Rheumatoid Arthritis

VIENNA — The expanding universe of targeted cytokine therapy for autoimmune disease now includes anti-interferon-γ with results of a small, double-blind study suggesting equal efficacy compared with anti-tumor-necrosis factor-α treatment in refractory rheumatoid arthritis (RA).

The trial included 55 patients who had failed previous treatment with at least one disease-modifying antirheumatic drug. The patients were randomly assigned to receive five intramuscular injections of anti-interferon-γ (20 patients), anti-tumor necrosis factor-α (20 patients), or placebo (15 patients), Galina V. Lukina, M.D., said at the annual European congress of rheumatology.

A total of 16 patients stopped treatment because of lack of efficacy, 2 of them were in the anti-IFN-γ group, 3 in the anti-TNF-α group, and 11 in the placebo group.

By day 28, the total number of ACR responders was 14 in the anti-IFN-γ group, 11 in the anti-TNF-α group, and zero in the placebo group, said Dr. Lukina of the laboratory of clinical pharmacology at the Institute of Rheumatology, Moscow.

At day 7, three patients in each active treatment group had achieved an American College of Rheumatology (ACR) 70 response.

This number doubled by day 28 in the anti-IFN-γ group, but fell to zero in the anti-TNF-α group. (See chart.)

Also at day 7, significant decreases in serum rheumatoid factor were observed in the anti-IFN-γ group but not in the other two groups, she said at the meeting, which was sponsored by the European League Against Rheumatism.

Synovial ultrasound was performed before and after treatment. Only in the anti-IFN-γ-treated patients was there significant reduction in inflammation of the synovial membrane, she said.

Clinical remission persisted up to 36 months in five patients in each anticytokine group.

“The degree of improvement in patients treated with anti-IFN-γ was comparable with that in patients having received anti-TNF-α and in some aspects was superior to it,” Dr. Lukina said.

These results suggest that IFN-γ plays an important role in the pathogenesis of RA, and inhibition of this cytokine is “a promising approach to the therapy of RA, especially in its refractory forms,” she said.

An ultrasound of the synovial membrane is shown before treatment.

After anti-interferon therapy, synovial inflammation is significantly reduced. Photos courtesy Dr. Galina V. Lukina

VIENNA — The expanding universe of targeted cytokine therapy for autoimmune disease now includes anti-interferon-γ with results of a small, double-blind study suggesting equal efficacy compared with anti-tumor-necrosis factor-α treatment in refractory rheumatoid arthritis (RA).

The trial included 55 patients who had failed previous treatment with at least one disease-modifying antirheumatic drug. The patients were randomly assigned to receive five intramuscular injections of anti-interferon-γ (20 patients), anti-tumor necrosis factor-α (20 patients), or placebo (15 patients), Galina V. Lukina, M.D., said at the annual European congress of rheumatology.

A total of 16 patients stopped treatment because of lack of efficacy, 2 of them were in the anti-IFN-γ group, 3 in the anti-TNF-α group, and 11 in the placebo group.

By day 28, the total number of ACR responders was 14 in the anti-IFN-γ group, 11 in the anti-TNF-α group, and zero in the placebo group, said Dr. Lukina of the laboratory of clinical pharmacology at the Institute of Rheumatology, Moscow.

At day 7, three patients in each active treatment group had achieved an American College of Rheumatology (ACR) 70 response.

This number doubled by day 28 in the anti-IFN-γ group, but fell to zero in the anti-TNF-α group. (See chart.)

Also at day 7, significant decreases in serum rheumatoid factor were observed in the anti-IFN-γ group but not in the other two groups, she said at the meeting, which was sponsored by the European League Against Rheumatism.

Synovial ultrasound was performed before and after treatment. Only in the anti-IFN-γ-treated patients was there significant reduction in inflammation of the synovial membrane, she said.

Clinical remission persisted up to 36 months in five patients in each anticytokine group.

“The degree of improvement in patients treated with anti-IFN-γ was comparable with that in patients having received anti-TNF-α and in some aspects was superior to it,” Dr. Lukina said.

These results suggest that IFN-γ plays an important role in the pathogenesis of RA, and inhibition of this cytokine is “a promising approach to the therapy of RA, especially in its refractory forms,” she said.

An ultrasound of the synovial membrane is shown before treatment.

After anti-interferon therapy, synovial inflammation is significantly reduced. Photos courtesy Dr. Galina V. Lukina

VIENNA — The expanding universe of targeted cytokine therapy for autoimmune disease now includes anti-interferon-γ with results of a small, double-blind study suggesting equal efficacy compared with anti-tumor-necrosis factor-α treatment in refractory rheumatoid arthritis (RA).

The trial included 55 patients who had failed previous treatment with at least one disease-modifying antirheumatic drug. The patients were randomly assigned to receive five intramuscular injections of anti-interferon-γ (20 patients), anti-tumor necrosis factor-α (20 patients), or placebo (15 patients), Galina V. Lukina, M.D., said at the annual European congress of rheumatology.

A total of 16 patients stopped treatment because of lack of efficacy, 2 of them were in the anti-IFN-γ group, 3 in the anti-TNF-α group, and 11 in the placebo group.

By day 28, the total number of ACR responders was 14 in the anti-IFN-γ group, 11 in the anti-TNF-α group, and zero in the placebo group, said Dr. Lukina of the laboratory of clinical pharmacology at the Institute of Rheumatology, Moscow.

At day 7, three patients in each active treatment group had achieved an American College of Rheumatology (ACR) 70 response.

This number doubled by day 28 in the anti-IFN-γ group, but fell to zero in the anti-TNF-α group. (See chart.)

Also at day 7, significant decreases in serum rheumatoid factor were observed in the anti-IFN-γ group but not in the other two groups, she said at the meeting, which was sponsored by the European League Against Rheumatism.

Synovial ultrasound was performed before and after treatment. Only in the anti-IFN-γ-treated patients was there significant reduction in inflammation of the synovial membrane, she said.

Clinical remission persisted up to 36 months in five patients in each anticytokine group.

“The degree of improvement in patients treated with anti-IFN-γ was comparable with that in patients having received anti-TNF-α and in some aspects was superior to it,” Dr. Lukina said.

These results suggest that IFN-γ plays an important role in the pathogenesis of RA, and inhibition of this cytokine is “a promising approach to the therapy of RA, especially in its refractory forms,” she said.

An ultrasound of the synovial membrane is shown before treatment.

After anti-interferon therapy, synovial inflammation is significantly reduced. Photos courtesy Dr. Galina V. Lukina

SANTA BARBARA, CALIF. — Deposition of calcium pyrophosphate dihydrate into joints can mimic several other conditions, including osteoarthritis, rheumatoid arthritis, and gout, and making a definitive diagnosis can be quite a challenge, Ann K. Rosenthal, M.D., said at a symposium sponsored by the American College of Rheumatology.

A definitive diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease can be made only by identifying the crystals directly, using complex techniques such as x-ray diffraction or Fourier transform infrared spectroscopy, techniques that are unavailable in most clinical labs.

“Most of us diagnose CPPD deposition by synovial analysis,” said Dr. Rosenthal of the Medical College of Wisconsin, Milwaukee. “We look under polarizing light microscopy and see the positively birefringent crystals. This really remains the gold standard clinically.”

Unfortunately, CPPD crystals are often only weakly birefringent, with one study indicating that just 17%–40% of the crystals glow under polarizing light (Ann. Rheum. Dis. 1999;58:582–4). In contrast, practically all gout crystals are birefringent. For this reason, nonpolarizing light microscopy may be useful in diagnosing CPPD deposition disease.

The disease is such an excellent imitator of other rheumatic conditions that many physicians never suspect calcium crystals as a cause. In all likelihood, many cases are missed because of poor diagnostic techniques.

An analysis of a patient's risk factors for CPPD deposition disease provides little ammunition to increase the index of suspicion.

The condition is rare in people under the age of 60 but rapidly increases in incidence in older patients. About 50% of patients over the age of 90 have radiographic evidence of CPPD deposition. Women are slightly more likely than men to have CPPD deposition. And prior injury to the joint increases the risk of CPPD deposition.

