflammation of a single joint showing a power Doppler grade of 3 gives the maximum contribution to the final score; an equally severe inflammation in terms of power Doppler appearance, but polyarticular involvement, cannot provide more than 3 and thus would be easily underestimated. We are currently developing steps aimed at defining a linear cutoff value point for any single domain of 5TPD to resolve this aspect.

It is important to remember that this composite score was designed to monitor PsA disease activity in daily practice after a complete clinical examination, and not to replace other well-established and accepted ultrasound assessments.

Question: What is next for the 5TPD?

Dr. Gutierrez: Investigations are ongoing to assess the advantages and limitations of the formula in wider cohorts of patients. The composite score needs further development and concurrent and discriminate validation through randomized controlled trials and longitudinal observational studies. The tool is currently being evaluated prospectively as part of a larger multicenter study, as well as in a study comparing it with the CPDAI for the assessment of disease activity and responsiveness.

–Interview by Diana Mahoney

Dr. Gutierrez is scientific director of the Pan-American League of Associations for Rheumatology (PANLAR) Ultrasound Group. He reported having no financial conflicts of interest.

Musculoskeletal ultrasound is an efficient, noninvasive method for evaluating inflammatory and destructive changes in bone, cartilage, tendons, ligaments, and surrounding soft tissue of patients with psoriatic arthritis. The bedside technology allows the monitoring of all peripheral joints as frequently as needed in the management of early, active disease. Power Doppler ultrasound, in particular, can estimate increases in synovium, tendon sheaths, bursae, and enthesis. Thus it provides invaluable insight into disease status and progression, according to Dr. Marwin Gutierrez, assistant professor of rheumatology at Università Politecnica delle Marche in Ancona. Italy.

Despite its value, "[ultrasound] imaging is not firmly established in the assessment of treatment efficacy and monitoring of patient outcome in daily practice," said Dr. Gutierrez. And although joint, tendon, enthesis, skin, and nail involvement has been widely described by the different subset criteria as aspects to consider in psoriatic arthritis, "ultrasound research in the disease has relatively lagged behind that of rheumatoid arthritis [RA], with scarce validated imaging outcome measures," he said.

In this month’s column, Dr. Gutierrez discusses both the role of ultrasound imaging in the assessment of psoriatic arthritis (PsA) and his group’s development of a preliminary power Doppler ultrasound composite score for monitoring treatment of the disease (Rheumatology 2012 Feb. 29 [doi:10.1093/rheumatology/kes014]).

Question: What tools are currently being used for the global assessment of PsA?

Dr. Gutierrez: There are a variety of clinical instruments for measuring disease activity and treatment response in patients with PsA, including the Disease Activity Index for PsA (DAPSA), the PsA Response Criteria (PsARC), and the Disease Activity Score using 28 joint counts (DAS28), which was originally developed for patients with RA. The main weakness of the majority of these tools is that they are focused only on joint involvement and do not include measures of other key PsA targets, such as tendons, skin, and nails. Recently, the Composite Psoriatic Disease Activity Index (CPDAI) has been proposed, which includes multiple clinical domains – joints, tendons, and the spine – in its assessment. This tool provides more comprehensive information regarding disease activity, but it is limited by the absence of imaging findings, which offer a more objective measure of the global condition of the PsA patient.

Because a composite ultrasound score does not exist at present for PsA, we tested the possibility of using power Doppler ultrasound as a global measure of the inflammatory process to detect perfusion changes induced by tumor necrosis factor (TNF)-alpha antagonist, which have been shown in recent studies to be effective in improving functional outcomes and to arrest disease progression.

Question: How are the existing tools and measures insufficient? How would the power Doppler ultrasound composite score that your group has developed fill in the gaps?

Dr. Gutierrez: PsA is a chronic inflammatory disease. Its heterogeneity is such that the term "psoriatic disease" has been recently suggested to encompass the involvement at different tissue levels, including joints, tendons, enthesis, skin, and nails. Due to the high variability in the clinical course both within one patient and between patients, as well as the variability in the outcomes of PsA, no single measure can provide accurate information regarding disease activity and responsiveness in these patients.

The main disadvantage of the most commonly used clinical measures in the assessment of PsA is that they do not provide information on the real-time activity of the psoriatic disease. Rather, they provide information confined to the assessment of single domains separately. The alternative is individual evaluation of all targets. However, such an approach is associated with methodological and statistical problems, especially when these targets are employed as end points in clinical trials.

High-frequency ultrasound can detect not only structural abnormalities but also minimal blood flow changes at the superficial soft tissue level, making it a great tool for the global assessment of disease activity in psoriatic arthritis, in which persistently active disease plays a major role in causing anatomical damage and physical functional disability. Furthermore, the ability to measure global disease activity over time is important in assessing treatment efficacy in clinical trials and monitoring the patient’s course in daily care.

Additionally, pooling individual domains of disease activity into a composite ultrasound score offers a picture of disease activity along a continuous scale, and facilitates more consistency in the assessment and communication of disease activity and treatment response in research settings and clinical practice.

Question: Of the various imaging technologies, why is ultrasound the modality of choice for this application?

Dr. Gutierrez: Early detection and careful characterization of the inflammatory process in PsA play a key role in both diagnostic and therapeutic procedures. Ultrasound technology has the essential qualities to satisfy these fundamental necessities, including high- and variable-frequency probes and very sensitive power Doppler. These capabilities permit the study of structural changes with a resolution power of 0.1 mm and the sensitive detection of blood flow even in the small vessels of superficial tissues.

In addition to being sensitive enough to assess anatomical changes, disease activity, and therapeutic efficacy, ultrasound is safe, noninvasive, patient friendly, free of ionizing radiation, and less expensive than other imaging methods. It also allows multiple target assessment in real time without the need for external referral. Compared with conventional radiography, magnetic resonance imaging (MRI), or computed tomography (CT), power Doppler ultrasound can simultaneously reflect a change in inflammatory activity by accurately measuring blood flow changes and assess the progression of anatomical damage.

