Rheumatoid Arthritis

PARIS — When it comes to psoriatic arthritis, don't forget the feet.

The foot is a neglected area of the body in patients with psoriatic arthritis. The burden of foot pain and deformity is high and the level of foot care provision is low, Deborah E. Turner, Ph.D., reported at the annual European Congress of Rheumatology.

A big part of the reason the feet of psoriatic arthritis patients are underassessed clinically is that the disease activity measures widely used in both clinical practice and research ignore the foot, according to Dr. Turner of Glasgow (Scotland) Caledonian University.

She reported on an unselected series of 88 consecutive psoriatic arthritis patients at Glasgow Royal Infirmary who underwent a clinical foot examination by a podiatrist. Two-thirds of the patients reported chronic foot pain; in most cases, the medical team was unaware of the problem because nobody had ever asked.

“Patients generally don't tend to offer this information. They'll mention other areas—the hand, the spine—but not the feet,” Dr. Turner observed.

On clinical examination, 30% of the cohort had plantar fasciitis and 24% had Achilles tendonitis. These are probably marked underestimates of the true prevalence of pathology at these sites, as ultrasound studies have shown that roughly three-quarters of psoriatic arthritis patients are affected.

A novel finding reported for the first time in this study was that 40% of the psoriatic arthritis patients had inflammatory involvement of the posterior tibial tendon.

“While it's not a classical enthesis, it is categorized as a functional enthesis because it has an element of fibrocartilage under the tendon at the point at which it goes over the malleolus,” she continued.

Joint tenderness was detected in one or more of the metatarsophalangeal joints of nearly half of subjects, while the interphalangeal joints were affected in one-third.

A striking finding in the study was the very high prevalence of flat feet in the patients with significant foot pain. Why should psoriatic arthritis be strongly associated with a low arch profile? The working hypothesis is that a combination of inflammation of tendons and in the joints around the ankle and rear foot leads to weakened foot ligaments, which then stretch under the stress of weight bearing, resulting in flattening of the arch. This theory requires confirmation in planned follow-up imaging studies utilizing MRI and ultrasound, Dr. Turner said.

She added that foot problems are often one of the earliest features of psoriatic arthritis. A common scenario in young patients participating in sports is that months before they receive the diagnosis of psoriatic arthritis, they develop Achilles tendonitis and/or plantar fasciitis, which are misinterpreted solely as chronic overuse athletic injuries.

Mean scores on the Leeds Foot Impact Scale impairment and activity limitation subscales in the Glasgow psoriatic arthritis cohort were similar to those typically associated with rheumatoid arthritis.

“A lot of attention is given to foot problems in rheumatoid arthritis, but we found the overall burden of foot problems in terms of how much they contribute to the patients' disability was as high for patients with psoriatic arthritis as for those with rheumatoid arthritis,” Dr. Turner said in an interview.

Nevertheless, only one-quarter of study participants had received conservative foot care.

The standard podiatric treatment for painful flat foot deformities is the use of a rigid arch support. As part of Dr. Turner's ongoing research project funded by the Arthritis Research Campaign, she plans to see whether correcting the abnormal foot mechanics in psoriatic arthritis patients improves their inflamed lower extremity joints and tendons.

She stressed that detecting foot problems in psoriatic arthritis patients is a straightforward matter for physicians regardless of whether they are rheumatologists, dermatologists, or primary care physicians. All they have to do is look for them.

“It's a matter of assessing the key structures for tenderness and swelling, as is part of the routine assessment procedures they do elsewhere on the body. If they note that the patient has a low arch profile and the heel is not vertical and is collapsed, they can send the patient off to a podiatrist for treatment,” Dr. Turner said.

PARIS — When it comes to psoriatic arthritis, don't forget the feet.

The foot is a neglected area of the body in patients with psoriatic arthritis. The burden of foot pain and deformity is high and the level of foot care provision is low, Deborah E. Turner, Ph.D., reported at the annual European Congress of Rheumatology.

A big part of the reason the feet of psoriatic arthritis patients are underassessed clinically is that the disease activity measures widely used in both clinical practice and research ignore the foot, according to Dr. Turner of Glasgow (Scotland) Caledonian University.

She reported on an unselected series of 88 consecutive psoriatic arthritis patients at Glasgow Royal Infirmary who underwent a clinical foot examination by a podiatrist. Two-thirds of the patients reported chronic foot pain; in most cases, the medical team was unaware of the problem because nobody had ever asked.

“Patients generally don't tend to offer this information. They'll mention other areas—the hand, the spine—but not the feet,” Dr. Turner observed.

On clinical examination, 30% of the cohort had plantar fasciitis and 24% had Achilles tendonitis. These are probably marked underestimates of the true prevalence of pathology at these sites, as ultrasound studies have shown that roughly three-quarters of psoriatic arthritis patients are affected.

A novel finding reported for the first time in this study was that 40% of the psoriatic arthritis patients had inflammatory involvement of the posterior tibial tendon.

“While it's not a classical enthesis, it is categorized as a functional enthesis because it has an element of fibrocartilage under the tendon at the point at which it goes over the malleolus,” she continued.

Joint tenderness was detected in one or more of the metatarsophalangeal joints of nearly half of subjects, while the interphalangeal joints were affected in one-third.

A striking finding in the study was the very high prevalence of flat feet in the patients with significant foot pain. Why should psoriatic arthritis be strongly associated with a low arch profile? The working hypothesis is that a combination of inflammation of tendons and in the joints around the ankle and rear foot leads to weakened foot ligaments, which then stretch under the stress of weight bearing, resulting in flattening of the arch. This theory requires confirmation in planned follow-up imaging studies utilizing MRI and ultrasound, Dr. Turner said.

She added that foot problems are often one of the earliest features of psoriatic arthritis. A common scenario in young patients participating in sports is that months before they receive the diagnosis of psoriatic arthritis, they develop Achilles tendonitis and/or plantar fasciitis, which are misinterpreted solely as chronic overuse athletic injuries.

Mean scores on the Leeds Foot Impact Scale impairment and activity limitation subscales in the Glasgow psoriatic arthritis cohort were similar to those typically associated with rheumatoid arthritis.

“A lot of attention is given to foot problems in rheumatoid arthritis, but we found the overall burden of foot problems in terms of how much they contribute to the patients' disability was as high for patients with psoriatic arthritis as for those with rheumatoid arthritis,” Dr. Turner said in an interview.

Nevertheless, only one-quarter of study participants had received conservative foot care.

The standard podiatric treatment for painful flat foot deformities is the use of a rigid arch support. As part of Dr. Turner's ongoing research project funded by the Arthritis Research Campaign, she plans to see whether correcting the abnormal foot mechanics in psoriatic arthritis patients improves their inflamed lower extremity joints and tendons.

She stressed that detecting foot problems in psoriatic arthritis patients is a straightforward matter for physicians regardless of whether they are rheumatologists, dermatologists, or primary care physicians. All they have to do is look for them.

“It's a matter of assessing the key structures for tenderness and swelling, as is part of the routine assessment procedures they do elsewhere on the body. If they note that the patient has a low arch profile and the heel is not vertical and is collapsed, they can send the patient off to a podiatrist for treatment,” Dr. Turner said.

PARIS — When it comes to psoriatic arthritis, don't forget the feet.

The foot is a neglected area of the body in patients with psoriatic arthritis. The burden of foot pain and deformity is high and the level of foot care provision is low, Deborah E. Turner, Ph.D., reported at the annual European Congress of Rheumatology.

A big part of the reason the feet of psoriatic arthritis patients are underassessed clinically is that the disease activity measures widely used in both clinical practice and research ignore the foot, according to Dr. Turner of Glasgow (Scotland) Caledonian University.

She reported on an unselected series of 88 consecutive psoriatic arthritis patients at Glasgow Royal Infirmary who underwent a clinical foot examination by a podiatrist. Two-thirds of the patients reported chronic foot pain; in most cases, the medical team was unaware of the problem because nobody had ever asked.

