Bruce Jancin

NEW ORLEANS – The traditional Chinese medical therapy known as quigong exercise resulted in significant reduction in fatigue scores in patients with chronic fatigue syndrome in a randomized controlled trial.

Qigong also led to significant improvement in validated measures of mental and physical health and spiritual well-being, Jessie S.M. Chan reported at the annual meeting of the Society of Behavioral Medicine.

Photo ©Anna Furman/iStockphoto.com

A dose-response effect was evident. Practicing qigong for at least 30 minutes on at least 3 days per week produced better outcomes, according to Ms. Chan, a doctoral candidate at the University of Hong Kong.

Qigong, translated as "life energy cultivation," is an ancient Taoist art of self-healing. It’s an increasingly popular form of complementary and alternative medicine in the United States. It combines regulation of the body, mind, and breath through a program of gentle exercises and meditation.

From a traditional Chinese medicine perspective, Ms. Chan explained, chronic fatigue syndrome is caused by blood stasis due to a deficiency of Qi, or vital energy. The key treatment strategy entails restoring the balance between yin and yang and stimulation of the blood to get the Qi circulating.

From the perspective of the busy Western primary care physician, of course, chronic fatigue syndrome is an often frustrating condition for which up until now only two interventions have been shown beneficial: cognitive behavioral therapy and graded exercise training.

The randomized trial included 154 patients aged 18-55 years with unexplained chronic fatigue of at least 6 months duration plus multiple other findings consistent with the Centers for Disease Control and Prevention definition of chronic fatigue syndrome. While participants met criteria for the syndrome, most of them did not carry a formal physician diagnosis, and thus would most accurately be said to have chronic fatigue syndrome–like illness, she noted.

Subjects were randomized to two group qigong sessions per week for 5 weeks, with each session lasting 2 hours, along with a recommended 15-30 minutes per day of practice at home, or to a wait-list control group. This was wu xing ping heng gong–style qigong. The movements, consisting of 10 forms, were typically performed in the morning, whereas the meditation was done at night before going to sleep. The focus of the meditation was simply on diaphragmatic breathing.

The primary study end point was change in the 14-item Chalder Fatigue Scale from baseline through 5 weeks of qigong. Subjects in the qigong arm demonstrated a 39% reduction in their total score, while scores in the control arm didn’t change significantly (39.7 vs. 24.4 in the quigong arm compared with 39.8 vs. 34.1 in the control arm). The qigong group also displayed significant improvements in the Short Form-12 physical and mental component scores and the Body-Mind-Spirit Integrative Well-Being score (see chart).

Many patients found the full qigong regimen too arduous or time consuming. Those who practiced qigong at least three times per week and spent an average of 30 minutes or more per session showed nearly twice as great an improvement in Chalder scores as those who did less.

The trial was sponsored by the University of Hong Kong Center on Behavioral Health. Ms. Chan reported having no financial conflicts.

NEW ORLEANS – The traditional Chinese medical therapy known as quigong exercise resulted in significant reduction in fatigue scores in patients with chronic fatigue syndrome in a randomized controlled trial.

Qigong also led to significant improvement in validated measures of mental and physical health and spiritual well-being, Jessie S.M. Chan reported at the annual meeting of the Society of Behavioral Medicine.

Photo ©Anna Furman/iStockphoto.com

A dose-response effect was evident. Practicing qigong for at least 30 minutes on at least 3 days per week produced better outcomes, according to Ms. Chan, a doctoral candidate at the University of Hong Kong.

Qigong, translated as "life energy cultivation," is an ancient Taoist art of self-healing. It’s an increasingly popular form of complementary and alternative medicine in the United States. It combines regulation of the body, mind, and breath through a program of gentle exercises and meditation.

From a traditional Chinese medicine perspective, Ms. Chan explained, chronic fatigue syndrome is caused by blood stasis due to a deficiency of Qi, or vital energy. The key treatment strategy entails restoring the balance between yin and yang and stimulation of the blood to get the Qi circulating.

From the perspective of the busy Western primary care physician, of course, chronic fatigue syndrome is an often frustrating condition for which up until now only two interventions have been shown beneficial: cognitive behavioral therapy and graded exercise training.