A variety of metabolic disorders are associated with the formation of CPPD crystals. The most significant are hyperparathyroidism, hemochromatosis, hypomagnesemia, and gout, but case reports have implicated a number of other conditions.

The clinical presentation of CPPD-induced pseudogout, pseudo-rheumatoid arthritis, or pseudoosteoarthritis can differ in subtle ways from the true conditions. For example, pseudoosteoarthritis (the most common CPPD deposition disease) can appear identical to true osteoarthritis, although it may affect unusual joints.

“Perhaps a lot of what we're calling osteoarthritis is actually CPPD deposition disease,” Dr. Rosenthal said. One study demonstrated a 60% prevalence of either CPPD or basic calcium phosphate crystals (called BCP crystals or hydroxyapatite) in knee joints of patients with a preoperative diagnosis of osteoarthritis (J. Rheumatol. 2002;29:570–4).

Chondrocalcinosis is the radiographic hallmark of CPPD deposition disease, but it can be risky to diagnose the condition based on radiographic findings alone, Dr. Rosenthal said. Chondrocalcinosis appears as a linear deposition of calcium, often in the fibrocartilage or lining of the articular cartilage. It is most likely to be found in the symphysis pubis and the triangular cartilage of the wrist.

Ultrasound is the most promising new technique for CPPD diagnosis, with a recent study identifying three patterns that appear highly specific for CPPD deposition disease. The first is a punctate pattern with several thin hyperechoic spots in fibrocartilage and tendons. The second is characterized by homogeneous hyperechoic or oval deposits localized in bursae and articular recesses. The third pattern shows thin hyperechoic bands parallel to the articular surfaces (Ann. Rheum. Dis. 2005;64:638–40).

MRI adds little to a diagnosis, since calcification in cartilage can appear as high or low signal intensity.

On the other hand, CT scans can be quite sensitive and may be particularly useful for cases with spinal involvement. One advantage of CT scanning is that the technique can detect—and in some cases differentiate between—both BCP and CPPD crystals.

CPPD crystals are weakly birefringent under polarizing light microscopy (as shown). Only 17%–40% of CPPD crystals glow using such means.

SANTA BARBARA, CALIF. — Deposition of calcium pyrophosphate dihydrate into joints can mimic several other conditions, including osteoarthritis, rheumatoid arthritis, and gout, and making a definitive diagnosis can be quite a challenge, Ann K. Rosenthal, M.D., said at a symposium sponsored by the American College of Rheumatology.

A definitive diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease can be made only by identifying the crystals directly, using complex techniques such as x-ray diffraction or Fourier transform infrared spectroscopy, techniques that are unavailable in most clinical labs.

“Most of us diagnose CPPD deposition by synovial analysis,” said Dr. Rosenthal of the Medical College of Wisconsin, Milwaukee. “We look under polarizing light microscopy and see the positively birefringent crystals. This really remains the gold standard clinically.”

Unfortunately, CPPD crystals are often only weakly birefringent, with one study indicating that just 17%–40% of the crystals glow under polarizing light (Ann. Rheum. Dis. 1999;58:582–4). In contrast, practically all gout crystals are birefringent. For this reason, nonpolarizing light microscopy may be useful in diagnosing CPPD deposition disease.

The disease is such an excellent imitator of other rheumatic conditions that many physicians never suspect calcium crystals as a cause. In all likelihood, many cases are missed because of poor diagnostic techniques.

An analysis of a patient's risk factors for CPPD deposition disease provides little ammunition to increase the index of suspicion.

The condition is rare in people under the age of 60 but rapidly increases in incidence in older patients. About 50% of patients over the age of 90 have radiographic evidence of CPPD deposition. Women are slightly more likely than men to have CPPD deposition. And prior injury to the joint increases the risk of CPPD deposition.

A variety of metabolic disorders are associated with the formation of CPPD crystals. The most significant are hyperparathyroidism, hemochromatosis, hypomagnesemia, and gout, but case reports have implicated a number of other conditions.

The clinical presentation of CPPD-induced pseudogout, pseudo-rheumatoid arthritis, or pseudoosteoarthritis can differ in subtle ways from the true conditions. For example, pseudoosteoarthritis (the most common CPPD deposition disease) can appear identical to true osteoarthritis, although it may affect unusual joints.

“Perhaps a lot of what we're calling osteoarthritis is actually CPPD deposition disease,” Dr. Rosenthal said. One study demonstrated a 60% prevalence of either CPPD or basic calcium phosphate crystals (called BCP crystals or hydroxyapatite) in knee joints of patients with a preoperative diagnosis of osteoarthritis (J. Rheumatol. 2002;29:570–4).

Chondrocalcinosis is the radiographic hallmark of CPPD deposition disease, but it can be risky to diagnose the condition based on radiographic findings alone, Dr. Rosenthal said. Chondrocalcinosis appears as a linear deposition of calcium, often in the fibrocartilage or lining of the articular cartilage. It is most likely to be found in the symphysis pubis and the triangular cartilage of the wrist.

Ultrasound is the most promising new technique for CPPD diagnosis, with a recent study identifying three patterns that appear highly specific for CPPD deposition disease. The first is a punctate pattern with several thin hyperechoic spots in fibrocartilage and tendons. The second is characterized by homogeneous hyperechoic or oval deposits localized in bursae and articular recesses. The third pattern shows thin hyperechoic bands parallel to the articular surfaces (Ann. Rheum. Dis. 2005;64:638–40).

MRI adds little to a diagnosis, since calcification in cartilage can appear as high or low signal intensity.

On the other hand, CT scans can be quite sensitive and may be particularly useful for cases with spinal involvement. One advantage of CT scanning is that the technique can detect—and in some cases differentiate between—both BCP and CPPD crystals.

CPPD crystals are weakly birefringent under polarizing light microscopy (as shown). Only 17%–40% of CPPD crystals glow using such means.

SANTA BARBARA, CALIF. — Deposition of calcium pyrophosphate dihydrate into joints can mimic several other conditions, including osteoarthritis, rheumatoid arthritis, and gout, and making a definitive diagnosis can be quite a challenge, Ann K. Rosenthal, M.D., said at a symposium sponsored by the American College of Rheumatology.

A definitive diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease can be made only by identifying the crystals directly, using complex techniques such as x-ray diffraction or Fourier transform infrared spectroscopy, techniques that are unavailable in most clinical labs.

“Most of us diagnose CPPD deposition by synovial analysis,” said Dr. Rosenthal of the Medical College of Wisconsin, Milwaukee. “We look under polarizing light microscopy and see the positively birefringent crystals. This really remains the gold standard clinically.”

Unfortunately, CPPD crystals are often only weakly birefringent, with one study indicating that just 17%–40% of the crystals glow under polarizing light (Ann. Rheum. Dis. 1999;58:582–4). In contrast, practically all gout crystals are birefringent. For this reason, nonpolarizing light microscopy may be useful in diagnosing CPPD deposition disease.

The disease is such an excellent imitator of other rheumatic conditions that many physicians never suspect calcium crystals as a cause. In all likelihood, many cases are missed because of poor diagnostic techniques.

An analysis of a patient's risk factors for CPPD deposition disease provides little ammunition to increase the index of suspicion.

The condition is rare in people under the age of 60 but rapidly increases in incidence in older patients. About 50% of patients over the age of 90 have radiographic evidence of CPPD deposition. Women are slightly more likely than men to have CPPD deposition. And prior injury to the joint increases the risk of CPPD deposition.

A variety of metabolic disorders are associated with the formation of CPPD crystals. The most significant are hyperparathyroidism, hemochromatosis, hypomagnesemia, and gout, but case reports have implicated a number of other conditions.

The clinical presentation of CPPD-induced pseudogout, pseudo-rheumatoid arthritis, or pseudoosteoarthritis can differ in subtle ways from the true conditions. For example, pseudoosteoarthritis (the most common CPPD deposition disease) can appear identical to true osteoarthritis, although it may affect unusual joints.