“Patients generally don't tend to offer this information. They'll mention other areas—the hand, the spine—but not the feet,” Dr. Turner observed.

On clinical examination, 30% of the cohort had plantar fasciitis and 24% had Achilles tendonitis. These are probably marked underestimates of the true prevalence of pathology at these sites, as ultrasound studies have shown that roughly three-quarters of psoriatic arthritis patients are affected.

A novel finding reported for the first time in this study was that 40% of the psoriatic arthritis patients had inflammatory involvement of the posterior tibial tendon.

“While it's not a classical enthesis, it is categorized as a functional enthesis because it has an element of fibrocartilage under the tendon at the point at which it goes over the malleolus,” she continued.

Joint tenderness was detected in one or more of the metatarsophalangeal joints of nearly half of subjects, while the interphalangeal joints were affected in one-third.

A striking finding in the study was the very high prevalence of flat feet in the patients with significant foot pain. Why should psoriatic arthritis be strongly associated with a low arch profile? The working hypothesis is that a combination of inflammation of tendons and in the joints around the ankle and rear foot leads to weakened foot ligaments, which then stretch under the stress of weight bearing, resulting in flattening of the arch. This theory requires confirmation in planned follow-up imaging studies utilizing MRI and ultrasound, Dr. Turner said.

She added that foot problems are often one of the earliest features of psoriatic arthritis. A common scenario in young patients participating in sports is that months before they receive the diagnosis of psoriatic arthritis, they develop Achilles tendonitis and/or plantar fasciitis, which are misinterpreted solely as chronic overuse athletic injuries.

Mean scores on the Leeds Foot Impact Scale impairment and activity limitation subscales in the Glasgow psoriatic arthritis cohort were similar to those typically associated with rheumatoid arthritis.

“A lot of attention is given to foot problems in rheumatoid arthritis, but we found the overall burden of foot problems in terms of how much they contribute to the patients' disability was as high for patients with psoriatic arthritis as for those with rheumatoid arthritis,” Dr. Turner said in an interview.

Nevertheless, only one-quarter of study participants had received conservative foot care.

The standard podiatric treatment for painful flat foot deformities is the use of a rigid arch support. As part of Dr. Turner's ongoing research project funded by the Arthritis Research Campaign, she plans to see whether correcting the abnormal foot mechanics in psoriatic arthritis patients improves their inflamed lower extremity joints and tendons.

She stressed that detecting foot problems in psoriatic arthritis patients is a straightforward matter for physicians regardless of whether they are rheumatologists, dermatologists, or primary care physicians. All they have to do is look for them.

“It's a matter of assessing the key structures for tenderness and swelling, as is part of the routine assessment procedures they do elsewhere on the body. If they note that the patient has a low arch profile and the heel is not vertical and is collapsed, they can send the patient off to a podiatrist for treatment,” Dr. Turner said.

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

PARIS — The overwhelming majority of osteoarthritis patients who will respond favorably to a given cyclooxygenase-2 selective NSAID will do so within the first 2 weeks, a pooled analysis of two placebo-controlled clinical trials has shown.

Thus, the 2-week mark is a reasonable time in which to consider whether to switch a patient to a different NSAID, Dr. Steven S. Smugar said at the annual European Congress of Rheumatology.

However, a case also can be made for using a more conservative decision point at 4 weeks. That's because 28% of nonresponders after 2 weeks became responders by week 4 in this post hoc pooled analysis. But the absolute number of patients who fell into this delayed-responder subgroup was small, added Dr. Smugar of Merck & Co., West Point, Pa.

He reported on 1,207 patients with knee or hip osteoarthritis who were randomized to 12 weeks of once-daily etoricoxib (Arcoxia, not available in United States) at 30 mg, celecoxib (Celebrex) at 200 mg, or placebo in two identical double-blind clinical trials sponsored by Merck.

After 12 weeks, 66% of patients in the etoricoxib group, 64% in the celecoxib group, and 43% on placebo had a favorable response as defined primarily by at least a 50% improvement in pain or function and an absolute change of 20 mm or more on a 100-mm visual analog scale.

Eighty-four percent of responders at week 2 remained responders at week 12. The durability of response was good, demonstrated by the fact that, among responders, 74% were consistent responders at all four of the study assessment points at 2, 4, 8, and 12 weeks, according to Dr. Smugar.

Of 360 nonresponders at week 2, 60% remained nonresponders at week 12.

PARIS — The overwhelming majority of osteoarthritis patients who will respond favorably to a given cyclooxygenase-2 selective NSAID will do so within the first 2 weeks, a pooled analysis of two placebo-controlled clinical trials has shown.

Thus, the 2-week mark is a reasonable time in which to consider whether to switch a patient to a different NSAID, Dr. Steven S. Smugar said at the annual European Congress of Rheumatology.

However, a case also can be made for using a more conservative decision point at 4 weeks. That's because 28% of nonresponders after 2 weeks became responders by week 4 in this post hoc pooled analysis. But the absolute number of patients who fell into this delayed-responder subgroup was small, added Dr. Smugar of Merck & Co., West Point, Pa.

He reported on 1,207 patients with knee or hip osteoarthritis who were randomized to 12 weeks of once-daily etoricoxib (Arcoxia, not available in United States) at 30 mg, celecoxib (Celebrex) at 200 mg, or placebo in two identical double-blind clinical trials sponsored by Merck.

After 12 weeks, 66% of patients in the etoricoxib group, 64% in the celecoxib group, and 43% on placebo had a favorable response as defined primarily by at least a 50% improvement in pain or function and an absolute change of 20 mm or more on a 100-mm visual analog scale.

Eighty-four percent of responders at week 2 remained responders at week 12. The durability of response was good, demonstrated by the fact that, among responders, 74% were consistent responders at all four of the study assessment points at 2, 4, 8, and 12 weeks, according to Dr. Smugar.

Of 360 nonresponders at week 2, 60% remained nonresponders at week 12.

PARIS — The overwhelming majority of osteoarthritis patients who will respond favorably to a given cyclooxygenase-2 selective NSAID will do so within the first 2 weeks, a pooled analysis of two placebo-controlled clinical trials has shown.

Thus, the 2-week mark is a reasonable time in which to consider whether to switch a patient to a different NSAID, Dr. Steven S. Smugar said at the annual European Congress of Rheumatology.

However, a case also can be made for using a more conservative decision point at 4 weeks. That's because 28% of nonresponders after 2 weeks became responders by week 4 in this post hoc pooled analysis. But the absolute number of patients who fell into this delayed-responder subgroup was small, added Dr. Smugar of Merck & Co., West Point, Pa.

He reported on 1,207 patients with knee or hip osteoarthritis who were randomized to 12 weeks of once-daily etoricoxib (Arcoxia, not available in United States) at 30 mg, celecoxib (Celebrex) at 200 mg, or placebo in two identical double-blind clinical trials sponsored by Merck.

After 12 weeks, 66% of patients in the etoricoxib group, 64% in the celecoxib group, and 43% on placebo had a favorable response as defined primarily by at least a 50% improvement in pain or function and an absolute change of 20 mm or more on a 100-mm visual analog scale.

Eighty-four percent of responders at week 2 remained responders at week 12. The durability of response was good, demonstrated by the fact that, among responders, 74% were consistent responders at all four of the study assessment points at 2, 4, 8, and 12 weeks, according to Dr. Smugar.

Of 360 nonresponders at week 2, 60% remained nonresponders at week 12.

OLYMPIC VALLEY, CALIF. — A new minimally invasive procedure dramatically reduced pain and disability for a small group of patients with lumbar spinal stenosis. No complications or adverse events were reported, and patients were discharged the same day or the next day.

The procedure is performed using the MILD (minimally invasive lumbar decompression) device that allows practitioners to perform a lumbar decompression to remove bone to access the area of stenosis under fluoroscopic guidance, and then widen and decompress the canal by thinning or sculpting the bone and enlarged ligaments that compress the nerve roots. Low back pain, leg fatigue and pain, and physical impairments are attributed to this compression, according to Dr. Joshua A. Hirsch.