The randomized trial included 154 patients aged 18-55 years with unexplained chronic fatigue of at least 6 months duration plus multiple other findings consistent with the Centers for Disease Control and Prevention definition of chronic fatigue syndrome. While participants met criteria for the syndrome, most of them did not carry a formal physician diagnosis, and thus would most accurately be said to have chronic fatigue syndrome–like illness, she noted.

Subjects were randomized to two group qigong sessions per week for 5 weeks, with each session lasting 2 hours, along with a recommended 15-30 minutes per day of practice at home, or to a wait-list control group. This was wu xing ping heng gong–style qigong. The movements, consisting of 10 forms, were typically performed in the morning, whereas the meditation was done at night before going to sleep. The focus of the meditation was simply on diaphragmatic breathing.

The primary study end point was change in the 14-item Chalder Fatigue Scale from baseline through 5 weeks of qigong. Subjects in the qigong arm demonstrated a 39% reduction in their total score, while scores in the control arm didn’t change significantly (39.7 vs. 24.4 in the quigong arm compared with 39.8 vs. 34.1 in the control arm). The qigong group also displayed significant improvements in the Short Form-12 physical and mental component scores and the Body-Mind-Spirit Integrative Well-Being score (see chart).

Many patients found the full qigong regimen too arduous or time consuming. Those who practiced qigong at least three times per week and spent an average of 30 minutes or more per session showed nearly twice as great an improvement in Chalder scores as those who did less.

The trial was sponsored by the University of Hong Kong Center on Behavioral Health. Ms. Chan reported having no financial conflicts.

NEW ORLEANS – The traditional Chinese medical therapy known as quigong exercise resulted in significant reduction in fatigue scores in patients with chronic fatigue syndrome in a randomized controlled trial.

Qigong also led to significant improvement in validated measures of mental and physical health and spiritual well-being, Jessie S.M. Chan reported at the annual meeting of the Society of Behavioral Medicine.

Photo ©Anna Furman/iStockphoto.com

A dose-response effect was evident. Practicing qigong for at least 30 minutes on at least 3 days per week produced better outcomes, according to Ms. Chan, a doctoral candidate at the University of Hong Kong.

Qigong, translated as "life energy cultivation," is an ancient Taoist art of self-healing. It’s an increasingly popular form of complementary and alternative medicine in the United States. It combines regulation of the body, mind, and breath through a program of gentle exercises and meditation.

From a traditional Chinese medicine perspective, Ms. Chan explained, chronic fatigue syndrome is caused by blood stasis due to a deficiency of Qi, or vital energy. The key treatment strategy entails restoring the balance between yin and yang and stimulation of the blood to get the Qi circulating.

From the perspective of the busy Western primary care physician, of course, chronic fatigue syndrome is an often frustrating condition for which up until now only two interventions have been shown beneficial: cognitive behavioral therapy and graded exercise training.

The randomized trial included 154 patients aged 18-55 years with unexplained chronic fatigue of at least 6 months duration plus multiple other findings consistent with the Centers for Disease Control and Prevention definition of chronic fatigue syndrome. While participants met criteria for the syndrome, most of them did not carry a formal physician diagnosis, and thus would most accurately be said to have chronic fatigue syndrome–like illness, she noted.

Subjects were randomized to two group qigong sessions per week for 5 weeks, with each session lasting 2 hours, along with a recommended 15-30 minutes per day of practice at home, or to a wait-list control group. This was wu xing ping heng gong–style qigong. The movements, consisting of 10 forms, were typically performed in the morning, whereas the meditation was done at night before going to sleep. The focus of the meditation was simply on diaphragmatic breathing.

The primary study end point was change in the 14-item Chalder Fatigue Scale from baseline through 5 weeks of qigong. Subjects in the qigong arm demonstrated a 39% reduction in their total score, while scores in the control arm didn’t change significantly (39.7 vs. 24.4 in the quigong arm compared with 39.8 vs. 34.1 in the control arm). The qigong group also displayed significant improvements in the Short Form-12 physical and mental component scores and the Body-Mind-Spirit Integrative Well-Being score (see chart).

Many patients found the full qigong regimen too arduous or time consuming. Those who practiced qigong at least three times per week and spent an average of 30 minutes or more per session showed nearly twice as great an improvement in Chalder scores as those who did less.