Question: What are the strengths and weaknesses of the preliminary power Doppler ultrasound composite score?

Dr. Gutierrez: Our preliminary composite score, called Five Targets Power Doppler for Psoriatic Disease (5TPD), includes the assessment of changes in joints, tendons with synovial sheath, entheses, skin, and nails. It represents a feasible, reliable, and comprehensive approach for multitarget monitoring of PsA.

The score is based on the simple arithmetic sum of the scores regarding the five clinical targets. Power Doppler for each target is graded from 0 to 3 on the basis of the semiquantitative scoring systems previously suggested. The maximum total score of 5TPDis 15. In our study, the instrument was found to possess both face and content validity, and it exhibited good responsiveness. By documenting these key measurement properties, we have shown that the 5TPD is a useful instrument for the assessment of disease activity and responsiveness in PsA patients and is, therefore, potentially applicable in standard clinical care, observational studies, and clinical trials.

The 5PTD is feasible and easy to perform in the hands of expert sonographers. The baseline assessment takes an average of 10.5 minutes. The follow-up complete examination, including calculating the score, averages no more than 7 minutes, which makes it quite practical in busy clinical settings.

The main limitation of the score currently is that it was tested in a small cohort of patients, which does not allow for an accurate evaluation in terms of the sensitivity and specificity needed to support our results more strongly. Also, we need to consider the ceiling effect. For example, high composite ultrasound scores denote the involvement of multiple target areas of psoriatic disease, and they can be shared by patients with relevant differences in terms of the extent of the inflammatory involvement at each specific target area. In other words, a severe inflammation of a single joint showing a power Doppler grade of 3 gives the maximum contribution to the final score; an equally severe inflammation in terms of power Doppler appearance, but polyarticular involvement, cannot provide more than 3 and thus would be easily underestimated. We are currently developing steps aimed at defining a linear cutoff value point for any single domain of 5TPD to resolve this aspect.

It is important to remember that this composite score was designed to monitor PsA disease activity in daily practice after a complete clinical examination, and not to replace other well-established and accepted ultrasound assessments.

Question: What is next for the 5TPD?

Dr. Gutierrez: Investigations are ongoing to assess the advantages and limitations of the formula in wider cohorts of patients. The composite score needs further development and concurrent and discriminate validation through randomized controlled trials and longitudinal observational studies. The tool is currently being evaluated prospectively as part of a larger multicenter study, as well as in a study comparing it with the CPDAI for the assessment of disease activity and responsiveness.

–Interview by Diana Mahoney

Dr. Gutierrez is scientific director of the Pan-American League of Associations for Rheumatology (PANLAR) Ultrasound Group. He reported having no financial conflicts of interest.

Musculoskeletal ultrasound is an efficient, noninvasive method for evaluating inflammatory and destructive changes in bone, cartilage, tendons, ligaments, and surrounding soft tissue of patients with psoriatic arthritis. The bedside technology allows the monitoring of all peripheral joints as frequently as needed in the management of early, active disease. Power Doppler ultrasound, in particular, can estimate increases in synovium, tendon sheaths, bursae, and enthesis. Thus it provides invaluable insight into disease status and progression, according to Dr. Marwin Gutierrez, assistant professor of rheumatology at Università Politecnica delle Marche in Ancona. Italy.

Despite its value, "[ultrasound] imaging is not firmly established in the assessment of treatment efficacy and monitoring of patient outcome in daily practice," said Dr. Gutierrez. And although joint, tendon, enthesis, skin, and nail involvement has been widely described by the different subset criteria as aspects to consider in psoriatic arthritis, "ultrasound research in the disease has relatively lagged behind that of rheumatoid arthritis [RA], with scarce validated imaging outcome measures," he said.

In this month’s column, Dr. Gutierrez discusses both the role of ultrasound imaging in the assessment of psoriatic arthritis (PsA) and his group’s development of a preliminary power Doppler ultrasound composite score for monitoring treatment of the disease (Rheumatology 2012 Feb. 29 [doi:10.1093/rheumatology/kes014]).

Question: What tools are currently being used for the global assessment of PsA?

Dr. Gutierrez: There are a variety of clinical instruments for measuring disease activity and treatment response in patients with PsA, including the Disease Activity Index for PsA (DAPSA), the PsA Response Criteria (PsARC), and the Disease Activity Score using 28 joint counts (DAS28), which was originally developed for patients with RA. The main weakness of the majority of these tools is that they are focused only on joint involvement and do not include measures of other key PsA targets, such as tendons, skin, and nails. Recently, the Composite Psoriatic Disease Activity Index (CPDAI) has been proposed, which includes multiple clinical domains – joints, tendons, and the spine – in its assessment. This tool provides more comprehensive information regarding disease activity, but it is limited by the absence of imaging findings, which offer a more objective measure of the global condition of the PsA patient.

Because a composite ultrasound score does not exist at present for PsA, we tested the possibility of using power Doppler ultrasound as a global measure of the inflammatory process to detect perfusion changes induced by tumor necrosis factor (TNF)-alpha antagonist, which have been shown in recent studies to be effective in improving functional outcomes and to arrest disease progression.

Question: How are the existing tools and measures insufficient? How would the power Doppler ultrasound composite score that your group has developed fill in the gaps?

Dr. Gutierrez: PsA is a chronic inflammatory disease. Its heterogeneity is such that the term "psoriatic disease" has been recently suggested to encompass the involvement at different tissue levels, including joints, tendons, enthesis, skin, and nails. Due to the high variability in the clinical course both within one patient and between patients, as well as the variability in the outcomes of PsA, no single measure can provide accurate information regarding disease activity and responsiveness in these patients.