“I view the MILD procedure as part of a broadening array of treatments that minimally invasive spine specialists can offer patients with lumbar spinal stenosis,” said Dr. Hirsch, director of interventional neuroradiology/endovascular neurosurgery and chief of minimally invasive spine surgery at Massachusetts General Hospital, Boston.

As of July 2008, 42 patients with severe spinal stenosis underwent the MILD procedure. Ten patients were followed under an institutional review board-approved protocol designed to assess improvement in pain using a Visual Analog Scale (VAS), and disability using the Oswestry Disability Index (ODI). Preoperatively, these patients had ODI scores of 60%–80%, indicating that they were crippled by their condition, and VAS pain scores of 6–10.

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline (ODI 0%–20%) and the mean pain score decreased by 90% (VAS scores at 1). All 10 patients had discontinued narcotics use for pain by 6 weeks post op and were discharged from the hospital on the same day or the day following the procedure. “These are phenomenal results,” said Dr. Hirsch, who noted that these initial promising results must be validated by further study.

No complications have been reported from the procedure. Other advantages of the procedure are that it requires only local sedation, allows patients to recover quickly, and offers the possibility of delaying or preventing more invasive surgery. The incisions are smaller than a dime, said Dr. Hirsch, who presented his findings at the annual meeting of the Society of Neurointerventional Surgery and received travel support from the device's manufacturer, Vertos Medical Inc., of San Jose, Calif.

During an interview, Dr. Allan L. Brook, director of interventional neuroradiology at Montefiore Medical Center, New York, said he has used the MILD device in three cases. Montefiore is 1 of 10 sites participating in the Vertos-sponsored MILD Preliminary Patient Evaluation Study, a multicenter, prospective clinical study to assess the clinical application and outcomes of minimally invasive lumbar decompression with the devices in patients who have symptomatic spinal stenosis.

“These patients have had dramatic pain relief. The majority of these patients have exhausted standard medical therapies, as well as numerous other less invasive injections. I believe many patients could benefit from this minimally invasive posterior lumbar decompression,” said Dr. Brook. He noted that there are no other percutaneous procedures that attempt to remove the soft tissue that impinges from behind the nerves; most aim to remove the disk or rely upon open surgical techniques, with their known risks.

Dr. Brooks reported that he has no financial relationship with Vertos Medical.

“Lumbar spinal stenosis is a huge problem which really impacts people's quality of life. Approximately 1.5 million people in the U.S. are diagnosed with it every year—about twice the number of those who have vertebral compression fractures,” said Dr. Hirsch. “The MILD device allows us to provide a minimally invasive alternative to traditional laminectomy/laminotomy.”

In the first step, the bone rongeur is utilized to remove posterior bone.

A bone-removing device accesses ligamentum flavum.

The soft tissue rongeur removes ligament posterior to epidural space. Photos courtesy Dr. Allan L. Brook

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline. DR. HIRSH

OLYMPIC VALLEY, CALIF. — A new minimally invasive procedure dramatically reduced pain and disability for a small group of patients with lumbar spinal stenosis. No complications or adverse events were reported, and patients were discharged the same day or the next day.

The procedure is performed using the MILD (minimally invasive lumbar decompression) device that allows practitioners to perform a lumbar decompression to remove bone to access the area of stenosis under fluoroscopic guidance, and then widen and decompress the canal by thinning or sculpting the bone and enlarged ligaments that compress the nerve roots. Low back pain, leg fatigue and pain, and physical impairments are attributed to this compression, according to Dr. Joshua A. Hirsch.

“I view the MILD procedure as part of a broadening array of treatments that minimally invasive spine specialists can offer patients with lumbar spinal stenosis,” said Dr. Hirsch, director of interventional neuroradiology/endovascular neurosurgery and chief of minimally invasive spine surgery at Massachusetts General Hospital, Boston.

As of July 2008, 42 patients with severe spinal stenosis underwent the MILD procedure. Ten patients were followed under an institutional review board-approved protocol designed to assess improvement in pain using a Visual Analog Scale (VAS), and disability using the Oswestry Disability Index (ODI). Preoperatively, these patients had ODI scores of 60%–80%, indicating that they were crippled by their condition, and VAS pain scores of 6–10.

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline (ODI 0%–20%) and the mean pain score decreased by 90% (VAS scores at 1). All 10 patients had discontinued narcotics use for pain by 6 weeks post op and were discharged from the hospital on the same day or the day following the procedure. “These are phenomenal results,” said Dr. Hirsch, who noted that these initial promising results must be validated by further study.

No complications have been reported from the procedure. Other advantages of the procedure are that it requires only local sedation, allows patients to recover quickly, and offers the possibility of delaying or preventing more invasive surgery. The incisions are smaller than a dime, said Dr. Hirsch, who presented his findings at the annual meeting of the Society of Neurointerventional Surgery and received travel support from the device's manufacturer, Vertos Medical Inc., of San Jose, Calif.

During an interview, Dr. Allan L. Brook, director of interventional neuroradiology at Montefiore Medical Center, New York, said he has used the MILD device in three cases. Montefiore is 1 of 10 sites participating in the Vertos-sponsored MILD Preliminary Patient Evaluation Study, a multicenter, prospective clinical study to assess the clinical application and outcomes of minimally invasive lumbar decompression with the devices in patients who have symptomatic spinal stenosis.

“These patients have had dramatic pain relief. The majority of these patients have exhausted standard medical therapies, as well as numerous other less invasive injections. I believe many patients could benefit from this minimally invasive posterior lumbar decompression,” said Dr. Brook. He noted that there are no other percutaneous procedures that attempt to remove the soft tissue that impinges from behind the nerves; most aim to remove the disk or rely upon open surgical techniques, with their known risks.

Dr. Brooks reported that he has no financial relationship with Vertos Medical.

“Lumbar spinal stenosis is a huge problem which really impacts people's quality of life. Approximately 1.5 million people in the U.S. are diagnosed with it every year—about twice the number of those who have vertebral compression fractures,” said Dr. Hirsch. “The MILD device allows us to provide a minimally invasive alternative to traditional laminectomy/laminotomy.”

In the first step, the bone rongeur is utilized to remove posterior bone.

A bone-removing device accesses ligamentum flavum.

The soft tissue rongeur removes ligament posterior to epidural space. Photos courtesy Dr. Allan L. Brook

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline. DR. HIRSH

OLYMPIC VALLEY, CALIF. — A new minimally invasive procedure dramatically reduced pain and disability for a small group of patients with lumbar spinal stenosis. No complications or adverse events were reported, and patients were discharged the same day or the next day.

The procedure is performed using the MILD (minimally invasive lumbar decompression) device that allows practitioners to perform a lumbar decompression to remove bone to access the area of stenosis under fluoroscopic guidance, and then widen and decompress the canal by thinning or sculpting the bone and enlarged ligaments that compress the nerve roots. Low back pain, leg fatigue and pain, and physical impairments are attributed to this compression, according to Dr. Joshua A. Hirsch.

“I view the MILD procedure as part of a broadening array of treatments that minimally invasive spine specialists can offer patients with lumbar spinal stenosis,” said Dr. Hirsch, director of interventional neuroradiology/endovascular neurosurgery and chief of minimally invasive spine surgery at Massachusetts General Hospital, Boston.

As of July 2008, 42 patients with severe spinal stenosis underwent the MILD procedure. Ten patients were followed under an institutional review board-approved protocol designed to assess improvement in pain using a Visual Analog Scale (VAS), and disability using the Oswestry Disability Index (ODI). Preoperatively, these patients had ODI scores of 60%–80%, indicating that they were crippled by their condition, and VAS pain scores of 6–10.

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline (ODI 0%–20%) and the mean pain score decreased by 90% (VAS scores at 1). All 10 patients had discontinued narcotics use for pain by 6 weeks post op and were discharged from the hospital on the same day or the day following the procedure. “These are phenomenal results,” said Dr. Hirsch, who noted that these initial promising results must be validated by further study.