The trial was sponsored by the University of Hong Kong Center on Behavioral Health. Ms. Chan reported having no financial conflicts.

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – The interleukin-17 blocker ixekizumab demonstrated significant clinical benefit and noteworthy rapid onset of efficacy in a phase II clinical trial in rheumatoid arthritis patients.

The anti-IL-17 monoclonal antibody proved effective both in patients naive to biologic therapy and in prior inadequate responders to tumor necrosis factor (TNF) inhibitors, reported Dr. Mark Genovese, who is professor of medicine at Stanford (Calif.) University.

"We saw ACR 20 responses and DAS28 and C-reactive protein values decrease within 3 days," he observed.

The randomized, double-blind study included 260 biologic-naive subjects and 188 others with an inadequate response to one or more TNF inhibitors. The biologic-naive patients were randomized to subcutaneous ixekizumab at 3, 10, 30, 80, or 180 mg at weeks 0, 1, 2, and every 2 weeks thereafter or to placebo. The TNF inhibitor–refractory patients received ixekizumab at 80 or 180 mg or placebo on the same dosing schedule. Everyone also received methotrexate or another nonbiologic disease-modifying antirheumatic drug.

The prespecified primary end point required by the Food and Drug Administration was the ACR 20 response at week 12. Although all patients in the biologic-naive group had higher ACR 20 response rates than did the placebo-treated controls, there was no clear dose-response effect. Only in subjects on ixekizumab at 30 mg did the difference from placebo attain statistical significance; their ACR 20 rate of 70% was twice than in controls.

In patients with prior inadequate response to anti-TNF agents, both the 80- and 180-mg doses of the anti-IL-17 biologic resulted in ACR 20 response rates of about 40%, roughly twice the rate with placebo.

For the secondary end points of Disease Activity Score based on 28-joint counts (DAS28), Clinical Disease Activity Index, and C-reactive protein titers, moderate to good responses were seen at multiple doses. For example, mean CRP levels remained essentially unchanged over time in the placebo group but dropped by 10.2-11.0 mg/L from a baseline of about 20 mg/L in biologic-naive patients on 30, 80, or 180 mg of ixekizumab. Mean CRP dropped by 5.7 and 8.1 mg/L, respectively, in patients with prior inadequate response to anti-TNF therapy who were assigned to ixekizumab at 80 and 180 mg.

Asked later about the somewhat muddy ACR 20 findings, Dr. Genovese replied, "This isn’t the only trial to date that’s been able to show a much nicer dose-response curve with DAS28 as opposed to ACR 20. While it’s only my personal opinion, it appears to me that the DAS scoring system seems to be a more robust and clinically applicable scoring system for use in outcomes in a dose-response study."

Ixekizumab’s safety profile in the phase II study was "comparable to other biologic therapies," the rheumatologist continued. Attrition was low, with only three treatment discontinuations because of adverse events in the active-treatment arm. Serious treatment-emergent adverse events occurred in 1.7% of controls and 4% of patients on the IL-17 inhibitor. Upper respiratory and urinary tract infections were slightly more frequent in ixekizumab-treated patients; however, no mycobacterial or systemic fungal infections occurred. Neutrophil counts were modestly lower in the ixekizumab group but were unrelated to infection risk.

Dr. Genovese reported receiving research grants from and serving as a consultant to Eli Lilly, which is developing ixekizumab for treatment of rheumatoid arthritis and psoriasis.

BERLIN – The interleukin-17 blocker ixekizumab demonstrated significant clinical benefit and noteworthy rapid onset of efficacy in a phase II clinical trial in rheumatoid arthritis patients.

The anti-IL-17 monoclonal antibody proved effective both in patients naive to biologic therapy and in prior inadequate responders to tumor necrosis factor (TNF) inhibitors, reported Dr. Mark Genovese, who is professor of medicine at Stanford (Calif.) University.

"We saw ACR 20 responses and DAS28 and C-reactive protein values decrease within 3 days," he observed.

The randomized, double-blind study included 260 biologic-naive subjects and 188 others with an inadequate response to one or more TNF inhibitors. The biologic-naive patients were randomized to subcutaneous ixekizumab at 3, 10, 30, 80, or 180 mg at weeks 0, 1, 2, and every 2 weeks thereafter or to placebo. The TNF inhibitor–refractory patients received ixekizumab at 80 or 180 mg or placebo on the same dosing schedule. Everyone also received methotrexate or another nonbiologic disease-modifying antirheumatic drug.