The main disadvantage of the most commonly used clinical measures in the assessment of PsA is that they do not provide information on the real-time activity of the psoriatic disease. Rather, they provide information confined to the assessment of single domains separately. The alternative is individual evaluation of all targets. However, such an approach is associated with methodological and statistical problems, especially when these targets are employed as end points in clinical trials.

High-frequency ultrasound can detect not only structural abnormalities but also minimal blood flow changes at the superficial soft tissue level, making it a great tool for the global assessment of disease activity in psoriatic arthritis, in which persistently active disease plays a major role in causing anatomical damage and physical functional disability. Furthermore, the ability to measure global disease activity over time is important in assessing treatment efficacy in clinical trials and monitoring the patient’s course in daily care.

Additionally, pooling individual domains of disease activity into a composite ultrasound score offers a picture of disease activity along a continuous scale, and facilitates more consistency in the assessment and communication of disease activity and treatment response in research settings and clinical practice.

Question: Of the various imaging technologies, why is ultrasound the modality of choice for this application?

Dr. Gutierrez: Early detection and careful characterization of the inflammatory process in PsA play a key role in both diagnostic and therapeutic procedures. Ultrasound technology has the essential qualities to satisfy these fundamental necessities, including high- and variable-frequency probes and very sensitive power Doppler. These capabilities permit the study of structural changes with a resolution power of 0.1 mm and the sensitive detection of blood flow even in the small vessels of superficial tissues.

In addition to being sensitive enough to assess anatomical changes, disease activity, and therapeutic efficacy, ultrasound is safe, noninvasive, patient friendly, free of ionizing radiation, and less expensive than other imaging methods. It also allows multiple target assessment in real time without the need for external referral. Compared with conventional radiography, magnetic resonance imaging (MRI), or computed tomography (CT), power Doppler ultrasound can simultaneously reflect a change in inflammatory activity by accurately measuring blood flow changes and assess the progression of anatomical damage.

Question: What are the strengths and weaknesses of the preliminary power Doppler ultrasound composite score?

Dr. Gutierrez: Our preliminary composite score, called Five Targets Power Doppler for Psoriatic Disease (5TPD), includes the assessment of changes in joints, tendons with synovial sheath, entheses, skin, and nails. It represents a feasible, reliable, and comprehensive approach for multitarget monitoring of PsA.

The score is based on the simple arithmetic sum of the scores regarding the five clinical targets. Power Doppler for each target is graded from 0 to 3 on the basis of the semiquantitative scoring systems previously suggested. The maximum total score of 5TPDis 15. In our study, the instrument was found to possess both face and content validity, and it exhibited good responsiveness. By documenting these key measurement properties, we have shown that the 5TPD is a useful instrument for the assessment of disease activity and responsiveness in PsA patients and is, therefore, potentially applicable in standard clinical care, observational studies, and clinical trials.

The 5PTD is feasible and easy to perform in the hands of expert sonographers. The baseline assessment takes an average of 10.5 minutes. The follow-up complete examination, including calculating the score, averages no more than 7 minutes, which makes it quite practical in busy clinical settings.

The main limitation of the score currently is that it was tested in a small cohort of patients, which does not allow for an accurate evaluation in terms of the sensitivity and specificity needed to support our results more strongly. Also, we need to consider the ceiling effect. For example, high composite ultrasound scores denote the involvement of multiple target areas of psoriatic disease, and they can be shared by patients with relevant differences in terms of the extent of the inflammatory involvement at each specific target area. In other words, a severe inflammation of a single joint showing a power Doppler grade of 3 gives the maximum contribution to the final score; an equally severe inflammation in terms of power Doppler appearance, but polyarticular involvement, cannot provide more than 3 and thus would be easily underestimated. We are currently developing steps aimed at defining a linear cutoff value point for any single domain of 5TPD to resolve this aspect.

It is important to remember that this composite score was designed to monitor PsA disease activity in daily practice after a complete clinical examination, and not to replace other well-established and accepted ultrasound assessments.

Question: What is next for the 5TPD?

Dr. Gutierrez: Investigations are ongoing to assess the advantages and limitations of the formula in wider cohorts of patients. The composite score needs further development and concurrent and discriminate validation through randomized controlled trials and longitudinal observational studies. The tool is currently being evaluated prospectively as part of a larger multicenter study, as well as in a study comparing it with the CPDAI for the assessment of disease activity and responsiveness.

–Interview by Diana Mahoney

Dr. Gutierrez is scientific director of the Pan-American League of Associations for Rheumatology (PANLAR) Ultrasound Group. He reported having no financial conflicts of interest.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at pdnews@elsevier.com.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at pdnews@elsevier.com.

Warmer temperatures in the United States are leading to the earlier presence of mosquitoes and the potential for mosquito-borne illnesses.

There are a number of arboviral diseases that occur in the United States, including St. Louis and La Cross encephalitis. Since its emergence in 1999, clinicians in the United States have been familiar with West Nile virus. Dengue is one you may not know as much about, and it has the potential to reestablish itself in the United States. Here’s a quick review.

An emerging infection, dengue is transmitted by the mosquitoes Aedes aegypti and A. albopictus, which are found worldwide. The dengue virus complex consists of four related, but distinct, serotypes. Infection with one confers lifelong immunity, but there is no cross-protection against the other serotypes. Dengue fever (DF) is endemic in at least 100 countries in Asia, the Pacific, the Americas, Africa, and the Caribbean. It often peaks during seasons when rainfall is optimal for mosquito breeding. The Aedes mosquito is common in the southern United States, and dengue is endemic in northern Mexico. Most cases in the United States are seen in returning travelers or immigrants (MMWR 2005;54;556-8), including children (Am. J. Trop. Med. Hyg. 2012;86:474-6).

Since 1980 there have been seven outbreaks along the Texas-Mexico border. However, dengue can be acquired locally. In 2010, 28 cases were reported from Key West, Fla. They were the first cases of locally acquired dengue outside the Texas-Mexico border since 1995. The initial case was diagnosed by an astute physician in a patient from New York who had visited Key West (MMWR 2010;59:577-81).