No complications have been reported from the procedure. Other advantages of the procedure are that it requires only local sedation, allows patients to recover quickly, and offers the possibility of delaying or preventing more invasive surgery. The incisions are smaller than a dime, said Dr. Hirsch, who presented his findings at the annual meeting of the Society of Neurointerventional Surgery and received travel support from the device's manufacturer, Vertos Medical Inc., of San Jose, Calif.

During an interview, Dr. Allan L. Brook, director of interventional neuroradiology at Montefiore Medical Center, New York, said he has used the MILD device in three cases. Montefiore is 1 of 10 sites participating in the Vertos-sponsored MILD Preliminary Patient Evaluation Study, a multicenter, prospective clinical study to assess the clinical application and outcomes of minimally invasive lumbar decompression with the devices in patients who have symptomatic spinal stenosis.

“These patients have had dramatic pain relief. The majority of these patients have exhausted standard medical therapies, as well as numerous other less invasive injections. I believe many patients could benefit from this minimally invasive posterior lumbar decompression,” said Dr. Brook. He noted that there are no other percutaneous procedures that attempt to remove the soft tissue that impinges from behind the nerves; most aim to remove the disk or rely upon open surgical techniques, with their known risks.

Dr. Brooks reported that he has no financial relationship with Vertos Medical.

“Lumbar spinal stenosis is a huge problem which really impacts people's quality of life. Approximately 1.5 million people in the U.S. are diagnosed with it every year—about twice the number of those who have vertebral compression fractures,” said Dr. Hirsch. “The MILD device allows us to provide a minimally invasive alternative to traditional laminectomy/laminotomy.”

In the first step, the bone rongeur is utilized to remove posterior bone.

A bone-removing device accesses ligamentum flavum.

The soft tissue rongeur removes ligament posterior to epidural space. Photos courtesy Dr. Allan L. Brook

At 6 weeks post treatment, the mean disability score improved by 84% compared with baseline. DR. HIRSH

NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Prednisone starting at 10 mg per day with a slow taper over 17 months was effective in controlling polymyalgia rheumatica in 93% of 189 elderly patients treated, based on a case series presented at the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica.

The regimen was associated with lower total steroid doses, fewer adverse events, and similar or fewer relapses and recurrences than have been seen in other series of patients given higher steroid doses.

The initial prednisone dose recommended for polymyalgia rheumatica (PMR) is 10–20 mg/day. In reality, the doses used generally are closer to 20 mg/day than to 10 mg/day, due to concerns about the risk of treatment failure, said Dr. Luis J. Catoggio, head of rheumatology at the Hospital Italiano de Buenos Aires. However, his analyses suggest that rapid tapering of the steroid, not a low initial dose, is associated with poor outcomes in PMR.

Dr. Catoggio reported on 209 patients (164 women) with PMR seen between 1983 and 2002 and treated with 10 mg of prednisone in single morning dose. The patients' mean age was 71 years. Median disease duration at diagnosis was 2 months. Median erythrocyte sedimentation rate (ESR) at baseline was 56 mm/hr.

The shoulder girdle and pelvic girdle were affected in 96% and 87%, respectively. The neck and torso were affected in 62%, and synovitis was present in 24%.

Prednisone was initiated at 10 mg/day or less in 189 patients (90%), 12.5–15 mg/day in 16 patients (8%), and over 15 mg/day in 7 patients (3%). Dr. Catoggio explained that patients given doses above 10 mg/day were initially treated at other centers. Median time to clinical response was 10 days. Median time to ESR of less than 30 mm/hr was 60 days.

Five of the 15 patients with initial treatment failures had started on prednisone doses of 7.5 mg/day and subsequently responded to 10 mg/day.

The other 10 had started on 10 mg/day and later responded to 15 mg/day. Three patients (1.4%) relapsed within 3 months of initiating therapy and 74 (35%) relapsed later. Median time to relapse was 15 months, and mean steroid dose at relapse was 4.3 mg/day.

By the data cutoff date, 95 patients (45%) had been able to discontinue treatment. Recurrences were seen in 22, with a median time to recurrence of 7 months, but 11 ultimately were able to discontinue their steroids. In patients who finally discontinued prednisone, median duration of treatment was 19 months.

The schedule that employs a 20 mg/day starting dosage sustains that dosage for 1 month. The dose is then tapered by 2.5 mg every 2 weeks unless symptoms recur. (For the 17-month schedule used at Dr. Catoggio's hospital, see chart.)

The 20 mg/day schedule represents a minimum treatment period of 4.5 months and a total steroid dose of 1,650 mg. It was initially successful in only 4 of 27 patients (15%) in one study. The remaining patients all required upward adjustment of their steroids or longer duration of therapy (Ann. Intern. Med. 1999;159:577–84).

Compared with another study where the mean cumulative dose was 8,400 mg, the mean total dose of prednisone in Dr. Catoggio's cohort was 2,900 mg.

Adverse events were seen in 49 patients (23%). These included vertebral fractures in 11, hip and other fractures in 4, cataracts in 7, and hyperglycemia in 5.

ELSEVIER GLOBAL MEDICAL NEWS

Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may help postpone the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage OA is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement. However, “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90 the difficulties are really serious,” he said, adding that in the Netherlands, approximately 1,000 total knee prostheses are placed each year in patients younger than 60.

“This is a major socioeconomic problem and will only grow with the aging of the population,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear. Then, springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of 100%—fell to 20%, while scores for function and clinical condition rose from 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

They next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and an increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

The overall conclusion is that joint distraction is clinically very effective in young patients with end-stage knee arthritis, with cartilage repair presumably responsible for the clinical benefit, he said. However, more prolonged follow-up is needed.

Some of the ankle patients have had a second distraction, but whether this will be feasible and advisable in the knee patients remains to be seen, because the follow-up is too short.

“It may be possible, and of course we hope [that] it's not just a delay before joint replacement, but that we can really cure the joint. That's only wishful thinking so far, though,” he said.

Dr. Lafeber acknowledged that his study was not placebo controlled.

“Of course it would be better to have a good control, which in this case would be placement of the complete frame but without the distraction,” he said.

Currently, however, they are offering this treatment only to patients with end-stage OA who otherwise would be considered for joint replacement. “We cannot ethically allow these patients to go without any treatment for 2 years,” he said.

Moreover, with benefits persisting for up to 10 years for the ankle patients, placebo effects are hardly likely to still be in play. “Maybe for the first year, because these patients are seeing their physicians more frequently than they would otherwise, but certainly after several years the placebo effect would have vanished,” he said.

This knee has OA at baseline on x-ray (top). Cartilage repaired itself after 2 years of treatment (bottom). Distraction may alleviate the need for total knee arthroplasty. Photos courtesy Dr. Floris P.J.G. Lafeber

Biomarkers of bone breakdown and synthesis increase during distraction. Courtesy Dr. Floris P.J.G. Lafeber

Iowa's Experience With Ankle OA

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

The study, funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic OA of the ankle. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or with the addition of continuous passive joint motion.

Patients have been evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the non-motion group.

“I think this is quite an intriguing technique,” Dr. Amendola said.

Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may help postpone the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage OA is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement. However, “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90 the difficulties are really serious,” he said, adding that in the Netherlands, approximately 1,000 total knee prostheses are placed each year in patients younger than 60.

“This is a major socioeconomic problem and will only grow with the aging of the population,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear. Then, springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of 100%—fell to 20%, while scores for function and clinical condition rose from 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

They next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and an increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

The overall conclusion is that joint distraction is clinically very effective in young patients with end-stage knee arthritis, with cartilage repair presumably responsible for the clinical benefit, he said. However, more prolonged follow-up is needed.

Some of the ankle patients have had a second distraction, but whether this will be feasible and advisable in the knee patients remains to be seen, because the follow-up is too short.

“It may be possible, and of course we hope [that] it's not just a delay before joint replacement, but that we can really cure the joint. That's only wishful thinking so far, though,” he said.

Dr. Lafeber acknowledged that his study was not placebo controlled.

“Of course it would be better to have a good control, which in this case would be placement of the complete frame but without the distraction,” he said.