“Perhaps a lot of what we're calling osteoarthritis is actually CPPD deposition disease,” Dr. Rosenthal said. One study demonstrated a 60% prevalence of either CPPD or basic calcium phosphate crystals (called BCP crystals or hydroxyapatite) in knee joints of patients with a preoperative diagnosis of osteoarthritis (J. Rheumatol. 2002;29:570–4).

Chondrocalcinosis is the radiographic hallmark of CPPD deposition disease, but it can be risky to diagnose the condition based on radiographic findings alone, Dr. Rosenthal said. Chondrocalcinosis appears as a linear deposition of calcium, often in the fibrocartilage or lining of the articular cartilage. It is most likely to be found in the symphysis pubis and the triangular cartilage of the wrist.

Ultrasound is the most promising new technique for CPPD diagnosis, with a recent study identifying three patterns that appear highly specific for CPPD deposition disease. The first is a punctate pattern with several thin hyperechoic spots in fibrocartilage and tendons. The second is characterized by homogeneous hyperechoic or oval deposits localized in bursae and articular recesses. The third pattern shows thin hyperechoic bands parallel to the articular surfaces (Ann. Rheum. Dis. 2005;64:638–40).

MRI adds little to a diagnosis, since calcification in cartilage can appear as high or low signal intensity.

On the other hand, CT scans can be quite sensitive and may be particularly useful for cases with spinal involvement. One advantage of CT scanning is that the technique can detect—and in some cases differentiate between—both BCP and CPPD crystals.

CPPD crystals are weakly birefringent under polarizing light microscopy (as shown). Only 17%–40% of CPPD crystals glow using such means.

VIENNA — The rising prevalence of gout being reported in the United States and many other parts of the world constitutes in part an indictment of suboptimal physician management of the disease, Michael Doherty, M.D., said at the annual European congress of rheumatology.

“One of the suggestions from several reports in the literature is that part of the increasing epidemic is due, shamefully, to relative undertreatment of gout,” according to Dr. Doherty, professor of rheumatology at the University of Nottingham, England.

The goal of gout treatment is cure. It's a realistic, achievable goal with the drugs available today. And if this were occurring consistently, the small and sporadic increases in the incidence of gout documented during the 1990s would have little impact on the prevalence of active gout.

“If you have a chronic disorder—for example, osteoarthritis, or badly treated gout—then the disease tends to be present for a long time, and a small increase in incidence will have a very large effect upon prevalence by the end of the time studied,” he observed at the meeting sponsored by the European League Against Rheumatism.

One persuasive piece of epidemiologic evidence that this is in fact what has been happening with gout comes from the U.K. General Practice Research Database, a highly regarded national project in which participating primary care physicians directly enter detailed computerized health data on close to 2 million patients in the United Kingdom.

Dr. Doherty noted that, in a recent report analyzing gout trends in the database for 1990–1999, investigators concluded that the overall annual incidence of gout in the United Kingdom remained relatively stable throughout the decade. In contrast, the prevalence of gout in 1999—estimated at 1.4%, climbing to a peak of 7.3% among men aged 75–84—was nearly threefold greater than in a similar national study conducted in the mid-1970s (Ann. Rheum. Dis. 2005;64:267–72).

Particularly disturbing to Dr. Doherty was the investigators' observation that, consistently during the 1990s, only about 30% of U.K. patients diagnosed with gout were on allopurinol or other hypouricemic therapy aimed at preventing recurrent attacks. This indicates that effective treatment strategies are markedly underused. Moreover, this epidemiologic observation also is supported by everyday clinical experience, which shows that despite a correct diagnosis of gout, many patients continue to have gouty attacks and a progression of their disease, he said.

A rising prevalence of gout has been documented in the United States as well. In a 10-year study of a managed care population with more than 4 million enrollees, investigators concluded that among those ages 75 or older, the disease prevalence climbed from 21/1,000 in 1990 to 41/1,000 in 1999. Among the 65–74 age group, the prevalence rose less dramatically, from 21–24 cases/1,000 in 1990–1992 to more than 31/1,000 in 1997–1999 (J. Rheumatol. 2004;31:1582–7).

While epidemiologic studies have not consistently shown an increase in gout incidence in the 1990s, that's likely to change in the future. Levels of many known gout risk factors are climbing, including some that are related to lifestyle. These include hypertension, obesity, insulin resistance, and dyslipidemia, each an independent risk factor for gout as well as a component of the metabolic syndrome, which has reached epidemic levels in western societies.

Two-thirds of the body's circulating uric acid pool is cleared by the kidneys. Hence the growing incidence and prevalence of renal impairment constitute another rising risk factor for gout.

Advanced age is a powerful gout risk factor. It has been suggested, but is as yet unproved, that part of the explanation lies in the age-related increase in osteoarthritis, since osteoarthritic joint inflammation encourages the deposit of crystals. On the other hand, Dr. Doherty said, there is evidence to suggest a negative correlation between rheumatoid arthritis and gout.

VIENNA — The rising prevalence of gout being reported in the United States and many other parts of the world constitutes in part an indictment of suboptimal physician management of the disease, Michael Doherty, M.D., said at the annual European congress of rheumatology.

“One of the suggestions from several reports in the literature is that part of the increasing epidemic is due, shamefully, to relative undertreatment of gout,” according to Dr. Doherty, professor of rheumatology at the University of Nottingham, England.

The goal of gout treatment is cure. It's a realistic, achievable goal with the drugs available today. And if this were occurring consistently, the small and sporadic increases in the incidence of gout documented during the 1990s would have little impact on the prevalence of active gout.

“If you have a chronic disorder—for example, osteoarthritis, or badly treated gout—then the disease tends to be present for a long time, and a small increase in incidence will have a very large effect upon prevalence by the end of the time studied,” he observed at the meeting sponsored by the European League Against Rheumatism.

One persuasive piece of epidemiologic evidence that this is in fact what has been happening with gout comes from the U.K. General Practice Research Database, a highly regarded national project in which participating primary care physicians directly enter detailed computerized health data on close to 2 million patients in the United Kingdom.

Dr. Doherty noted that, in a recent report analyzing gout trends in the database for 1990–1999, investigators concluded that the overall annual incidence of gout in the United Kingdom remained relatively stable throughout the decade. In contrast, the prevalence of gout in 1999—estimated at 1.4%, climbing to a peak of 7.3% among men aged 75–84—was nearly threefold greater than in a similar national study conducted in the mid-1970s (Ann. Rheum. Dis. 2005;64:267–72).

Particularly disturbing to Dr. Doherty was the investigators' observation that, consistently during the 1990s, only about 30% of U.K. patients diagnosed with gout were on allopurinol or other hypouricemic therapy aimed at preventing recurrent attacks. This indicates that effective treatment strategies are markedly underused. Moreover, this epidemiologic observation also is supported by everyday clinical experience, which shows that despite a correct diagnosis of gout, many patients continue to have gouty attacks and a progression of their disease, he said.

A rising prevalence of gout has been documented in the United States as well. In a 10-year study of a managed care population with more than 4 million enrollees, investigators concluded that among those ages 75 or older, the disease prevalence climbed from 21/1,000 in 1990 to 41/1,000 in 1999. Among the 65–74 age group, the prevalence rose less dramatically, from 21–24 cases/1,000 in 1990–1992 to more than 31/1,000 in 1997–1999 (J. Rheumatol. 2004;31:1582–7).

While epidemiologic studies have not consistently shown an increase in gout incidence in the 1990s, that's likely to change in the future. Levels of many known gout risk factors are climbing, including some that are related to lifestyle. These include hypertension, obesity, insulin resistance, and dyslipidemia, each an independent risk factor for gout as well as a component of the metabolic syndrome, which has reached epidemic levels in western societies.

Two-thirds of the body's circulating uric acid pool is cleared by the kidneys. Hence the growing incidence and prevalence of renal impairment constitute another rising risk factor for gout.

Advanced age is a powerful gout risk factor. It has been suggested, but is as yet unproved, that part of the explanation lies in the age-related increase in osteoarthritis, since osteoarthritic joint inflammation encourages the deposit of crystals. On the other hand, Dr. Doherty said, there is evidence to suggest a negative correlation between rheumatoid arthritis and gout.