The prespecified primary end point required by the Food and Drug Administration was the ACR 20 response at week 12. Although all patients in the biologic-naive group had higher ACR 20 response rates than did the placebo-treated controls, there was no clear dose-response effect. Only in subjects on ixekizumab at 30 mg did the difference from placebo attain statistical significance; their ACR 20 rate of 70% was twice than in controls.

In patients with prior inadequate response to anti-TNF agents, both the 80- and 180-mg doses of the anti-IL-17 biologic resulted in ACR 20 response rates of about 40%, roughly twice the rate with placebo.

For the secondary end points of Disease Activity Score based on 28-joint counts (DAS28), Clinical Disease Activity Index, and C-reactive protein titers, moderate to good responses were seen at multiple doses. For example, mean CRP levels remained essentially unchanged over time in the placebo group but dropped by 10.2-11.0 mg/L from a baseline of about 20 mg/L in biologic-naive patients on 30, 80, or 180 mg of ixekizumab. Mean CRP dropped by 5.7 and 8.1 mg/L, respectively, in patients with prior inadequate response to anti-TNF therapy who were assigned to ixekizumab at 80 and 180 mg.

Asked later about the somewhat muddy ACR 20 findings, Dr. Genovese replied, "This isn’t the only trial to date that’s been able to show a much nicer dose-response curve with DAS28 as opposed to ACR 20. While it’s only my personal opinion, it appears to me that the DAS scoring system seems to be a more robust and clinically applicable scoring system for use in outcomes in a dose-response study."

Ixekizumab’s safety profile in the phase II study was "comparable to other biologic therapies," the rheumatologist continued. Attrition was low, with only three treatment discontinuations because of adverse events in the active-treatment arm. Serious treatment-emergent adverse events occurred in 1.7% of controls and 4% of patients on the IL-17 inhibitor. Upper respiratory and urinary tract infections were slightly more frequent in ixekizumab-treated patients; however, no mycobacterial or systemic fungal infections occurred. Neutrophil counts were modestly lower in the ixekizumab group but were unrelated to infection risk.

Dr. Genovese reported receiving research grants from and serving as a consultant to Eli Lilly, which is developing ixekizumab for treatment of rheumatoid arthritis and psoriasis.

BERLIN – The interleukin-17 blocker ixekizumab demonstrated significant clinical benefit and noteworthy rapid onset of efficacy in a phase II clinical trial in rheumatoid arthritis patients.

The anti-IL-17 monoclonal antibody proved effective both in patients naive to biologic therapy and in prior inadequate responders to tumor necrosis factor (TNF) inhibitors, reported Dr. Mark Genovese, who is professor of medicine at Stanford (Calif.) University.

"We saw ACR 20 responses and DAS28 and C-reactive protein values decrease within 3 days," he observed.

The randomized, double-blind study included 260 biologic-naive subjects and 188 others with an inadequate response to one or more TNF inhibitors. The biologic-naive patients were randomized to subcutaneous ixekizumab at 3, 10, 30, 80, or 180 mg at weeks 0, 1, 2, and every 2 weeks thereafter or to placebo. The TNF inhibitor–refractory patients received ixekizumab at 80 or 180 mg or placebo on the same dosing schedule. Everyone also received methotrexate or another nonbiologic disease-modifying antirheumatic drug.

The prespecified primary end point required by the Food and Drug Administration was the ACR 20 response at week 12. Although all patients in the biologic-naive group had higher ACR 20 response rates than did the placebo-treated controls, there was no clear dose-response effect. Only in subjects on ixekizumab at 30 mg did the difference from placebo attain statistical significance; their ACR 20 rate of 70% was twice than in controls.

In patients with prior inadequate response to anti-TNF agents, both the 80- and 180-mg doses of the anti-IL-17 biologic resulted in ACR 20 response rates of about 40%, roughly twice the rate with placebo.