Currently, however, they are offering this treatment only to patients with end-stage OA who otherwise would be considered for joint replacement. “We cannot ethically allow these patients to go without any treatment for 2 years,” he said.

Moreover, with benefits persisting for up to 10 years for the ankle patients, placebo effects are hardly likely to still be in play. “Maybe for the first year, because these patients are seeing their physicians more frequently than they would otherwise, but certainly after several years the placebo effect would have vanished,” he said.

This knee has OA at baseline on x-ray (top). Cartilage repaired itself after 2 years of treatment (bottom). Distraction may alleviate the need for total knee arthroplasty. Photos courtesy Dr. Floris P.J.G. Lafeber

Biomarkers of bone breakdown and synthesis increase during distraction. Courtesy Dr. Floris P.J.G. Lafeber

Iowa's Experience With Ankle OA

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

The study, funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic OA of the ankle. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or with the addition of continuous passive joint motion.

Patients have been evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the non-motion group.

“I think this is quite an intriguing technique,” Dr. Amendola said.

Joint distraction, a surgical technique that involves the placement of an external fixation frame around a degenerated joint, may help postpone the need for total knee replacement in young patients with severe osteoarthritis.

The cartilage in end-stage OA is severely damaged, with fissuring; altered chondrocyte distribution and death; and a significant loss of extracellular matrix constituents. These changes in cartilage are accompanied by characteristic changes in periarticular bone and soft tissue. All these structural changes mean severe pain and functional limitations for patients, who typically rate their pain with a score of 80% out of a maximum of 100%, according to Dr. Floris P.J.G. Lafeber, of the University Medical Center Utrecht (the Netherlands).

The standard treatment for these patients is total knee replacement. However, “Total knee prostheses don't last forever,” Dr. Lafeber said. “They last on average 15 years, so if you have one placed at age 60 you are likely to need a replacement at 75, which is complicated and expensive, and the results are often disappointing. And then if you need another at age 90 the difficulties are really serious,” he said, adding that in the Netherlands, approximately 1,000 total knee prostheses are placed each year in patients younger than 60.

“This is a major socioeconomic problem and will only grow with the aging of the population,” he said.

The rationale for joint distraction lies in the hypothesis that osteoarthritic cartilage is capable of self-repair if the joint is unloaded and chondrocyte nutrition is maintained. Pins are drilled through the soft tissue and bone just above and below the joint, and when the frame is in place the distance between the cartilaginous surfaces of the joint is increased by 5 mm. This transfers the load and stresses on cartilage away from the joint, eliminating further wear and tear. Then, springs within the distraction frame cause changes to occur in fluid pressure in the joint, with increases during loading and normalization with unloading. This continuous change in fluid pressure is important for the cartilage, because chondrocytes depend on synovial flow for nutrition, Dr. Lafeber explained.

The loading onto the frame also results in periarticular osteopenia, which in turn permits the sclerotic, osteoarthritic bone to become more flexible and the mineral content to normalize once the frame is removed. Furthermore, the periarticular bone turnover results in the release of multiple growth factors that can help repair the cartilage.

In collaboration with his center's orthopedic department, Dr. Lafeber and his colleagues in the department of rheumatology and clinical immunology began exploring this technique in a proof-of-concept study with ankle distraction. Although ankle OA is much less common than knee OA, in the case of failure an arthrodesis could be performed without much risk, he said.

A total of 73 patients underwent ankle distraction for 3 months, with the result that pain scores—rated at an average of 75% of 100%—fell to 20%, while scores for function and clinical condition rose from 25% at baseline to 80%. Some of these patients now have been followed for as long as 10 years, with continuing benefits.

They next did a feasibility study that included three patients with knee OA, and found similar results on pain and function scores as well as on stiffness scores. They then undertook a larger prospective study in which 19 patients with severe knee OA (mean age, 48 years) have been treated with 2-month periods of distraction. Thus far, six have been followed for up to 2 years. Functional ability and clinical condition, poor at the onset with scores of 39% and 32%, respectively, increased to 82% and 81%.

Serum and urinary biomarkers of cartilage turnover were measured throughout a 12-month follow-up. During the distraction phase there was an enormous turnover, with elevations of markers of both synthesis and breakdown, but after the distraction phase there was a gradual decrease of breakdown markers and an increase in the markers of synthesis, indicating repair of the cartilage, Dr. Lafeber said.

Imaging studies also demonstrated improvements. In seven patients who have been followed for more than 12 months, joint space width shown on x-rays increased from slightly greater than 2.5 mm to more than 3.5 mm. “And on MRI studies done after 1 year and read in a blinded fashion in collaboration with Prof. Felix Eckstein, who is one of the leading researchers in this field, the amount of subchondral bone covered with cartilage was shown to have increased by 40%, cartilage volume increased by 50%, and cartilage thickness over the bone increased by 5%,” Dr. Lafeber said.

The overall conclusion is that joint distraction is clinically very effective in young patients with end-stage knee arthritis, with cartilage repair presumably responsible for the clinical benefit, he said. However, more prolonged follow-up is needed.

Some of the ankle patients have had a second distraction, but whether this will be feasible and advisable in the knee patients remains to be seen, because the follow-up is too short.

“It may be possible, and of course we hope [that] it's not just a delay before joint replacement, but that we can really cure the joint. That's only wishful thinking so far, though,” he said.

Dr. Lafeber acknowledged that his study was not placebo controlled.

“Of course it would be better to have a good control, which in this case would be placement of the complete frame but without the distraction,” he said.

Currently, however, they are offering this treatment only to patients with end-stage OA who otherwise would be considered for joint replacement. “We cannot ethically allow these patients to go without any treatment for 2 years,” he said.

Moreover, with benefits persisting for up to 10 years for the ankle patients, placebo effects are hardly likely to still be in play. “Maybe for the first year, because these patients are seeing their physicians more frequently than they would otherwise, but certainly after several years the placebo effect would have vanished,” he said.

This knee has OA at baseline on x-ray (top). Cartilage repaired itself after 2 years of treatment (bottom). Distraction may alleviate the need for total knee arthroplasty. Photos courtesy Dr. Floris P.J.G. Lafeber

Biomarkers of bone breakdown and synthesis increase during distraction. Courtesy Dr. Floris P.J.G. Lafeber

Iowa's Experience With Ankle OA

Ankle distraction also has been performed and is being evaluated in a randomized study led by Dr. Annunziato Amendola of the University of Iowa, Iowa City.

The study, funded by the National Institutes of Health, prospectively enrolled about 40 patients with posttraumatic OA of the ankle. They used the same ankle distraction technique as did Dr. Lafeber's group, but patients were randomized to distraction alone or with the addition of continuous passive joint motion.

Patients have been evaluated clinically and radiographically, and with a special three-dimensional CT scanning technique to look at cartilage regeneration.

All but three patients have now undergone 2- and 3-year evaluations, and the results thus far have been comparable to the results they have had in Utrecht in terms of relief of pain, according to Dr. Amendola. Additional improvements have been seen over time, and patients in the motion group did significantly better at every time point than did the non-motion group.

“I think this is quite an intriguing technique,” Dr. Amendola said.

PARIS — Pain is paramount to rheumatoid arthritis patients, according to a European League Against Rheumatism survey of 505 RA patients in 10 European countries. The survey was reported by Dr. Tore K. Kvien at the annual European Congress of Rheumatology.

The finding came from a new measure, the Rheumatoid Arthritis Impact of Disease (RAID) score, created by a EULAR task force to make up for the deficiencies in the current widely used indices of disease activity—for example, the Disease Activity Score—which don't include all of the outcomes patients deem important, such as fatigue, added Dr. Kvien, professor of rheumatology at the University of Oslo and editor of the Annals of Rheumatic Diseases.

The RAID score began with a group of 10 patients who developed a list of 17 domains important to patients with RA. This list was trimmed to 7 through a subsequent survey in which 10 patients from each of 10 European countries ranked the 17 domains.