VIENNA — The rising prevalence of gout being reported in the United States and many other parts of the world constitutes in part an indictment of suboptimal physician management of the disease, Michael Doherty, M.D., said at the annual European congress of rheumatology.

“One of the suggestions from several reports in the literature is that part of the increasing epidemic is due, shamefully, to relative undertreatment of gout,” according to Dr. Doherty, professor of rheumatology at the University of Nottingham, England.

The goal of gout treatment is cure. It's a realistic, achievable goal with the drugs available today. And if this were occurring consistently, the small and sporadic increases in the incidence of gout documented during the 1990s would have little impact on the prevalence of active gout.

“If you have a chronic disorder—for example, osteoarthritis, or badly treated gout—then the disease tends to be present for a long time, and a small increase in incidence will have a very large effect upon prevalence by the end of the time studied,” he observed at the meeting sponsored by the European League Against Rheumatism.

One persuasive piece of epidemiologic evidence that this is in fact what has been happening with gout comes from the U.K. General Practice Research Database, a highly regarded national project in which participating primary care physicians directly enter detailed computerized health data on close to 2 million patients in the United Kingdom.

Dr. Doherty noted that, in a recent report analyzing gout trends in the database for 1990–1999, investigators concluded that the overall annual incidence of gout in the United Kingdom remained relatively stable throughout the decade. In contrast, the prevalence of gout in 1999—estimated at 1.4%, climbing to a peak of 7.3% among men aged 75–84—was nearly threefold greater than in a similar national study conducted in the mid-1970s (Ann. Rheum. Dis. 2005;64:267–72).

Particularly disturbing to Dr. Doherty was the investigators' observation that, consistently during the 1990s, only about 30% of U.K. patients diagnosed with gout were on allopurinol or other hypouricemic therapy aimed at preventing recurrent attacks. This indicates that effective treatment strategies are markedly underused. Moreover, this epidemiologic observation also is supported by everyday clinical experience, which shows that despite a correct diagnosis of gout, many patients continue to have gouty attacks and a progression of their disease, he said.

A rising prevalence of gout has been documented in the United States as well. In a 10-year study of a managed care population with more than 4 million enrollees, investigators concluded that among those ages 75 or older, the disease prevalence climbed from 21/1,000 in 1990 to 41/1,000 in 1999. Among the 65–74 age group, the prevalence rose less dramatically, from 21–24 cases/1,000 in 1990–1992 to more than 31/1,000 in 1997–1999 (J. Rheumatol. 2004;31:1582–7).

While epidemiologic studies have not consistently shown an increase in gout incidence in the 1990s, that's likely to change in the future. Levels of many known gout risk factors are climbing, including some that are related to lifestyle. These include hypertension, obesity, insulin resistance, and dyslipidemia, each an independent risk factor for gout as well as a component of the metabolic syndrome, which has reached epidemic levels in western societies.

Two-thirds of the body's circulating uric acid pool is cleared by the kidneys. Hence the growing incidence and prevalence of renal impairment constitute another rising risk factor for gout.

Advanced age is a powerful gout risk factor. It has been suggested, but is as yet unproved, that part of the explanation lies in the age-related increase in osteoarthritis, since osteoarthritic joint inflammation encourages the deposit of crystals. On the other hand, Dr. Doherty said, there is evidence to suggest a negative correlation between rheumatoid arthritis and gout.

VIENNA — Response rates to biologic agents are high among patients with rheumatoid arthritis, but remission rates remain disappointingly low, Mikkel Ostergaard, M.D., said at the annual European congress of rheumatology.

According to the Danish Database for Biological Therapies in Rheumatology (DANBIO), two-thirds of patients on tumor necrosis factor-α blockers have persistently inadequate inflammatory control.

A total of 417 patients in Denmark receiving these drugs have been enrolled in DANBIO since October 2000—378 on infliximab and 39 on etanercept. Disease activity was measured at baseline and six times during the following year.

At baseline, the median disease duration was 9 years, swollen joint count was 10, tender joint count was 11, serum C-reactive protein was 27 mcg/mL, and DAS-28 was 5.9.

The median number of disease-modifying antirheumatic drugs taken previously was four.

There were no differences in baseline data or clinical response between patients receiving infliximab and those receiving etanercept.

From week 6 on, 15%–20% of patients were in clinical remission and another 10%–15% had low disease activity. Thus, approximately 70% of patients had moderate or high disease activity, said Dr. Ostergaard of Copenhagen University Hospitals.

Despite this less than optimal response in many patients, the median time they remained on the same drug exceeded 2 years, he said at the congress, sponsored by the European League Against Rheumatism.

This illustrates that continuous close monitoring of each patient with careful consideration of therapeutic adjustments is needed in daily clinical practice to achieve the goal of disease control in RA patients treated with biologics, he said.

Dr. Ostergaard disclosed that he has received financial support from Schering-Plough and Wyeth Pharmaceuticals.

VIENNA — Response rates to biologic agents are high among patients with rheumatoid arthritis, but remission rates remain disappointingly low, Mikkel Ostergaard, M.D., said at the annual European congress of rheumatology.

According to the Danish Database for Biological Therapies in Rheumatology (DANBIO), two-thirds of patients on tumor necrosis factor-α blockers have persistently inadequate inflammatory control.

A total of 417 patients in Denmark receiving these drugs have been enrolled in DANBIO since October 2000—378 on infliximab and 39 on etanercept. Disease activity was measured at baseline and six times during the following year.

At baseline, the median disease duration was 9 years, swollen joint count was 10, tender joint count was 11, serum C-reactive protein was 27 mcg/mL, and DAS-28 was 5.9.

The median number of disease-modifying antirheumatic drugs taken previously was four.

There were no differences in baseline data or clinical response between patients receiving infliximab and those receiving etanercept.

From week 6 on, 15%–20% of patients were in clinical remission and another 10%–15% had low disease activity. Thus, approximately 70% of patients had moderate or high disease activity, said Dr. Ostergaard of Copenhagen University Hospitals.

Despite this less than optimal response in many patients, the median time they remained on the same drug exceeded 2 years, he said at the congress, sponsored by the European League Against Rheumatism.

This illustrates that continuous close monitoring of each patient with careful consideration of therapeutic adjustments is needed in daily clinical practice to achieve the goal of disease control in RA patients treated with biologics, he said.

Dr. Ostergaard disclosed that he has received financial support from Schering-Plough and Wyeth Pharmaceuticals.

VIENNA — Response rates to biologic agents are high among patients with rheumatoid arthritis, but remission rates remain disappointingly low, Mikkel Ostergaard, M.D., said at the annual European congress of rheumatology.

According to the Danish Database for Biological Therapies in Rheumatology (DANBIO), two-thirds of patients on tumor necrosis factor-α blockers have persistently inadequate inflammatory control.

A total of 417 patients in Denmark receiving these drugs have been enrolled in DANBIO since October 2000—378 on infliximab and 39 on etanercept. Disease activity was measured at baseline and six times during the following year.

At baseline, the median disease duration was 9 years, swollen joint count was 10, tender joint count was 11, serum C-reactive protein was 27 mcg/mL, and DAS-28 was 5.9.

The median number of disease-modifying antirheumatic drugs taken previously was four.

There were no differences in baseline data or clinical response between patients receiving infliximab and those receiving etanercept.

From week 6 on, 15%–20% of patients were in clinical remission and another 10%–15% had low disease activity. Thus, approximately 70% of patients had moderate or high disease activity, said Dr. Ostergaard of Copenhagen University Hospitals.

Despite this less than optimal response in many patients, the median time they remained on the same drug exceeded 2 years, he said at the congress, sponsored by the European League Against Rheumatism.

This illustrates that continuous close monitoring of each patient with careful consideration of therapeutic adjustments is needed in daily clinical practice to achieve the goal of disease control in RA patients treated with biologics, he said.

Dr. Ostergaard disclosed that he has received financial support from Schering-Plough and Wyeth Pharmaceuticals.

VIENNA — Transdermal fentanyl brought effective pain relief to patients with advanced knee or hip osteoarthritis in a large randomized, double-blind, placebo-controlled trial, Jozef Vojtassak, M.D., reported at the annual European congress of rheumatology.