For the secondary end points of Disease Activity Score based on 28-joint counts (DAS28), Clinical Disease Activity Index, and C-reactive protein titers, moderate to good responses were seen at multiple doses. For example, mean CRP levels remained essentially unchanged over time in the placebo group but dropped by 10.2-11.0 mg/L from a baseline of about 20 mg/L in biologic-naive patients on 30, 80, or 180 mg of ixekizumab. Mean CRP dropped by 5.7 and 8.1 mg/L, respectively, in patients with prior inadequate response to anti-TNF therapy who were assigned to ixekizumab at 80 and 180 mg.

Asked later about the somewhat muddy ACR 20 findings, Dr. Genovese replied, "This isn’t the only trial to date that’s been able to show a much nicer dose-response curve with DAS28 as opposed to ACR 20. While it’s only my personal opinion, it appears to me that the DAS scoring system seems to be a more robust and clinically applicable scoring system for use in outcomes in a dose-response study."

Ixekizumab’s safety profile in the phase II study was "comparable to other biologic therapies," the rheumatologist continued. Attrition was low, with only three treatment discontinuations because of adverse events in the active-treatment arm. Serious treatment-emergent adverse events occurred in 1.7% of controls and 4% of patients on the IL-17 inhibitor. Upper respiratory and urinary tract infections were slightly more frequent in ixekizumab-treated patients; however, no mycobacterial or systemic fungal infections occurred. Neutrophil counts were modestly lower in the ixekizumab group but were unrelated to infection risk.

Dr. Genovese reported receiving research grants from and serving as a consultant to Eli Lilly, which is developing ixekizumab for treatment of rheumatoid arthritis and psoriasis.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

NEW ORLEANS – Suspect a problem with the hemoglobin A_1c whenever it’s discordant with blood sugar–monitoring data.

This happens surprisingly often. The HbA_1c level is a measure of glycolated hemoglobin, so any condition that affects hemoglobin, either qualitatively or quantitatively, can seriously distort the HbA_1c value, Dr. Thomas L. O’Connell explained at the annual meeting of the American College of Physicians.

Examples include patients on hemodialysis, or who have recently been transfused, are anemic, or who have a hemoglobinopathy, noted Dr. O’Connell, an endocrinologist at Duke University, Durham, N.C.

"Don’t even bother measuring [HbA_1c] in a patient who has recently been transfused. This happens all the time in the hospital: a transfused patient’s blood sugar level on finger-stick testing is 300 mg/dL, but the [HbA_1c] is 5.5%," he observed.

Hemoglobinopathies can result in either a false-high or false-low HbA_1c value. More than 700 hemoglobinopathies or abnormal hemoglobin variants have been described and many of these are asymptomatic. The most common hemoglobinopathy in the United States is sickle cell trait, affecting 2 million people.

"There are a lot of people out there with hemoglobinopathies," the endocrinologist stressed.

When the HbA_1c results seem sketchy, an excellent alternative is the fructosamine test. Not nearly as well known as the HbA_1c, the fructosamine test measures glycolated protein in the blood rather than glycolated hemoglobin, so it is unaffected by hemoglobinopathies.

If blood glucose measurement by fingerstick provides a snapshot of a patient’s diabetic control and the HbA_1c is more like a feature-length movie reflecting metabolic control over the past 3 months, then the fructosamine test is akin to a short film providing a view of a patient’s average blood glucose concentration during the previous 2-3 weeks.

Dr. O’Connell reported that he serves as a consultant to Sanofi-Aventis and Amylin.

NEW ORLEANS – Suspect a problem with the hemoglobin A_1c whenever it’s discordant with blood sugar–monitoring data.

This happens surprisingly often. The HbA_1c level is a measure of glycolated hemoglobin, so any condition that affects hemoglobin, either qualitatively or quantitatively, can seriously distort the HbA_1c value, Dr. Thomas L. O’Connell explained at the annual meeting of the American College of Physicians.

Examples include patients on hemodialysis, or who have recently been transfused, are anemic, or who have a hemoglobinopathy, noted Dr. O’Connell, an endocrinologist at Duke University, Durham, N.C.

"Don’t even bother measuring [HbA_1c] in a patient who has recently been transfused. This happens all the time in the hospital: a transfused patient’s blood sugar level on finger-stick testing is 300 mg/dL, but the [HbA_1c] is 5.5%," he observed.