Next, 505 RA patients in 10 countries were asked to rank the relative importance of the seven domains. Pain got 23 points; function, 16; fatigue, 16; emotional well-being, 11; sleep, 11; coping, 11; and physical well-being, 11. The weighted values were unaffected by disease duration or severity level, meaning the weighting system has a desirably high generalizability.

Dr. Kvien then relied upon an extensive review of the psychometric literature and expert opinion to create the RAID questionnaire, which includes rating scales and other assessments addressing each of the seven weighted domains.

The RAID score is currently undergoing a 12-country validation study that will refine the final wording choices. After that, physicians are likely to increasingly encounter RAID as a prespecified end point in clinical trials.

PARIS — Pain is paramount to rheumatoid arthritis patients, according to a European League Against Rheumatism survey of 505 RA patients in 10 European countries. The survey was reported by Dr. Tore K. Kvien at the annual European Congress of Rheumatology.

The finding came from a new measure, the Rheumatoid Arthritis Impact of Disease (RAID) score, created by a EULAR task force to make up for the deficiencies in the current widely used indices of disease activity—for example, the Disease Activity Score—which don't include all of the outcomes patients deem important, such as fatigue, added Dr. Kvien, professor of rheumatology at the University of Oslo and editor of the Annals of Rheumatic Diseases.

The RAID score began with a group of 10 patients who developed a list of 17 domains important to patients with RA. This list was trimmed to 7 through a subsequent survey in which 10 patients from each of 10 European countries ranked the 17 domains.

Next, 505 RA patients in 10 countries were asked to rank the relative importance of the seven domains. Pain got 23 points; function, 16; fatigue, 16; emotional well-being, 11; sleep, 11; coping, 11; and physical well-being, 11. The weighted values were unaffected by disease duration or severity level, meaning the weighting system has a desirably high generalizability.

Dr. Kvien then relied upon an extensive review of the psychometric literature and expert opinion to create the RAID questionnaire, which includes rating scales and other assessments addressing each of the seven weighted domains.

The RAID score is currently undergoing a 12-country validation study that will refine the final wording choices. After that, physicians are likely to increasingly encounter RAID as a prespecified end point in clinical trials.

PARIS — Pain is paramount to rheumatoid arthritis patients, according to a European League Against Rheumatism survey of 505 RA patients in 10 European countries. The survey was reported by Dr. Tore K. Kvien at the annual European Congress of Rheumatology.

The finding came from a new measure, the Rheumatoid Arthritis Impact of Disease (RAID) score, created by a EULAR task force to make up for the deficiencies in the current widely used indices of disease activity—for example, the Disease Activity Score—which don't include all of the outcomes patients deem important, such as fatigue, added Dr. Kvien, professor of rheumatology at the University of Oslo and editor of the Annals of Rheumatic Diseases.

The RAID score began with a group of 10 patients who developed a list of 17 domains important to patients with RA. This list was trimmed to 7 through a subsequent survey in which 10 patients from each of 10 European countries ranked the 17 domains.

Next, 505 RA patients in 10 countries were asked to rank the relative importance of the seven domains. Pain got 23 points; function, 16; fatigue, 16; emotional well-being, 11; sleep, 11; coping, 11; and physical well-being, 11. The weighted values were unaffected by disease duration or severity level, meaning the weighting system has a desirably high generalizability.

Dr. Kvien then relied upon an extensive review of the psychometric literature and expert opinion to create the RAID questionnaire, which includes rating scales and other assessments addressing each of the seven weighted domains.

The RAID score is currently undergoing a 12-country validation study that will refine the final wording choices. After that, physicians are likely to increasingly encounter RAID as a prespecified end point in clinical trials.

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial.

The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“In this small study, tolerability is not affected by doubling the dosage in patients not reaching target levels,” study investigator Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen (the Netherlands), said in an interview.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment.

But solubility drops dramatically with lower temperature, and so lower serum urate values are needed.

A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in the interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

The gout diagnosis was confirmed by microscopic evidence of urate crystals in punctate from synovial fluid or periarticular structures or presence of tophi. The patients were indicated for serum urate-lowering treatment if they had tophi or more than two gout attacks per year. None of the patients had relevant liver or renal disease, and none had previously received either medication. Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%).

After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Even before the dose increase, two patients stopped taking allopurinol and three stopped taking benzbromarone because of adverse drug reactions.

No more adverse reactions occurred after the dosages were increased in the nonresponders.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial.

The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“In this small study, tolerability is not affected by doubling the dosage in patients not reaching target levels,” study investigator Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen (the Netherlands), said in an interview.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment.

But solubility drops dramatically with lower temperature, and so lower serum urate values are needed.

A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in the interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

The gout diagnosis was confirmed by microscopic evidence of urate crystals in punctate from synovial fluid or periarticular structures or presence of tophi. The patients were indicated for serum urate-lowering treatment if they had tophi or more than two gout attacks per year. None of the patients had relevant liver or renal disease, and none had previously received either medication. Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%).

After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Even before the dose increase, two patients stopped taking allopurinol and three stopped taking benzbromarone because of adverse drug reactions.

No more adverse reactions occurred after the dosages were increased in the nonresponders.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

Gout patients have equal rates of success in attaining a serum urate concentration of 0.30 mmol/L or less—a value thought to predict good control of flares and a reduction of tophi—with either allopurinol or benzbromarone, as long as the doses are slightly higher than normal and based on serum urate values, according to the results of a randomized, open-label trial.

The data were presented at the annual meeting of the European League Against Rheumatism in Paris.

“In this small study, tolerability is not affected by doubling the dosage in patients not reaching target levels,” study investigator Mattheus Reinders, a hospital pharmacist at the Atrium Medisch Centrum, Heerlen (the Netherlands), said in an interview.

The results of the study make it clear that there is no difference in efficacy between allopurinol and benzbromarone when given in adequate doses, despite their different mechanisms of action. It also shows “allopurinol must be dosed higher than usually done in trials and in clinical practice [300 mg/day] to reach target serum levels,” Mr. Reinders said.

Gout flares and tophi mostly occur in those body parts with the lowest temperature: the extremities. It is often said that serum urate (uric acid) concentration—a well-accepted biomarker for evaluation of gout treatment—must be lower than the solubility at 37 °C (0.42 mmol/L) for good treatment.

But solubility drops dramatically with lower temperature, and so lower serum urate values are needed.

A serum urate concentration of 0.30 mmol/L or lower has been shown to be adequate in previous research, Mr. Reinders said in the interview.

EULAR's evidence-based recommendations for gout advise titrating the allopurinol dosage according to the level of serum urate that is attained. There is a lack of information about this approach and the effects of the higher dosages of serum urate-lowering drugs that will be required to decrease serum urate in patients who are not reaching target levels. Many clinicians also are prescribing only a fixed dosage of allopurinol 300 mg/day, he said.

Therefore, Mr. Reinders and his coinvestigators randomized 55 patients with newly diagnosed gout in an open-label trial comparing the efficacy and tolerability of allopurinol and benzbromarone. Allopurinol began at a dosage of 300 mg/day and was increased to 600 mg/day if necessary, while benzbromarone started at 100 mg/day and could be increased to 200 mg/day.

The gout diagnosis was confirmed by microscopic evidence of urate crystals in punctate from synovial fluid or periarticular structures or presence of tophi. The patients were indicated for serum urate-lowering treatment if they had tophi or more than two gout attacks per year. None of the patients had relevant liver or renal disease, and none had previously received either medication. Mr. Reinders conducted the research when he was in training at the Medisch Centrum Leeuwarden, also in the Netherlands, which funded the study.

After 2 months of treatment, a significantly greater percentage of patients who took benzbromarone 100 mg/day reached the target serum urate concentration of 0.30 mmol/L (13 of 25 patients, or 52%) than did patients who took allopurinol 300 mg/day (8 of 30 patients, or 27%).

After the investigators doubled the daily dosage of each drug in patients who had not met the treatment target, there was no significant difference in the total percentage of patients who had successful treatment with allopurinol (21 of 27, or 78%), compared with benzbromarone (18 of 23, or 78%).