Fentanyl patches have previously been shown to be effective for a variety of types of chronic nonmalignant pain, including that associated with osteoarthritis; however, until now the evidence has come largely from open-label studies, according to Dr. Vojtassak of Comenius University, Bratislava, Slovakia.

He reported on 416 patients awaiting knee or hip replacement surgery who were randomized to transdermal fentanyl (Durogesic) or placebo patches in a 6-week double-blind study followed by a week-long taper.

All had previously shown an inadequate response to weak opioids. None had received strong opioids within 4 weeks of enrollment.

The starting dose of fentanyl was 25 mcg/hour. It could gradually be raised to 100 mcg/hour as required. Patches were changed every 72 hours. Allowable supplemental pain medication consisted of nonsteroidal anti-inflammatory agents, used by more than two-thirds of patients, and acetaminophen, used at dosages of up to 4 g/day by 27%.

Of note, 57% of participants withdrew from the study prematurely, with roughly equal numbers of dropouts in both study arms. Their reasons for quitting, however, were quite different. Fifteen patients in the fentanyl arm withdrew because of insufficient treatment efficacy, compared with 66 in the placebo group. On the other hand, 62 patients taking fentanyl quit due to adverse events—chiefly nausea and vomiting—compared with 20 patients in the placebo group, he said at the meeting, which was sponsored by the European League Against Rheumatism.

The primary study end point was change in mean pain visual analog scores recorded by patients in a daily pain diary. From a baseline self-rated score of 73 out of a possible 100, fentanyl-treated patients had a mean 23.4-point decrease, significantly better than the 17.9-point reduction with placebo. Morning and evening pain improved by 19%–20% in the fentanyl arm, compared with a 14% improvement with placebo.

Pain on walking was rated 25% better than at baseline in fentanyl-treated patients with knee osteoarthritis, and 15% better in placebo-treated patients. Similarly, fentanyl-treated patients with hip osteoarthritis rated their pain on walking as 20% improved over baseline, which was significantly better than the nearly 13% improvement among controls.

Measures of functional improvement by the Western Ontario and McMaster Universities Osteoarthritis Index trended strongly in favor of the fentanyl group, a benefit that fell just short of statistical significance.

The study was sponsored by Janssen Pharmaceutica.

VIENNA — Transdermal fentanyl brought effective pain relief to patients with advanced knee or hip osteoarthritis in a large randomized, double-blind, placebo-controlled trial, Jozef Vojtassak, M.D., reported at the annual European congress of rheumatology.

Fentanyl patches have previously been shown to be effective for a variety of types of chronic nonmalignant pain, including that associated with osteoarthritis; however, until now the evidence has come largely from open-label studies, according to Dr. Vojtassak of Comenius University, Bratislava, Slovakia.

He reported on 416 patients awaiting knee or hip replacement surgery who were randomized to transdermal fentanyl (Durogesic) or placebo patches in a 6-week double-blind study followed by a week-long taper.

All had previously shown an inadequate response to weak opioids. None had received strong opioids within 4 weeks of enrollment.

The starting dose of fentanyl was 25 mcg/hour. It could gradually be raised to 100 mcg/hour as required. Patches were changed every 72 hours. Allowable supplemental pain medication consisted of nonsteroidal anti-inflammatory agents, used by more than two-thirds of patients, and acetaminophen, used at dosages of up to 4 g/day by 27%.

Of note, 57% of participants withdrew from the study prematurely, with roughly equal numbers of dropouts in both study arms. Their reasons for quitting, however, were quite different. Fifteen patients in the fentanyl arm withdrew because of insufficient treatment efficacy, compared with 66 in the placebo group. On the other hand, 62 patients taking fentanyl quit due to adverse events—chiefly nausea and vomiting—compared with 20 patients in the placebo group, he said at the meeting, which was sponsored by the European League Against Rheumatism.

The primary study end point was change in mean pain visual analog scores recorded by patients in a daily pain diary. From a baseline self-rated score of 73 out of a possible 100, fentanyl-treated patients had a mean 23.4-point decrease, significantly better than the 17.9-point reduction with placebo. Morning and evening pain improved by 19%–20% in the fentanyl arm, compared with a 14% improvement with placebo.

Pain on walking was rated 25% better than at baseline in fentanyl-treated patients with knee osteoarthritis, and 15% better in placebo-treated patients. Similarly, fentanyl-treated patients with hip osteoarthritis rated their pain on walking as 20% improved over baseline, which was significantly better than the nearly 13% improvement among controls.

Measures of functional improvement by the Western Ontario and McMaster Universities Osteoarthritis Index trended strongly in favor of the fentanyl group, a benefit that fell just short of statistical significance.

The study was sponsored by Janssen Pharmaceutica.

VIENNA — Transdermal fentanyl brought effective pain relief to patients with advanced knee or hip osteoarthritis in a large randomized, double-blind, placebo-controlled trial, Jozef Vojtassak, M.D., reported at the annual European congress of rheumatology.

Fentanyl patches have previously been shown to be effective for a variety of types of chronic nonmalignant pain, including that associated with osteoarthritis; however, until now the evidence has come largely from open-label studies, according to Dr. Vojtassak of Comenius University, Bratislava, Slovakia.

He reported on 416 patients awaiting knee or hip replacement surgery who were randomized to transdermal fentanyl (Durogesic) or placebo patches in a 6-week double-blind study followed by a week-long taper.

All had previously shown an inadequate response to weak opioids. None had received strong opioids within 4 weeks of enrollment.

The starting dose of fentanyl was 25 mcg/hour. It could gradually be raised to 100 mcg/hour as required. Patches were changed every 72 hours. Allowable supplemental pain medication consisted of nonsteroidal anti-inflammatory agents, used by more than two-thirds of patients, and acetaminophen, used at dosages of up to 4 g/day by 27%.

Of note, 57% of participants withdrew from the study prematurely, with roughly equal numbers of dropouts in both study arms. Their reasons for quitting, however, were quite different. Fifteen patients in the fentanyl arm withdrew because of insufficient treatment efficacy, compared with 66 in the placebo group. On the other hand, 62 patients taking fentanyl quit due to adverse events—chiefly nausea and vomiting—compared with 20 patients in the placebo group, he said at the meeting, which was sponsored by the European League Against Rheumatism.

The primary study end point was change in mean pain visual analog scores recorded by patients in a daily pain diary. From a baseline self-rated score of 73 out of a possible 100, fentanyl-treated patients had a mean 23.4-point decrease, significantly better than the 17.9-point reduction with placebo. Morning and evening pain improved by 19%–20% in the fentanyl arm, compared with a 14% improvement with placebo.

Pain on walking was rated 25% better than at baseline in fentanyl-treated patients with knee osteoarthritis, and 15% better in placebo-treated patients. Similarly, fentanyl-treated patients with hip osteoarthritis rated their pain on walking as 20% improved over baseline, which was significantly better than the nearly 13% improvement among controls.

Measures of functional improvement by the Western Ontario and McMaster Universities Osteoarthritis Index trended strongly in favor of the fentanyl group, a benefit that fell just short of statistical significance.

The study was sponsored by Janssen Pharmaceutica.

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European congress of rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told this newspaper.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients. In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected. The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Lateral toe reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European congress of rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told this newspaper.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients. In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected. The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Lateral toe reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka

VIENNA — A new approach to forefoot reconstruction in patients with rheumatoid arthritis has shown superior results with regard to pain, deformity, and function compared with conventional techniques, according to Takeshi Mitsuka, M.D., of the department of orthopedic surgery, Chiba Tokushukai Hospital, Funabashi, Japan.

Reconstruction of the lateral toes is done by means of a metatarsal oblique osteotomy. For the great toe, either a Swanson implant or a metatarsal osteotomy can be done, depending on the condition of the joint, and the result is the preservation of the function of the metatarsophalangeal joints, Dr. Mitsuka wrote in a poster presented at the annual European congress of rheumatology.

“I have been performing this procedure since 1998 for almost all rheumatoid [arthritis] patients with forefoot deformities. The outcome is better than with resection arthroplasty of the MTP [metatarsophalangeal] joints or arthrodesis of the big toe for stability and mobility of the joint, length of toe, gait, and cosmetic result,” he told this newspaper.