Hemoglobinopathies can result in either a false-high or false-low HbA_1c value. More than 700 hemoglobinopathies or abnormal hemoglobin variants have been described and many of these are asymptomatic. The most common hemoglobinopathy in the United States is sickle cell trait, affecting 2 million people.

"There are a lot of people out there with hemoglobinopathies," the endocrinologist stressed.

When the HbA_1c results seem sketchy, an excellent alternative is the fructosamine test. Not nearly as well known as the HbA_1c, the fructosamine test measures glycolated protein in the blood rather than glycolated hemoglobin, so it is unaffected by hemoglobinopathies.

If blood glucose measurement by fingerstick provides a snapshot of a patient’s diabetic control and the HbA_1c is more like a feature-length movie reflecting metabolic control over the past 3 months, then the fructosamine test is akin to a short film providing a view of a patient’s average blood glucose concentration during the previous 2-3 weeks.

Dr. O’Connell reported that he serves as a consultant to Sanofi-Aventis and Amylin.

NEW ORLEANS – Suspect a problem with the hemoglobin A_1c whenever it’s discordant with blood sugar–monitoring data.

This happens surprisingly often. The HbA_1c level is a measure of glycolated hemoglobin, so any condition that affects hemoglobin, either qualitatively or quantitatively, can seriously distort the HbA_1c value, Dr. Thomas L. O’Connell explained at the annual meeting of the American College of Physicians.

Examples include patients on hemodialysis, or who have recently been transfused, are anemic, or who have a hemoglobinopathy, noted Dr. O’Connell, an endocrinologist at Duke University, Durham, N.C.

"Don’t even bother measuring [HbA_1c] in a patient who has recently been transfused. This happens all the time in the hospital: a transfused patient’s blood sugar level on finger-stick testing is 300 mg/dL, but the [HbA_1c] is 5.5%," he observed.

Hemoglobinopathies can result in either a false-high or false-low HbA_1c value. More than 700 hemoglobinopathies or abnormal hemoglobin variants have been described and many of these are asymptomatic. The most common hemoglobinopathy in the United States is sickle cell trait, affecting 2 million people.

"There are a lot of people out there with hemoglobinopathies," the endocrinologist stressed.

When the HbA_1c results seem sketchy, an excellent alternative is the fructosamine test. Not nearly as well known as the HbA_1c, the fructosamine test measures glycolated protein in the blood rather than glycolated hemoglobin, so it is unaffected by hemoglobinopathies.

If blood glucose measurement by fingerstick provides a snapshot of a patient’s diabetic control and the HbA_1c is more like a feature-length movie reflecting metabolic control over the past 3 months, then the fructosamine test is akin to a short film providing a view of a patient’s average blood glucose concentration during the previous 2-3 weeks.

Dr. O’Connell reported that he serves as a consultant to Sanofi-Aventis and Amylin.

RALEIGH, N.C. – Punch incision epidermal inclusion cysts located on the trunk leaves a significantly smaller scar than does elliptical excision with a similarly low recurrence rate, according to the results of a randomized trail.

Procedure time was essentially the same for the two techniques, at around 13 minutes. Although punch incision and its wound closure can be easier, it took a fair amount of time to squeeze the cyst contents through the small punch opening and remove the cyst lining using a curette, Dr. Justin T. Cheeley explained at the annual meeting of the Society for Investigative Dermatology.

He reported on 40 consecutive patients with one or more truncal epidermal inclusion cysts 1-3 cm in diameter who were randomized to elliptical excision or punch incision in a head-to-head comparative trial.

The primary study end point – cyst recurrence during 16 months of prospective follow-up – occurred in three patients in the punch incision group and two in the elliptical excision group. Predictors of cyst recurrence were sought, but none could be identified, according to Dr. Cheeley of Emory University, Atlanta.

Most secondary end points were similar for the two study arms, including early and late complication rates, as well as improvement in skin-specific quality of life and patient satisfaction as measured by change in Skindex-16 scores.

There was, however, a significant difference between the two study groups in terms of average scar length. In the punch incision group, average scar length was 1.1 cm, compared with 1.8 cm in the elliptical excision group.

The investigators employed a 4-mm punch for the most part, although they turned to a 6-mm punch in treating larger cysts. Punch incision wounds were closed with a single nylon suture. Closure of the elliptical excision sites required more extensive suturing.