Even before the dose increase, two patients stopped taking allopurinol and three stopped taking benzbromarone because of adverse drug reactions.

No more adverse reactions occurred after the dosages were increased in the nonresponders.

'Allopurinol must be dosed higher than usually done in trials and in clinical practice to reach target serum levels.' MR. REINDERS

PARIS — The investigational long-acting interleukin-1 inhibitor rilonacept showed potential as an important new treatment option in patients with severe refractory chronic active gout in a small pilot study, according to a rheumatologist whose research focus is chronic gout.

Five of 10 patients in the single-blind nonrandomized study showed at least a 75% improvement in pain scores after 6 weekly subcutaneous injections of rilonacept at a fixed dose of 160 mg.

These were patients with severe refractory pain and disability at baseline, and none of them responded to 2 weeks of placebo injections, commented Dr. John S. Sundy, the director of rheumatology and allergy research at the Duke Clinical Research Institute, Duke University, Durham, N.C.

He disclosed that he is a consultant to Regeneron Pharmaceuticals Inc., which sponsored the pilot study.

Rilonacept is a soluble dimeric fusion protein and high-affinity blocker of the interleukin-1 receptor type 1 and the IL-1 accessory protein. Its therapeutic efficacy in this multicenter proof-of-concept study reinforces preclinical evidence and a small case series suggesting that IL-1 plays an important role in gouty inflammation, and that blockade of the IL-1 pathway represents a new treatment strategy in gouty arthritis.

The pathophysiologic sequence involves the engulfing of monosodium urate crystals by monocytes, which activates the cryopyrin inflammasome with resultant release of IL-1 into surrounding tissues.

The IL-1β induces expression of chemokines and adhesion molecules, which draw polymorphonuclear leukocytes to the site of acute inflammation, thereby making the inflamed joint even hotter, he explained.

The 10 participants in the pilot study had a mean age of 62 years, a 13-year history of gout, and a mean visual analog scale pain score of 5.1 at enrollment.

The patients had a mean of nearly three actively inflamed joints for at least the past month at enrollment.

Standard gout therapies were either ineffective or laden with unacceptable side effects in this overweight/obese population with numerous comorbid conditions.

High-sensitivity C-reactive protein levels (a measure of disease activity) dropped by an average of 59% after 6 weeks of rilonacept, then trended back up toward baseline during 6 weeks of follow-up off the drug. The number of affected joints decreased during active treatment, a trend that just missed statistical significance in this small study.

The same was true for physicians' global ratings.

Rilonacept was generally well tolerated. The most common reported side effect consisted of mild to moderate injection site reactions.

Speaking at the annual European Congress of Rheumatology, Dr. Sundy said that in addition to much larger and longer-term placebo-controlled trials of rilonacept in refractory chronic active gout, other trials are planned or underway to evaluate the IL-1 inhibitor for prevention of acute flares in patients with chronic gout, as well as in other inflammatory diseases in which the IL-1 pathway is believed to figure prominently.

These include juvenile idiopathic arthritis, familial Mediterranean fever, and rheumatoid arthritis.

Earlier this year, rilonacept received Food and Drug Administration marketing approval for the treatment of two rare cryopyrin-associated periodic syndromes: Muckle-Wells syndrome and familial cold autoinflammatory syndrome.

One audience member indicated that he wasn't bowled over by the 50% response rate reported by Dr. Sundy.

He questioned the merits of developing a sophisticated and costly new therapy for a familiar disease for which far simpler alternatives—including intra-articular corticosteroid injections—are often highly effective.

Dr. Sundy replied that rilonacept is targeted at the minority of patients in whom tried-and-true therapies aren't effective or are intolerable.

Given that gout is the most common inflammatory arthritis in men and its incidence is climbing, that's not an insignificant number of patients.

“This is the severe end of the spectrum of gout. It's the small tail on the curve, not the typical everyday presentation of gout,” he stressed.

PARIS — The investigational long-acting interleukin-1 inhibitor rilonacept showed potential as an important new treatment option in patients with severe refractory chronic active gout in a small pilot study, according to a rheumatologist whose research focus is chronic gout.

Five of 10 patients in the single-blind nonrandomized study showed at least a 75% improvement in pain scores after 6 weekly subcutaneous injections of rilonacept at a fixed dose of 160 mg.

These were patients with severe refractory pain and disability at baseline, and none of them responded to 2 weeks of placebo injections, commented Dr. John S. Sundy, the director of rheumatology and allergy research at the Duke Clinical Research Institute, Duke University, Durham, N.C.

He disclosed that he is a consultant to Regeneron Pharmaceuticals Inc., which sponsored the pilot study.

Rilonacept is a soluble dimeric fusion protein and high-affinity blocker of the interleukin-1 receptor type 1 and the IL-1 accessory protein. Its therapeutic efficacy in this multicenter proof-of-concept study reinforces preclinical evidence and a small case series suggesting that IL-1 plays an important role in gouty inflammation, and that blockade of the IL-1 pathway represents a new treatment strategy in gouty arthritis.

The pathophysiologic sequence involves the engulfing of monosodium urate crystals by monocytes, which activates the cryopyrin inflammasome with resultant release of IL-1 into surrounding tissues.

The IL-1β induces expression of chemokines and adhesion molecules, which draw polymorphonuclear leukocytes to the site of acute inflammation, thereby making the inflamed joint even hotter, he explained.

The 10 participants in the pilot study had a mean age of 62 years, a 13-year history of gout, and a mean visual analog scale pain score of 5.1 at enrollment.

The patients had a mean of nearly three actively inflamed joints for at least the past month at enrollment.

Standard gout therapies were either ineffective or laden with unacceptable side effects in this overweight/obese population with numerous comorbid conditions.

High-sensitivity C-reactive protein levels (a measure of disease activity) dropped by an average of 59% after 6 weeks of rilonacept, then trended back up toward baseline during 6 weeks of follow-up off the drug. The number of affected joints decreased during active treatment, a trend that just missed statistical significance in this small study.

The same was true for physicians' global ratings.

Rilonacept was generally well tolerated. The most common reported side effect consisted of mild to moderate injection site reactions.

Speaking at the annual European Congress of Rheumatology, Dr. Sundy said that in addition to much larger and longer-term placebo-controlled trials of rilonacept in refractory chronic active gout, other trials are planned or underway to evaluate the IL-1 inhibitor for prevention of acute flares in patients with chronic gout, as well as in other inflammatory diseases in which the IL-1 pathway is believed to figure prominently.

These include juvenile idiopathic arthritis, familial Mediterranean fever, and rheumatoid arthritis.

Earlier this year, rilonacept received Food and Drug Administration marketing approval for the treatment of two rare cryopyrin-associated periodic syndromes: Muckle-Wells syndrome and familial cold autoinflammatory syndrome.

One audience member indicated that he wasn't bowled over by the 50% response rate reported by Dr. Sundy.

He questioned the merits of developing a sophisticated and costly new therapy for a familiar disease for which far simpler alternatives—including intra-articular corticosteroid injections—are often highly effective.

Dr. Sundy replied that rilonacept is targeted at the minority of patients in whom tried-and-true therapies aren't effective or are intolerable.

Given that gout is the most common inflammatory arthritis in men and its incidence is climbing, that's not an insignificant number of patients.

“This is the severe end of the spectrum of gout. It's the small tail on the curve, not the typical everyday presentation of gout,” he stressed.

PARIS — The investigational long-acting interleukin-1 inhibitor rilonacept showed potential as an important new treatment option in patients with severe refractory chronic active gout in a small pilot study, according to a rheumatologist whose research focus is chronic gout.

Five of 10 patients in the single-blind nonrandomized study showed at least a 75% improvement in pain scores after 6 weekly subcutaneous injections of rilonacept at a fixed dose of 160 mg.

These were patients with severe refractory pain and disability at baseline, and none of them responded to 2 weeks of placebo injections, commented Dr. John S. Sundy, the director of rheumatology and allergy research at the Duke Clinical Research Institute, Duke University, Durham, N.C.