Why is this virus reemerging in the United States? One thought is that the mosquito vector has optimal breeding conditions. It prefers to breed close to or inside a home, and it can lay eggs in natural or man-made water containers. It also is a daytime feeder with a preference for humans. Often, the mosquito has multiple feeds before a breeding cycle, thus exposing several persons in the same household.

Dengue should be considered in the differential diagnosis of all febrile patients who reside in the tropics or subtropics, including areas with subtropical climates in the United States, or in febrile patients who have a history of travel to such places in the 2 weeks before symptom onset. It is now the leading cause of a febrile illness in U.S. travelers returning from the Caribbean, South America, and Asia (N. Eng. J. Med. 2006;354:119-30). Because of the increasing number of cases in returning travelers, many of whom may still be viremic and capable of introducing the virus into the community, combined with the presence of an efficient mosquito vector, dengue became a nationally notifiable disease in 2009.

Symptoms typically begin 4-7 days after the mosquito bite and last about 3-10 days. Individuals, especially children, infected with dengue for the first time may be asymptomatic or have a nonspecific febrile illness, but subsequent infections are usually more severe. Classic DF is primarily a disease of older children and adults.

The World Health Organization defines DF as an acute febrile illness with two or more of the following: headache, retro-orbital pain, muscle aches, joint pain, rash, hemorrhagic manifestation, or leukopenia. The rash is either macular or maculopapular and generalized, is often confluent with small patches of normal skin, and may become scaly and pruritic. It usually appears as the fever subsides and lasts 2-4 days. Other signs and symptoms include flushed skin (usually during the first 24-48 hours), nausea, and vomiting. DF is usually a self-limited illness and is rarely fatal. Approximately 1% of patients with DF develop dengue hemorrhagic fever about 3-8 days after the onset of fever. There is evidence of vascular leakage, hemoconcentration, and thrombocytopenia.

Courtesy Jim Gathany/CDC

The primary serologic test for dengue virus (DENV) in patients with acute illness is IgM anti-DENV, which becomes positive more than 5 days after symptom onset. This, in combination with a compatible travel history and symptom profile, suggests a probable recent DENV infection. There are several commercially available diagnostic tests for dengue, although none have been approved by the Food and Drug Administration. Testing is available at some state laboratories, and through the Centers for Disease Control and Prevention (see "Requesting Dengue Laboratory Testing and Reporting" at www.cdc.gov/Dengue/clinicalLab/index.html). For additional information, contact the CDC Dengue Branch (787-706-2399) or visit http://www.cdc.gov/dengue/.

There is no specific treatment for DENV infections. Management involves bed rest and fluid maintenance during the fever, which can be controlled with acetaminophen. Headache, eye pain, joint pain, and muscle ache may require narcotics, but aspirin and nonsteroidal anti-inflammatory agents should be avoided. Patients should be instructed that, as the fever subsides, they should go to the hospital if they develop abrupt change to hypothermia, severe abdominal pain, persistent vomiting, bleeding, difficulties breathing, or altered mental status such as irritability, confusion, and lethargy. These may be signs of dengue hemorrhagic fever, which can prove fatal.

Prevention is the best bet. Travelers should be advised to use insecticides to get rid of mosquitoes in these areas and to select accommodations with well-screened windows or air conditioning when possible. Additionally, travelers should take measures to avoid being bitten by mosquitoes during the daytime. Children at least 3 months of age can use a repellant containing not more than 30% DEET. Younger infants should have permethrin-treated nets placed over carriers. Everyone can benefit from permethrin-treated clothing, as well as from eliminating or avoiding standing water.

Currently, there is no licensed vaccine available. However, Sanofi Pasteur has a tetravalent vaccine in phase III clinical trials.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at pdnews@elsevier.com.

MIAMI BEACH – Knowing if immunomodulators should be stopped in the perioperative period and when would be helpful for hospitalists, surgeons, other clinicians and, ultimately, for patients.

It is important to balance the concerns of patient optimization for surgery vs. the risk of triggering a recurrent inflammatory cascade or organ rejection during cessation, Dr. Christopher Whinney said at a meeting on perioperative medicine sponsored by the University of Miami.

Although there is a dearth of randomized controlled trials to address immunomodulator cessation around the time of surgery, Dr. Whinney reviewed what evidence is available (mostly observational and/or retrospective studies). He provided specific advice regarding tumor necrosis factor (TNF) alpha inhibitors, corticosteroids, calcineurin inhibitors, antiproliferative agents such as mycophenolate mofetil, and mammalian target of rapamycin inhibitors (mTOR).

There is some controversy regarding continuation of TNF-alpha inhibitors during the perioperative period, for example, said Dr. Whinney, chairman of the department of hospital medicine at the Cleveland Clinic. "Some studies suggest an increased risk for [surgical site] infection and others do not. The literature is heterogenous in this area."

Continuation of TNF-alpha agents in patients with rheumatoid arthritis, for example, was not associated with increased risk of surgical site infections in a retrospective study of 1,219 surgical procedures performed in 768 patients (J. Rheum. 2007;34:689-95). In contrast, other researchers conducted a systematic literature review and determined there is evidence of an increased risk of serious infection with TNF-alpha inhibitor use, in general, among patients with rheumatoid arthritis (JAMA 2006;295:2275-85).

"It’s a judgment call," Dr. Whinney said. "Although the weight of evidence suggests the safety of continuation ... my practice would be to withhold these 2 weeks preoperatively, of course in discussion with the rheumatologist or person prescribing these agents."

Corticosteroid supplementation in the perioperative setting is another question with no definitive answer in the literature. Whether or not to provide high "stress dose" steroids on the morning of surgery to minimize the potential for an adrenal crisis in patients with adrenal insufficiency is a question. The stress of surgery can activate the brain’s hypothalamic-pituitary-adrenal (HPA) axis and trigger a rare but serious adrenal crisis. The thinking is that high-dose steroids will suppress the HPA axis activation and prevent these rare crises.