Audience member Dr. Eric L. Simpson complimented Dr. Cheeley and his coinvestigators for conducting a study with important cost implications given how often epidermal inclusion cysts are encountered in practice.

“The difference between punch incision and elliptical excision with an intermediate-level repair is probably 10-fold in terms of cost,” said Dr. Simpson of Oregon Health and Science University, Portland.

Dr. Cheeley reported having no financial conflicts.

RALEIGH, N.C. – Punch incision epidermal inclusion cysts located on the trunk leaves a significantly smaller scar than does elliptical excision with a similarly low recurrence rate, according to the results of a randomized trail.

Procedure time was essentially the same for the two techniques, at around 13 minutes. Although punch incision and its wound closure can be easier, it took a fair amount of time to squeeze the cyst contents through the small punch opening and remove the cyst lining using a curette, Dr. Justin T. Cheeley explained at the annual meeting of the Society for Investigative Dermatology.

He reported on 40 consecutive patients with one or more truncal epidermal inclusion cysts 1-3 cm in diameter who were randomized to elliptical excision or punch incision in a head-to-head comparative trial.

The primary study end point – cyst recurrence during 16 months of prospective follow-up – occurred in three patients in the punch incision group and two in the elliptical excision group. Predictors of cyst recurrence were sought, but none could be identified, according to Dr. Cheeley of Emory University, Atlanta.

Most secondary end points were similar for the two study arms, including early and late complication rates, as well as improvement in skin-specific quality of life and patient satisfaction as measured by change in Skindex-16 scores.

There was, however, a significant difference between the two study groups in terms of average scar length. In the punch incision group, average scar length was 1.1 cm, compared with 1.8 cm in the elliptical excision group.

The investigators employed a 4-mm punch for the most part, although they turned to a 6-mm punch in treating larger cysts. Punch incision wounds were closed with a single nylon suture. Closure of the elliptical excision sites required more extensive suturing.

Audience member Dr. Eric L. Simpson complimented Dr. Cheeley and his coinvestigators for conducting a study with important cost implications given how often epidermal inclusion cysts are encountered in practice.

“The difference between punch incision and elliptical excision with an intermediate-level repair is probably 10-fold in terms of cost,” said Dr. Simpson of Oregon Health and Science University, Portland.

Dr. Cheeley reported having no financial conflicts.

RALEIGH, N.C. – Punch incision epidermal inclusion cysts located on the trunk leaves a significantly smaller scar than does elliptical excision with a similarly low recurrence rate, according to the results of a randomized trail.

Procedure time was essentially the same for the two techniques, at around 13 minutes. Although punch incision and its wound closure can be easier, it took a fair amount of time to squeeze the cyst contents through the small punch opening and remove the cyst lining using a curette, Dr. Justin T. Cheeley explained at the annual meeting of the Society for Investigative Dermatology.

He reported on 40 consecutive patients with one or more truncal epidermal inclusion cysts 1-3 cm in diameter who were randomized to elliptical excision or punch incision in a head-to-head comparative trial.

The primary study end point – cyst recurrence during 16 months of prospective follow-up – occurred in three patients in the punch incision group and two in the elliptical excision group. Predictors of cyst recurrence were sought, but none could be identified, according to Dr. Cheeley of Emory University, Atlanta.

Most secondary end points were similar for the two study arms, including early and late complication rates, as well as improvement in skin-specific quality of life and patient satisfaction as measured by change in Skindex-16 scores.

There was, however, a significant difference between the two study groups in terms of average scar length. In the punch incision group, average scar length was 1.1 cm, compared with 1.8 cm in the elliptical excision group.

The investigators employed a 4-mm punch for the most part, although they turned to a 6-mm punch in treating larger cysts. Punch incision wounds were closed with a single nylon suture. Closure of the elliptical excision sites required more extensive suturing.

Audience member Dr. Eric L. Simpson complimented Dr. Cheeley and his coinvestigators for conducting a study with important cost implications given how often epidermal inclusion cysts are encountered in practice.

“The difference between punch incision and elliptical excision with an intermediate-level repair is probably 10-fold in terms of cost,” said Dr. Simpson of Oregon Health and Science University, Portland.

Dr. Cheeley reported having no financial conflicts.