A total of 53 forefoot reconstructions in 31 patients have been done to date. Mean age at time of surgery was 60 years, and the mean duration of rheumatoid arthritis until time of operation was 18 years.

At their latest follow-up, patients were evaluated clinically using the American Orthopedic Foot and Ankle Society (AOFAS) score. Hallux valgus angle and intermetatarsal angle were examined radiologically.

Two patients died of causes unrelated to surgery, and in one foot the Swanson implant was removed 11 months after placement because of reactive synovitis.

Among the remaining 48 feet, with a mean follow-up of 40 months, the AOFAS score for the great toe improved from an average of 36 points preoperatively to 89 points (out of 100). For the lateral toes, the average score improved from 27 points to 87 points.

The hallux valgus angle improved from an average of 45 degrees preoperatively to 19 degrees at the latest evaluation, Dr. Mitsuka noted at the meeting, which was sponsored by the European League Against Rheumatism.

Intermetatarsal angle also improved, from an average of 16 degrees before surgery to 13 degrees.

Reconstruction of the great toe of 44 feet in 25 patients involved arthroplasty with a Swanson implant, and was done with a Mitchell's osteotomy in the remaining 9 feet in 6 patients. In the lateral toes, an oblique osteotomy was performed at the metatarsal neck, starting proximally on the dorsum and proceeding distally and plantarward at an angle of 45 degrees. This was then resected at a width of 5–15 mm.

The metatarsal head subsequently was freed from its plantar aspect, and the dislocated base of the proximal phalanx was corrected. The osteotomized bones were then transfixed longitudinally by Kirschner wires from the distal phalanx to the metatarsal base.

A 53-year-old RA patient with forefoot deformities is shown prior to surgery.

Lateral toe reconstruction was performed by means of a metatarsal oblique osteotomy. Photos courtesy Dr. Takeshi Mitsuka

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

VIENNA — Cigarette smoking confers a clear and significant risk of worse clinical outcomes in patients with rheumatoid arthritis and adds to the overall health care burden because of greater therapeutic requirements—including the need for expensive biologic drugs.

Studies have documented an association between smoking and rheumatoid arthritis (RA), but the linkage with specific clinical manifestations has remained unclear. Data from the Consortium of Rheumatology Researchers of North America (CORRONA) now have confirmed that smokers have increased tender and swollen joint counts compared with nonsmokers, as well as an elevated incidence of subcutaneous nodules, Lori A. Lavalle, M.D., said at the annual European congress of rheumatology.

The CORRONA database includes 8,228 patients, drawn from 63 sites across the United States. These patients have been followed since October 2001, with data collection being done approximately every 5 months. A total of 3,266 reported ever having smoked and 1,082 are current smokers, said Dr. Lavalle, who was affiliated with the Albany (N.Y.) Medical College at the time of the presentation.

Among patients who reported ever having smoked, mean tender and swollen joint counts were 4.08 and 4.60, respectively, compared with 3.59 and 4.22 among nonsmokers. This difference was statistically significant, she said.

Other variables—including rheumatoid factor (RF) positivity (76% smokers vs. 69% nonsmokers) and health assessment questionnaire (HAQ) scores (0.53 smokers vs. 0.48 nonsmokers)—also were worse among patients who had ever smoked.

When previous smokers were compared with those who had never smoked, significant differences were seen in HAQ scores, although not in other variables.

The analysis also revealed that a greater percentage of smokers (43%) than nonsmokers (41%) were on biologic agents. In addition, 32% of smokers and 24% of nonsmokers had subcutaneous nodules.

A second study presented in a poster session further highlighted the increased requirement for drug therapy among RA patients who smoke, and particularly among those who are RF positive. This study included 856 patients recruited from 60 German rheumatology clinics, 198 (23.1%) of whom were smokers.

By 6 months, the proportion of patients requiring disease-modifying antirheumatic drugs (DMARDs) was greater among RF-positive smokers than among RF-positive nonsmokers, Gisela Westhoff reported at the meeting, which was sponsored by the European League Against Rheumatism.

This difference increased throughout the 3-year course of the study, and similar differences were seen among RF-negative smokers and nonsmokers. (See table.)

With regard to drug therapy, RF-positive smokers had taken 2.1 different DMARDs by the end of the 3-year study, whereas RF-positive nonsmokers had taken only 1.7, said Ms. Westhoff of the German Rheumatism Research Center, Berlin.

Significantly more smokers were classified as “problematic cases” by their physicians because of inadequate response to treatment, she said.

This ongoing inception cohort study is being funded by the German Federal Minister of Research through the Competence Network Rheumatology.

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

BOSTON — Findings from a recent study provide preliminary evidence that toll-like receptors may play a key role in the response of spondyloarthropathy to treatment with tumor necrosis factor-blocking agents.

Belgian researchers Leen De Rycke, M.D., and colleagues from Ghent (Belgium) University Hospital found increased expression of toll-like receptor (TLR) 2 and TLR4 in the synovium and peripheral blood monocytes of patients with spondyloarthropathy (SpA). Anti-TNF-α drugs successfully suppressed both TLRs, according to their findings, which were presented as a poster at the annual meeting of the Federation of Clinical Immunology Societies.

Dr. De Rycke and colleagues enrolled a small cohort of patients with SpA and rheumatoid arthritis (RA) prior to receiving treatment with TNF-α inhibitors. At baseline and during the 12-week course of therapy, they analyzed synovial biopsies from 18 patients and flow cytometry of peripheral blood monocytes from 38 patients and 9 healthy controls. Findings prior to treatment demonstrated that despite increased expression of both TLRs in RA patients, expression of TLR2 and TLR4 was significantly higher in patients with SpA.

After treatment, there was a “profound effect” of infliximab on monocyte TLR4 expression among SpA patients, and to a lesser extent the same was true in RA patients. In addition, monocyte TLR expression in SpA was below the normal level of healthy controls and TNF-α production was impaired.

Both infliximab and etanercept downregulated synovial TLR expression, “suggesting a class effect of TNF-α blockers,” the investigators wrote. No effects of treatment on symptoms or other clinical findings were reported.

The findings “emphasize a central role for innate immune-mediated inflammation in SpA and provide an additional clue for the efficacy … of TNF-α blockade,” the authors concluded.

The TNF-α blockade may be capable of deterring an exaggerated TLR response. “Spondyloarthropathy inflammation is characterized by increased TLR2 and TLR4 expression, which [is] sharply reduced by TNF-α blockade,” noted Dr. De Rycke and associates. “The strongly reduced TLR surface expression may lead to a decrease in the local and systemic proinflammatory response to autoimmune triggers or microbial agents.”

TLRs play an important part in the innate immune system. While T and B lymphocytes are still preparing an adaptive immune response that takes days to formulate, TLRs are activated within minutes to hours after threatening molecular patterns are detected (J. Pediatr. 2004;144:421–9).

The target of a particular TLR is narrow. TLR4, for example, recognizes organisms that cause gram-negative bacillary septic shock, tuberculosis, and respiratory syncytial virus. Its companion TLR2 goes after gram-positive organisms responsible for other conditions, such as leprosy, Chagas' disease, fungal sepsis, measles, and periodontal disease. Though a TLR's focus is narrow, its powers are broad. For example, in the inflammatory cascade it launches, TLR4 enlists heavyweight genes such as TNF-α, interleukin-1, IL-6, and IL-8.

But problems occur when this finely tuned mechanism goes awry. Emerging evidence suggests that mutations in the TLR genes are associated with increased risk for severe infections and certain diseases.

Faulty TLR4, for example, appears to increase the risk of septic shock (Nat. Genet. 2000;25:187–91). Individuals with mutations in TLR2 produce less TNF-α in response to several microbial infections, leading to outcomes that are sometimes lethal.

Previous work by Dr. Rycke and associates suggested that TLR2 and TLR4 might play a prominent role in SpA synovitis, and differentiate SpA from rheumatoid arthritis (Arthritis Res. Ther. 2005;7:R35969).