"Current supplementation is probably excessive. We probably give way too [many] stress dose steroids ... and are probably treating ourselves more than we are treating our patients," Dr. Whinney said.

A Cochrane database review supports this position (Cochrane Database Syst. Rev. 2009;4:CD005367).Dr. Whinney said this review revealed that for patients on basal steroid doses, "it was not possible to refute or support perioperative steroid supplementation."

"For most patients who are on steroids for a reason other than existing HPA axis disease, for most surgeries, their daily steroid regimen is acceptable."

Other researchers recommended an amount of steroid supplementation to administer according to surgery type: superficial, minor, moderate, or major (Semin. Arthritis Rheum. 2007;36:278-86).

Aminosalicylates are another type of immunomodulator relevant in the perioperative period. These anti-inflammatory agents are taken by patients with ulcerative colitis or Crohn’s disease. There are little data on perioperative use of these agents, which include sulfasalazine or 5-aminosalicylate, Dr. Whinney said.

Some researchers suggest holding aminosalicylates on the day of surgery for patients with inflammatory bowel disease who are renally cleared, if they have a diminished glomerular filtration rate (for example, patients older than 65 years, those with ASA physical status score of 4 or 5, and/or patients with a revised cardiac risk index score greater than 2) (Mayo Clin. Proc. 2011;86:748-57). This protocol permits reinitiating aminosalicylates on postoperative day 3.

Patients also might present for surgery taking one of the potent calcineurin inhibitors such as cyclosporine or tacrolimus. Although there is no evidence of increased postoperative complications when these agents are continued perioperatively, continue to watch patients for infection and continue to monitor drug levels, Dr. Whinney said. He also recommended switching patients to an intravenous form if they are NPO (nothing by mouth) for an extended time or are placed on mechanical ventilation for more than 24 hours. It is important to consult a transplant surgeon regarding these agents.

Azathioprine and 6-mercaptopurine are antiproliferative agents often administered for their steroid sparing effects. There have been no consistent effects on surgical outcomes or mortality reported, Dr. Whinney said. However, it is probably reasonable to hold these agents on the day of surgery and resume on the third postoperative day, mostly to avoid any adverse effect on anesthesia. Have a conversation with the prescribing physician, he added, before you stop these agents perioperatively.

Mycophenolate mofetil is another antiproliferative agent. Hepatic and renal testing is appropriate if someone is already on these agents. Although there are little to no data to guide perioperative use, "it can be continued in the perioperative period in absence of infection or liver or renal disease," according to Dr. Whinney.

Sirolimus and everolimus are potent antiproliferative agents in the mTOR inhibitor class. An increased risk for wound complications or wound seromas is a relevant perioperative issue. Obesity and concomitant use of steroids add to this risk. A systematic wound care program can reduce the rate of wound healing complications back to baseline, Dr. Whinney said.

Dr. Whinney recommended stopping sirolimus or everolimus 2-4 weeks prior to major or abdominal surgery to allow clearance of this long half-life agent from the body. Replace the agent with an appropriate calcineurin inhibitor. "Again, if you are unfamiliar with these agents, use them in conjunction with a transplant specialist."

Dr. Whinney is a speaker and consultant for Sanofi Aventis.

MIAMI BEACH – Knowing if immunomodulators should be stopped in the perioperative period and when would be helpful for hospitalists, surgeons, other clinicians and, ultimately, for patients.

It is important to balance the concerns of patient optimization for surgery vs. the risk of triggering a recurrent inflammatory cascade or organ rejection during cessation, Dr. Christopher Whinney said at a meeting on perioperative medicine sponsored by the University of Miami.

Although there is a dearth of randomized controlled trials to address immunomodulator cessation around the time of surgery, Dr. Whinney reviewed what evidence is available (mostly observational and/or retrospective studies). He provided specific advice regarding tumor necrosis factor (TNF) alpha inhibitors, corticosteroids, calcineurin inhibitors, antiproliferative agents such as mycophenolate mofetil, and mammalian target of rapamycin inhibitors (mTOR).

There is some controversy regarding continuation of TNF-alpha inhibitors during the perioperative period, for example, said Dr. Whinney, chairman of the department of hospital medicine at the Cleveland Clinic. "Some studies suggest an increased risk for [surgical site] infection and others do not. The literature is heterogenous in this area."

Continuation of TNF-alpha agents in patients with rheumatoid arthritis, for example, was not associated with increased risk of surgical site infections in a retrospective study of 1,219 surgical procedures performed in 768 patients (J. Rheum. 2007;34:689-95). In contrast, other researchers conducted a systematic literature review and determined there is evidence of an increased risk of serious infection with TNF-alpha inhibitor use, in general, among patients with rheumatoid arthritis (JAMA 2006;295:2275-85).

"It’s a judgment call," Dr. Whinney said. "Although the weight of evidence suggests the safety of continuation ... my practice would be to withhold these 2 weeks preoperatively, of course in discussion with the rheumatologist or person prescribing these agents."

Corticosteroid supplementation in the perioperative setting is another question with no definitive answer in the literature. Whether or not to provide high "stress dose" steroids on the morning of surgery to minimize the potential for an adrenal crisis in patients with adrenal insufficiency is a question. The stress of surgery can activate the brain’s hypothalamic-pituitary-adrenal (HPA) axis and trigger a rare but serious adrenal crisis. The thinking is that high-dose steroids will suppress the HPA axis activation and prevent these rare crises.

"Current supplementation is probably excessive. We probably give way too [many] stress dose steroids ... and are probably treating ourselves more than we are treating our patients," Dr. Whinney said.

A Cochrane database review supports this position (Cochrane Database Syst. Rev. 2009;4:CD005367).Dr. Whinney said this review revealed that for patients on basal steroid doses, "it was not possible to refute or support perioperative steroid supplementation."

"For most patients who are on steroids for a reason other than existing HPA axis disease, for most surgeries, their daily steroid regimen is acceptable."

Other researchers recommended an amount of steroid supplementation to administer according to surgery type: superficial, minor, moderate, or major (Semin. Arthritis Rheum. 2007;36:278-86).

Aminosalicylates are another type of immunomodulator relevant in the perioperative period. These anti-inflammatory agents are taken by patients with ulcerative colitis or Crohn’s disease. There are little data on perioperative use of these agents, which include sulfasalazine or 5-aminosalicylate, Dr. Whinney said.

Some researchers suggest holding aminosalicylates on the day of surgery for patients with inflammatory bowel disease who are renally cleared, if they have a diminished glomerular filtration rate (for example, patients older than 65 years, those with ASA physical status score of 4 or 5, and/or patients with a revised cardiac risk index score greater than 2) (Mayo Clin. Proc. 2011;86:748-57). This protocol permits reinitiating aminosalicylates on postoperative day 3.

Patients also might present for surgery taking one of the potent calcineurin inhibitors such as cyclosporine or tacrolimus. Although there is no evidence of increased postoperative complications when these agents are continued perioperatively, continue to watch patients for infection and continue to monitor drug levels, Dr. Whinney said. He also recommended switching patients to an intravenous form if they are NPO (nothing by mouth) for an extended time or are placed on mechanical ventilation for more than 24 hours. It is important to consult a transplant surgeon regarding these agents.

Azathioprine and 6-mercaptopurine are antiproliferative agents often administered for their steroid sparing effects. There have been no consistent effects on surgical outcomes or mortality reported, Dr. Whinney said. However, it is probably reasonable to hold these agents on the day of surgery and resume on the third postoperative day, mostly to avoid any adverse effect on anesthesia. Have a conversation with the prescribing physician, he added, before you stop these agents perioperatively.

Mycophenolate mofetil is another antiproliferative agent. Hepatic and renal testing is appropriate if someone is already on these agents. Although there are little to no data to guide perioperative use, "it can be continued in the perioperative period in absence of infection or liver or renal disease," according to Dr. Whinney.

Sirolimus and everolimus are potent antiproliferative agents in the mTOR inhibitor class. An increased risk for wound complications or wound seromas is a relevant perioperative issue. Obesity and concomitant use of steroids add to this risk. A systematic wound care program can reduce the rate of wound healing complications back to baseline, Dr. Whinney said.

Dr. Whinney recommended stopping sirolimus or everolimus 2-4 weeks prior to major or abdominal surgery to allow clearance of this long half-life agent from the body. Replace the agent with an appropriate calcineurin inhibitor. "Again, if you are unfamiliar with these agents, use them in conjunction with a transplant specialist."

Dr. Whinney is a speaker and consultant for Sanofi Aventis.

MIAMI BEACH – Knowing if immunomodulators should be stopped in the perioperative period and when would be helpful for hospitalists, surgeons, other clinicians and, ultimately, for patients.

It is important to balance the concerns of patient optimization for surgery vs. the risk of triggering a recurrent inflammatory cascade or organ rejection during cessation, Dr. Christopher Whinney said at a meeting on perioperative medicine sponsored by the University of Miami.

Although there is a dearth of randomized controlled trials to address immunomodulator cessation around the time of surgery, Dr. Whinney reviewed what evidence is available (mostly observational and/or retrospective studies). He provided specific advice regarding tumor necrosis factor (TNF) alpha inhibitors, corticosteroids, calcineurin inhibitors, antiproliferative agents such as mycophenolate mofetil, and mammalian target of rapamycin inhibitors (mTOR).

There is some controversy regarding continuation of TNF-alpha inhibitors during the perioperative period, for example, said Dr. Whinney, chairman of the department of hospital medicine at the Cleveland Clinic. "Some studies suggest an increased risk for [surgical site] infection and others do not. The literature is heterogenous in this area."

Continuation of TNF-alpha agents in patients with rheumatoid arthritis, for example, was not associated with increased risk of surgical site infections in a retrospective study of 1,219 surgical procedures performed in 768 patients (J. Rheum. 2007;34:689-95). In contrast, other researchers conducted a systematic literature review and determined there is evidence of an increased risk of serious infection with TNF-alpha inhibitor use, in general, among patients with rheumatoid arthritis (JAMA 2006;295:2275-85).

"It’s a judgment call," Dr. Whinney said. "Although the weight of evidence suggests the safety of continuation ... my practice would be to withhold these 2 weeks preoperatively, of course in discussion with the rheumatologist or person prescribing these agents."

Corticosteroid supplementation in the perioperative setting is another question with no definitive answer in the literature. Whether or not to provide high "stress dose" steroids on the morning of surgery to minimize the potential for an adrenal crisis in patients with adrenal insufficiency is a question. The stress of surgery can activate the brain’s hypothalamic-pituitary-adrenal (HPA) axis and trigger a rare but serious adrenal crisis. The thinking is that high-dose steroids will suppress the HPA axis activation and prevent these rare crises.

"Current supplementation is probably excessive. We probably give way too [many] stress dose steroids ... and are probably treating ourselves more than we are treating our patients," Dr. Whinney said.

A Cochrane database review supports this position (Cochrane Database Syst. Rev. 2009;4:CD005367).Dr. Whinney said this review revealed that for patients on basal steroid doses, "it was not possible to refute or support perioperative steroid supplementation."

"For most patients who are on steroids for a reason other than existing HPA axis disease, for most surgeries, their daily steroid regimen is acceptable."

Other researchers recommended an amount of steroid supplementation to administer according to surgery type: superficial, minor, moderate, or major (Semin. Arthritis Rheum. 2007;36:278-86).