CHICAGO — Assessing CD4 T cells at week 4 during the treatment of psoriasis with alefacept can reduce the need for further lymphocyte monitoring in some patients, Jennifer Cather, M.D., reported at the International Psoriasis Symposium sponsored by the Skin Disease Education Foundation.

The strategy could also lower costs and make alefacept therapy more convenient, she added.

Weekly CD4 counts are required by the alefacept (Amevive) package insert throughout the 12-week treatment regimen and are done as standard of care.

Dr. Cather suggested that the counts at week 4 can predict with a high degree of accuracy what the counts for weeks 5–12 will be.

If the count is more than 600 cells/μL at week 4, there is less than a 0.1% chance of having a subsequent CD4 count fall below 250 cells/μL, Dr. Cather said.

Therefore, she explained, weekly monitoring during the remaining treatment may be unnecessary in these patients.

Monitoring should be performed monthly for patients with a count between 400 cells/μL and 600 cells/μL, and every 2 weeks if the count is less than 400 cells/μL at week 4.

If a patient's CD4 count is less than 250 cells/μL at any time during alefacept treatment, the drug is usually withheld and testing should be done weekly until the count is 250 cells/μL or greater.

The recommendations are from a proposed monitoring algorithm based on a mathematical model and later confirmed at Baylor University Medical Center at Dallas, where Dr. Cather is codirector of the cutaneous lymphoma and graft vs. host disease clinic.

Biogen Idec, which makes alefacept, revised its package insert for the biologic last year after concerns were raised about serious liver injury in two patients. It is important to monitor for liver enzyme elevations in patients with psoriasis and psoriatic arthritis, said Dr. Cather, who has received funding support from Biogen Idec.

“I think that the hepatotoxicity that we see with a lot of these biologics is because the patient's liver is different,” she said. “Perhaps the increased hepatotoxicity is a result of increased body mass index and steatohepatitis.”

Ongoing trials are evaluating whether longer treatment with alefacept is needed to improve its efficacy, suggesting that long-term monitoring will remain important for physicians and patients.

Early data suggest that the addition of four doses to the 12-week treatment regimen increased response rates in patients with psoriasis, and that multiple courses may improve clinical responses in psoriasis patients who fail to show a strong initial response, she said.

“In addition, there are some data that show that their duration of remission in between each course improves with multiple courses,” said Dr. Cather.

In 197 patients with psoriasis who received 264 courses of alefacept at Baylor University independent of clinical trials, CD4 counts did not fall below 400 cells/μL in any of the patients, she said.

A total of 109 (41%) of treatments were 12-week courses of alefacept in combination with other therapies, including methotrexate, cyclosporine, hydroxyurea, ultraviolet B light, and acitretin. A total of 83 (32%) were standard 12-week alefacept monotherapy courses; 63 (24%) were extended courses of alefacept for 12 or more weeks either as monotherapy or in combination with other agents; and 8 (3%) were double-dose or alternative-dosing regimens.

The most common adverse events were fatigue, joint pain, aches, and chills.

There were five cases of infection, four malignancies including three skin cancers and one case of lung cancer, and no cases of liver or kidney toxicity.

Dr. Cather noted that in a recent case report of alefacept in two patients with hepatitis C infection and psoriasis, decreases in CD4 and CD8 counts were transient, and were not associated with either an increase in hepatitis viral loads or exacerbation of infection (Br. J. Dermatol. 2005;152:1048–50).

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

CHICAGO — Assessing CD4 T cells at week 4 during the treatment of psoriasis with alefacept can reduce the need for further lymphocyte monitoring in some patients, Jennifer Cather, M.D., reported at the International Psoriasis Symposium sponsored by the Skin Disease Education Foundation.

The strategy could also lower costs and make alefacept therapy more convenient, she added.

Weekly CD4 counts are required by the alefacept (Amevive) package insert throughout the 12-week treatment regimen and are done as standard of care.

Dr. Cather suggested that the counts at week 4 can predict with a high degree of accuracy what the counts for weeks 5–12 will be.

If the count is more than 600 cells/μL at week 4, there is less than a 0.1% chance of having a subsequent CD4 count fall below 250 cells/μL, Dr. Cather said.

Therefore, she explained, weekly monitoring during the remaining treatment may be unnecessary in these patients.

Monitoring should be performed monthly for patients with a count between 400 cells/μL and 600 cells/μL, and every 2 weeks if the count is less than 400 cells/μL at week 4.

If a patient's CD4 count is less than 250 cells/μL at any time during alefacept treatment, the drug is usually withheld and testing should be done weekly until the count is 250 cells/μL or greater.

The recommendations are from a proposed monitoring algorithm based on a mathematical model and later confirmed at Baylor University Medical Center at Dallas, where Dr. Cather is codirector of the cutaneous lymphoma and graft vs. host disease clinic.

Biogen Idec, which makes alefacept, revised its package insert for the biologic last year after concerns were raised about serious liver injury in two patients. It is important to monitor for liver enzyme elevations in patients with psoriasis and psoriatic arthritis, said Dr. Cather, who has received funding support from Biogen Idec.

“I think that the hepatotoxicity that we see with a lot of these biologics is because the patient's liver is different,” she said. “Perhaps the increased hepatotoxicity is a result of increased body mass index and steatohepatitis.”

Ongoing trials are evaluating whether longer treatment with alefacept is needed to improve its efficacy, suggesting that long-term monitoring will remain important for physicians and patients.

Early data suggest that the addition of four doses to the 12-week treatment regimen increased response rates in patients with psoriasis, and that multiple courses may improve clinical responses in psoriasis patients who fail to show a strong initial response, she said.

“In addition, there are some data that show that their duration of remission in between each course improves with multiple courses,” said Dr. Cather.

In 197 patients with psoriasis who received 264 courses of alefacept at Baylor University independent of clinical trials, CD4 counts did not fall below 400 cells/μL in any of the patients, she said.

A total of 109 (41%) of treatments were 12-week courses of alefacept in combination with other therapies, including methotrexate, cyclosporine, hydroxyurea, ultraviolet B light, and acitretin. A total of 83 (32%) were standard 12-week alefacept monotherapy courses; 63 (24%) were extended courses of alefacept for 12 or more weeks either as monotherapy or in combination with other agents; and 8 (3%) were double-dose or alternative-dosing regimens.

The most common adverse events were fatigue, joint pain, aches, and chills.

There were five cases of infection, four malignancies including three skin cancers and one case of lung cancer, and no cases of liver or kidney toxicity.

Dr. Cather noted that in a recent case report of alefacept in two patients with hepatitis C infection and psoriasis, decreases in CD4 and CD8 counts were transient, and were not associated with either an increase in hepatitis viral loads or exacerbation of infection (Br. J. Dermatol. 2005;152:1048–50).

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

CHICAGO — Assessing CD4 T cells at week 4 during the treatment of psoriasis with alefacept can reduce the need for further lymphocyte monitoring in some patients, Jennifer Cather, M.D., reported at the International Psoriasis Symposium sponsored by the Skin Disease Education Foundation.

The strategy could also lower costs and make alefacept therapy more convenient, she added.

Weekly CD4 counts are required by the alefacept (Amevive) package insert throughout the 12-week treatment regimen and are done as standard of care.

Dr. Cather suggested that the counts at week 4 can predict with a high degree of accuracy what the counts for weeks 5–12 will be.

If the count is more than 600 cells/μL at week 4, there is less than a 0.1% chance of having a subsequent CD4 count fall below 250 cells/μL, Dr. Cather said.

Therefore, she explained, weekly monitoring during the remaining treatment may be unnecessary in these patients.

Monitoring should be performed monthly for patients with a count between 400 cells/μL and 600 cells/μL, and every 2 weeks if the count is less than 400 cells/μL at week 4.

If a patient's CD4 count is less than 250 cells/μL at any time during alefacept treatment, the drug is usually withheld and testing should be done weekly until the count is 250 cells/μL or greater.

The recommendations are from a proposed monitoring algorithm based on a mathematical model and later confirmed at Baylor University Medical Center at Dallas, where Dr. Cather is codirector of the cutaneous lymphoma and graft vs. host disease clinic.