Aminosalicylates are another type of immunomodulator relevant in the perioperative period. These anti-inflammatory agents are taken by patients with ulcerative colitis or Crohn’s disease. There are little data on perioperative use of these agents, which include sulfasalazine or 5-aminosalicylate, Dr. Whinney said.

Some researchers suggest holding aminosalicylates on the day of surgery for patients with inflammatory bowel disease who are renally cleared, if they have a diminished glomerular filtration rate (for example, patients older than 65 years, those with ASA physical status score of 4 or 5, and/or patients with a revised cardiac risk index score greater than 2) (Mayo Clin. Proc. 2011;86:748-57). This protocol permits reinitiating aminosalicylates on postoperative day 3.

Patients also might present for surgery taking one of the potent calcineurin inhibitors such as cyclosporine or tacrolimus. Although there is no evidence of increased postoperative complications when these agents are continued perioperatively, continue to watch patients for infection and continue to monitor drug levels, Dr. Whinney said. He also recommended switching patients to an intravenous form if they are NPO (nothing by mouth) for an extended time or are placed on mechanical ventilation for more than 24 hours. It is important to consult a transplant surgeon regarding these agents.

Azathioprine and 6-mercaptopurine are antiproliferative agents often administered for their steroid sparing effects. There have been no consistent effects on surgical outcomes or mortality reported, Dr. Whinney said. However, it is probably reasonable to hold these agents on the day of surgery and resume on the third postoperative day, mostly to avoid any adverse effect on anesthesia. Have a conversation with the prescribing physician, he added, before you stop these agents perioperatively.

Mycophenolate mofetil is another antiproliferative agent. Hepatic and renal testing is appropriate if someone is already on these agents. Although there are little to no data to guide perioperative use, "it can be continued in the perioperative period in absence of infection or liver or renal disease," according to Dr. Whinney.

Sirolimus and everolimus are potent antiproliferative agents in the mTOR inhibitor class. An increased risk for wound complications or wound seromas is a relevant perioperative issue. Obesity and concomitant use of steroids add to this risk. A systematic wound care program can reduce the rate of wound healing complications back to baseline, Dr. Whinney said.

Dr. Whinney recommended stopping sirolimus or everolimus 2-4 weeks prior to major or abdominal surgery to allow clearance of this long half-life agent from the body. Replace the agent with an appropriate calcineurin inhibitor. "Again, if you are unfamiliar with these agents, use them in conjunction with a transplant specialist."

Dr. Whinney is a speaker and consultant for Sanofi Aventis.

PALM SPRINGS, CALIF. (EGMN) – A parasagittal approach – but not a midline approach – to interlaminar lumbar epidural steroid injections for unilateral lumbosacral radiculopathic pain significantly improved quality of life and functionality in a prospective, randomized, single-blind study of 44 adults.

The steroid injections significantly improved pain in both groups, with Numeric Rating Scale scores during movement decreasing from a preinjection average of 8 in the parasagittal group and 7 in the midline group, to 3 and 4, respectively, on days 1, 7, and 28 after injection. Pain scores at rest decreased from 5 in both groups before injection to 3 in the parasagittal group and 4 in the midline group on follow-up days 1, 7, and 28, Dr. Kenneth D. Candido and his associates reported in a prize-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

"The analgesic benefit is profound over the first 30 days; it’s about 50%," he said. There have been few previous reports, however, assessing quality of life and functionality after interlaminar lumbar epidural steroid injections, said Dr. Candido of Advocate Illinois Masonic Medical Center, Chicago.

All patients completed the Oswestry Low Back Pain Questionnaire 20 minutes before injection and at each of the follow-ups. The questionnaire is designed to assess how back pain affects patients’ ability to manage in everyday life, with sections focused on impairments (such as pain) and abilities, including personal care, lifting, walking, sitting, standing, sleeping, social life, sex life, and traveling.

Oswestry scores averaged 21 in the parasagittal group and 20 in the midline group before injection, a difference that was not significant. Scores improved in both groups after injection, but only the parasagittal group showed statistically significant improvements compared with baseline.

Oswestry scores decreased in the parasagittal group from 21 at baseline to approximately 12 on follow-up day 1, and to approximately 10 on days 7 and 28. Oswestry scores in the midline group decreased from 20 at baseline to approximately 15 on follow-up day 1, to 13 on day 7, and to 12 on day 28.

The results suggest that the parasagittal approach was more effective than the midline approach in patients with unilateral lumbosacral radiculopathic pain, Dr. Candido said.

Both approaches to lumbar epidural steroid injections are accepted treatments in the conservative care of low back pain with radiculopathy secondary to lumbar disk disease, but there are few previous data on functional improvements after lumbar epidural steroid injections. "I regularly practice both of these in my practice," he said.

Patients were randomized to the parasagittal or midline interlaminar approach. All received 120 mg (2 mL) of methylprednisolone acetate with 1 mL of normal saline solution and 1 mL of lidocaine 1%.

The ongoing study has randomized 55 more patients, and the investigators are gathering data from 6 months of follow-up.

Patient characteristics were similar between groups. The average age was 49 years in the parasagittal group and 50 in the midline group. Approximately half in each group were male. Low back pain symptoms had been present for an average of 18 months in the parasagittal group and 24 months in the midline group.

The study excluded patients with discogenic pain without radiculopathic pain; a history of previous spinal surgery; a lumbar epidural steroid injection in the past year; allergy to methylprednisolone, lidocaine, or iodine-based contrast; concurrent use of systemic steroid medications; or habituation to opioids.

Dr. Candido reported having no financial disclosures.

PALM SPRINGS, CALIF. (EGMN) – A parasagittal approach – but not a midline approach – to interlaminar lumbar epidural steroid injections for unilateral lumbosacral radiculopathic pain significantly improved quality of life and functionality in a prospective, randomized, single-blind study of 44 adults.