Biogen Idec, which makes alefacept, revised its package insert for the biologic last year after concerns were raised about serious liver injury in two patients. It is important to monitor for liver enzyme elevations in patients with psoriasis and psoriatic arthritis, said Dr. Cather, who has received funding support from Biogen Idec.

“I think that the hepatotoxicity that we see with a lot of these biologics is because the patient's liver is different,” she said. “Perhaps the increased hepatotoxicity is a result of increased body mass index and steatohepatitis.”

Ongoing trials are evaluating whether longer treatment with alefacept is needed to improve its efficacy, suggesting that long-term monitoring will remain important for physicians and patients.

Early data suggest that the addition of four doses to the 12-week treatment regimen increased response rates in patients with psoriasis, and that multiple courses may improve clinical responses in psoriasis patients who fail to show a strong initial response, she said.

“In addition, there are some data that show that their duration of remission in between each course improves with multiple courses,” said Dr. Cather.

In 197 patients with psoriasis who received 264 courses of alefacept at Baylor University independent of clinical trials, CD4 counts did not fall below 400 cells/μL in any of the patients, she said.

A total of 109 (41%) of treatments were 12-week courses of alefacept in combination with other therapies, including methotrexate, cyclosporine, hydroxyurea, ultraviolet B light, and acitretin. A total of 83 (32%) were standard 12-week alefacept monotherapy courses; 63 (24%) were extended courses of alefacept for 12 or more weeks either as monotherapy or in combination with other agents; and 8 (3%) were double-dose or alternative-dosing regimens.

The most common adverse events were fatigue, joint pain, aches, and chills.

There were five cases of infection, four malignancies including three skin cancers and one case of lung cancer, and no cases of liver or kidney toxicity.

Dr. Cather noted that in a recent case report of alefacept in two patients with hepatitis C infection and psoriasis, decreases in CD4 and CD8 counts were transient, and were not associated with either an increase in hepatitis viral loads or exacerbation of infection (Br. J. Dermatol. 2005;152:1048–50).

The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

NEW ORLEANS — Etanercept appears to be a safe therapeutic option in psoriasis patients with concurrent hepatitis C, according to the results of a retrospective case series.

“Not only does it appear to be safe, it might even be beneficial for the patient's underlying hepatitis,” Erin J. Allen, M.D., proposed during a poster presentation at the annual meeting of the American Academy of Dermatology.

Hepatitis viral loads decreased in two of the five patients receiving etanercept (Enbrel) 25 mg twice weekly for up to 14 months. Three patients had decreased liver transaminases.

Of the two patients with elevated transaminases, one discontinued interferon prematurely just before starting etanercept, so the worsening transaminases were not unexpected, said Dr. Allen, a dermatologist at St. Louis University. In the other patient, a significant elevation was noted only in alanine transaminase and not in the transaminase levels.

All patients showed marked improvement of their psoriasis, with three of the five patients becoming “clear” or “almost clear” on the physicians' global assessment.

Two patients experienced a flare when started on interferon, but still tolerated the interferon, and psoriasis remained less than 10% of body surface area.

Etanercept, an anti-tumor necrosis factor (TNF) therapy, was a rational choice for these patients because TNF is elevated in both hepatitis C and psoriasis, said Dr. Allen, who has participated in etanercept trials, but didn't receive funding for the series.

Although the exact mechanism is not known, etanercept neutralizes the proinflammatory effects of TNF by preventing soluble TNF-α and TNF-β from binding to their receptors.

The case series joins a very limited amount of literature evaluating the use of etanercept (Enbrel) in patients with rheumatoid arthritis (RA) or psoriasis and concurrent hepatitis C (HCV).

According to the literature, treatment with etanercept did not worsen the underlying hepatitis in three psoriasis patients (J. Am. Acad. Dermatol. 2004;51:580–4) and improved the serum transaminases and viral loads in some patients with RA and HCV (J. Dermatolog. Treat. 2003;14:229–32).

Although etanercept was generally well tolerated, Dr. Allen recommended that all psoriasis patients with concurrent hepatitis C be closely monitored in conjunction with a hepatologist until more data are available.

NEW ORLEANS — Etanercept appears to be a safe therapeutic option in psoriasis patients with concurrent hepatitis C, according to the results of a retrospective case series.

“Not only does it appear to be safe, it might even be beneficial for the patient's underlying hepatitis,” Erin J. Allen, M.D., proposed during a poster presentation at the annual meeting of the American Academy of Dermatology.

Hepatitis viral loads decreased in two of the five patients receiving etanercept (Enbrel) 25 mg twice weekly for up to 14 months. Three patients had decreased liver transaminases.

Of the two patients with elevated transaminases, one discontinued interferon prematurely just before starting etanercept, so the worsening transaminases were not unexpected, said Dr. Allen, a dermatologist at St. Louis University. In the other patient, a significant elevation was noted only in alanine transaminase and not in the transaminase levels.

All patients showed marked improvement of their psoriasis, with three of the five patients becoming “clear” or “almost clear” on the physicians' global assessment.

Two patients experienced a flare when started on interferon, but still tolerated the interferon, and psoriasis remained less than 10% of body surface area.

Etanercept, an anti-tumor necrosis factor (TNF) therapy, was a rational choice for these patients because TNF is elevated in both hepatitis C and psoriasis, said Dr. Allen, who has participated in etanercept trials, but didn't receive funding for the series.

Although the exact mechanism is not known, etanercept neutralizes the proinflammatory effects of TNF by preventing soluble TNF-α and TNF-β from binding to their receptors.

The case series joins a very limited amount of literature evaluating the use of etanercept (Enbrel) in patients with rheumatoid arthritis (RA) or psoriasis and concurrent hepatitis C (HCV).

According to the literature, treatment with etanercept did not worsen the underlying hepatitis in three psoriasis patients (J. Am. Acad. Dermatol. 2004;51:580–4) and improved the serum transaminases and viral loads in some patients with RA and HCV (J. Dermatolog. Treat. 2003;14:229–32).

Although etanercept was generally well tolerated, Dr. Allen recommended that all psoriasis patients with concurrent hepatitis C be closely monitored in conjunction with a hepatologist until more data are available.

NEW ORLEANS — Etanercept appears to be a safe therapeutic option in psoriasis patients with concurrent hepatitis C, according to the results of a retrospective case series.

“Not only does it appear to be safe, it might even be beneficial for the patient's underlying hepatitis,” Erin J. Allen, M.D., proposed during a poster presentation at the annual meeting of the American Academy of Dermatology.

Hepatitis viral loads decreased in two of the five patients receiving etanercept (Enbrel) 25 mg twice weekly for up to 14 months. Three patients had decreased liver transaminases.

Of the two patients with elevated transaminases, one discontinued interferon prematurely just before starting etanercept, so the worsening transaminases were not unexpected, said Dr. Allen, a dermatologist at St. Louis University. In the other patient, a significant elevation was noted only in alanine transaminase and not in the transaminase levels.

All patients showed marked improvement of their psoriasis, with three of the five patients becoming “clear” or “almost clear” on the physicians' global assessment.

Two patients experienced a flare when started on interferon, but still tolerated the interferon, and psoriasis remained less than 10% of body surface area.

Etanercept, an anti-tumor necrosis factor (TNF) therapy, was a rational choice for these patients because TNF is elevated in both hepatitis C and psoriasis, said Dr. Allen, who has participated in etanercept trials, but didn't receive funding for the series.

Although the exact mechanism is not known, etanercept neutralizes the proinflammatory effects of TNF by preventing soluble TNF-α and TNF-β from binding to their receptors.

The case series joins a very limited amount of literature evaluating the use of etanercept (Enbrel) in patients with rheumatoid arthritis (RA) or psoriasis and concurrent hepatitis C (HCV).

According to the literature, treatment with etanercept did not worsen the underlying hepatitis in three psoriasis patients (J. Am. Acad. Dermatol. 2004;51:580–4) and improved the serum transaminases and viral loads in some patients with RA and HCV (J. Dermatolog. Treat. 2003;14:229–32).

Although etanercept was generally well tolerated, Dr. Allen recommended that all psoriasis patients with concurrent hepatitis C be closely monitored in conjunction with a hepatologist until more data are available.