The steroid injections significantly improved pain in both groups, with Numeric Rating Scale scores during movement decreasing from a preinjection average of 8 in the parasagittal group and 7 in the midline group, to 3 and 4, respectively, on days 1, 7, and 28 after injection. Pain scores at rest decreased from 5 in both groups before injection to 3 in the parasagittal group and 4 in the midline group on follow-up days 1, 7, and 28, Dr. Kenneth D. Candido and his associates reported in a prize-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

"The analgesic benefit is profound over the first 30 days; it’s about 50%," he said. There have been few previous reports, however, assessing quality of life and functionality after interlaminar lumbar epidural steroid injections, said Dr. Candido of Advocate Illinois Masonic Medical Center, Chicago.

All patients completed the Oswestry Low Back Pain Questionnaire 20 minutes before injection and at each of the follow-ups. The questionnaire is designed to assess how back pain affects patients’ ability to manage in everyday life, with sections focused on impairments (such as pain) and abilities, including personal care, lifting, walking, sitting, standing, sleeping, social life, sex life, and traveling.

Oswestry scores averaged 21 in the parasagittal group and 20 in the midline group before injection, a difference that was not significant. Scores improved in both groups after injection, but only the parasagittal group showed statistically significant improvements compared with baseline.

Oswestry scores decreased in the parasagittal group from 21 at baseline to approximately 12 on follow-up day 1, and to approximately 10 on days 7 and 28. Oswestry scores in the midline group decreased from 20 at baseline to approximately 15 on follow-up day 1, to 13 on day 7, and to 12 on day 28.

The results suggest that the parasagittal approach was more effective than the midline approach in patients with unilateral lumbosacral radiculopathic pain, Dr. Candido said.

Both approaches to lumbar epidural steroid injections are accepted treatments in the conservative care of low back pain with radiculopathy secondary to lumbar disk disease, but there are few previous data on functional improvements after lumbar epidural steroid injections. "I regularly practice both of these in my practice," he said.

Patients were randomized to the parasagittal or midline interlaminar approach. All received 120 mg (2 mL) of methylprednisolone acetate with 1 mL of normal saline solution and 1 mL of lidocaine 1%.

The ongoing study has randomized 55 more patients, and the investigators are gathering data from 6 months of follow-up.

Patient characteristics were similar between groups. The average age was 49 years in the parasagittal group and 50 in the midline group. Approximately half in each group were male. Low back pain symptoms had been present for an average of 18 months in the parasagittal group and 24 months in the midline group.

The study excluded patients with discogenic pain without radiculopathic pain; a history of previous spinal surgery; a lumbar epidural steroid injection in the past year; allergy to methylprednisolone, lidocaine, or iodine-based contrast; concurrent use of systemic steroid medications; or habituation to opioids.

Dr. Candido reported having no financial disclosures.

PALM SPRINGS, CALIF. (EGMN) – A parasagittal approach – but not a midline approach – to interlaminar lumbar epidural steroid injections for unilateral lumbosacral radiculopathic pain significantly improved quality of life and functionality in a prospective, randomized, single-blind study of 44 adults.

The steroid injections significantly improved pain in both groups, with Numeric Rating Scale scores during movement decreasing from a preinjection average of 8 in the parasagittal group and 7 in the midline group, to 3 and 4, respectively, on days 1, 7, and 28 after injection. Pain scores at rest decreased from 5 in both groups before injection to 3 in the parasagittal group and 4 in the midline group on follow-up days 1, 7, and 28, Dr. Kenneth D. Candido and his associates reported in a prize-winning poster and plenary presentation at the annual meeting of the American Academy of Pain Medicine.

"The analgesic benefit is profound over the first 30 days; it’s about 50%," he said. There have been few previous reports, however, assessing quality of life and functionality after interlaminar lumbar epidural steroid injections, said Dr. Candido of Advocate Illinois Masonic Medical Center, Chicago.

All patients completed the Oswestry Low Back Pain Questionnaire 20 minutes before injection and at each of the follow-ups. The questionnaire is designed to assess how back pain affects patients’ ability to manage in everyday life, with sections focused on impairments (such as pain) and abilities, including personal care, lifting, walking, sitting, standing, sleeping, social life, sex life, and traveling.

Oswestry scores averaged 21 in the parasagittal group and 20 in the midline group before injection, a difference that was not significant. Scores improved in both groups after injection, but only the parasagittal group showed statistically significant improvements compared with baseline.

Oswestry scores decreased in the parasagittal group from 21 at baseline to approximately 12 on follow-up day 1, and to approximately 10 on days 7 and 28. Oswestry scores in the midline group decreased from 20 at baseline to approximately 15 on follow-up day 1, to 13 on day 7, and to 12 on day 28.

The results suggest that the parasagittal approach was more effective than the midline approach in patients with unilateral lumbosacral radiculopathic pain, Dr. Candido said.

Both approaches to lumbar epidural steroid injections are accepted treatments in the conservative care of low back pain with radiculopathy secondary to lumbar disk disease, but there are few previous data on functional improvements after lumbar epidural steroid injections. "I regularly practice both of these in my practice," he said.

Patients were randomized to the parasagittal or midline interlaminar approach. All received 120 mg (2 mL) of methylprednisolone acetate with 1 mL of normal saline solution and 1 mL of lidocaine 1%.

The ongoing study has randomized 55 more patients, and the investigators are gathering data from 6 months of follow-up.

Patient characteristics were similar between groups. The average age was 49 years in the parasagittal group and 50 in the midline group. Approximately half in each group were male. Low back pain symptoms had been present for an average of 18 months in the parasagittal group and 24 months in the midline group.

The study excluded patients with discogenic pain without radiculopathic pain; a history of previous spinal surgery; a lumbar epidural steroid injection in the past year; allergy to methylprednisolone, lidocaine, or iodine-based contrast; concurrent use of systemic steroid medications; or habituation to opioids.

Dr. Candido reported having no financial disclosures.