He disclosed that he is a consultant to Regeneron Pharmaceuticals Inc., which sponsored the pilot study.

Rilonacept is a soluble dimeric fusion protein and high-affinity blocker of the interleukin-1 receptor type 1 and the IL-1 accessory protein. Its therapeutic efficacy in this multicenter proof-of-concept study reinforces preclinical evidence and a small case series suggesting that IL-1 plays an important role in gouty inflammation, and that blockade of the IL-1 pathway represents a new treatment strategy in gouty arthritis.

The pathophysiologic sequence involves the engulfing of monosodium urate crystals by monocytes, which activates the cryopyrin inflammasome with resultant release of IL-1 into surrounding tissues.

The IL-1β induces expression of chemokines and adhesion molecules, which draw polymorphonuclear leukocytes to the site of acute inflammation, thereby making the inflamed joint even hotter, he explained.

The 10 participants in the pilot study had a mean age of 62 years, a 13-year history of gout, and a mean visual analog scale pain score of 5.1 at enrollment.

The patients had a mean of nearly three actively inflamed joints for at least the past month at enrollment.

Standard gout therapies were either ineffective or laden with unacceptable side effects in this overweight/obese population with numerous comorbid conditions.

High-sensitivity C-reactive protein levels (a measure of disease activity) dropped by an average of 59% after 6 weeks of rilonacept, then trended back up toward baseline during 6 weeks of follow-up off the drug. The number of affected joints decreased during active treatment, a trend that just missed statistical significance in this small study.

The same was true for physicians' global ratings.

Rilonacept was generally well tolerated. The most common reported side effect consisted of mild to moderate injection site reactions.

Speaking at the annual European Congress of Rheumatology, Dr. Sundy said that in addition to much larger and longer-term placebo-controlled trials of rilonacept in refractory chronic active gout, other trials are planned or underway to evaluate the IL-1 inhibitor for prevention of acute flares in patients with chronic gout, as well as in other inflammatory diseases in which the IL-1 pathway is believed to figure prominently.

These include juvenile idiopathic arthritis, familial Mediterranean fever, and rheumatoid arthritis.

Earlier this year, rilonacept received Food and Drug Administration marketing approval for the treatment of two rare cryopyrin-associated periodic syndromes: Muckle-Wells syndrome and familial cold autoinflammatory syndrome.

One audience member indicated that he wasn't bowled over by the 50% response rate reported by Dr. Sundy.

He questioned the merits of developing a sophisticated and costly new therapy for a familiar disease for which far simpler alternatives—including intra-articular corticosteroid injections—are often highly effective.

Dr. Sundy replied that rilonacept is targeted at the minority of patients in whom tried-and-true therapies aren't effective or are intolerable.

Given that gout is the most common inflammatory arthritis in men and its incidence is climbing, that's not an insignificant number of patients.

“This is the severe end of the spectrum of gout. It's the small tail on the curve, not the typical everyday presentation of gout,” he stressed.

PARIS — Factors that predict which rheumatoid arthritis patients will achieve and maintain remission after disease-modifying drugs include low body mass index, low erythrocyte sedimentation rate levels, and absence of anti-cyclic citrullinated peptide antibody at baseline.

“Remission is increasingly becoming an attainable goal in rheumatoid arthritis treatment, and it would be useful to be able to predict which patients are likely to achieve remission in the long run, and so to be able to avoid overly aggressive treatment,” Dr. Diane van der Woude said at the annual European Congress of Rheumatology.

Although factors have been identified that predict the achievement of very low disease activity with biologics, little is known about the predictive factors of patients treated with DMARDs, said Dr. van der Woude of the department of rheumatology at Leiden (the Netherlands) University Medical Center.

She analyzed clinical, laboratory, and genetic data from patients enrolled in an inception cohort at the Leiden Early Arthritis Clinic between 1993 and 2003.

Among more than 1,900 patients referred to the clinic, 454 were diagnosed with RA and treated with chloroquine, sulfasalazine, or methotrexate, she said.

Sustained remission, or the absence of synovitis for longer than 1 year without DMARDs, was achieved by 69 patients (15%) with an average follow-up of 8 years. Six patients discharged because of remission had a recurrence of synovitis and were excluded from the remission group.

Univariate analysis revealed the following were significantly associated with less likelihood of achieving DMARD-free remission: positive family history (hazard ratio 0.56); high body mass index (HR 0.90); long duration of symptoms at presentation (HR 0.93); smoking (HR 0.55); and the presence of IgM rheumatoid factor (HR 0.17), anti-cyclic citrullinated peptide (CCP) antibodies (HR 0.09), and shared epitope alleles (HR 0.47).

Multivariate analysis identified older age, low BMI, low ESR, short duration of symptoms, nonsmoking status, and the absence of anti-CCP antibodies as independent predictors for DMARD-free remission.

PARIS — Factors that predict which rheumatoid arthritis patients will achieve and maintain remission after disease-modifying drugs include low body mass index, low erythrocyte sedimentation rate levels, and absence of anti-cyclic citrullinated peptide antibody at baseline.

“Remission is increasingly becoming an attainable goal in rheumatoid arthritis treatment, and it would be useful to be able to predict which patients are likely to achieve remission in the long run, and so to be able to avoid overly aggressive treatment,” Dr. Diane van der Woude said at the annual European Congress of Rheumatology.

Although factors have been identified that predict the achievement of very low disease activity with biologics, little is known about the predictive factors of patients treated with DMARDs, said Dr. van der Woude of the department of rheumatology at Leiden (the Netherlands) University Medical Center.

She analyzed clinical, laboratory, and genetic data from patients enrolled in an inception cohort at the Leiden Early Arthritis Clinic between 1993 and 2003.

Among more than 1,900 patients referred to the clinic, 454 were diagnosed with RA and treated with chloroquine, sulfasalazine, or methotrexate, she said.

Sustained remission, or the absence of synovitis for longer than 1 year without DMARDs, was achieved by 69 patients (15%) with an average follow-up of 8 years. Six patients discharged because of remission had a recurrence of synovitis and were excluded from the remission group.

Univariate analysis revealed the following were significantly associated with less likelihood of achieving DMARD-free remission: positive family history (hazard ratio 0.56); high body mass index (HR 0.90); long duration of symptoms at presentation (HR 0.93); smoking (HR 0.55); and the presence of IgM rheumatoid factor (HR 0.17), anti-cyclic citrullinated peptide (CCP) antibodies (HR 0.09), and shared epitope alleles (HR 0.47).

Multivariate analysis identified older age, low BMI, low ESR, short duration of symptoms, nonsmoking status, and the absence of anti-CCP antibodies as independent predictors for DMARD-free remission.

PARIS — Factors that predict which rheumatoid arthritis patients will achieve and maintain remission after disease-modifying drugs include low body mass index, low erythrocyte sedimentation rate levels, and absence of anti-cyclic citrullinated peptide antibody at baseline.

“Remission is increasingly becoming an attainable goal in rheumatoid arthritis treatment, and it would be useful to be able to predict which patients are likely to achieve remission in the long run, and so to be able to avoid overly aggressive treatment,” Dr. Diane van der Woude said at the annual European Congress of Rheumatology.

Although factors have been identified that predict the achievement of very low disease activity with biologics, little is known about the predictive factors of patients treated with DMARDs, said Dr. van der Woude of the department of rheumatology at Leiden (the Netherlands) University Medical Center.

She analyzed clinical, laboratory, and genetic data from patients enrolled in an inception cohort at the Leiden Early Arthritis Clinic between 1993 and 2003.

Among more than 1,900 patients referred to the clinic, 454 were diagnosed with RA and treated with chloroquine, sulfasalazine, or methotrexate, she said.

Sustained remission, or the absence of synovitis for longer than 1 year without DMARDs, was achieved by 69 patients (15%) with an average follow-up of 8 years. Six patients discharged because of remission had a recurrence of synovitis and were excluded from the remission group.

Univariate analysis revealed the following were significantly associated with less likelihood of achieving DMARD-free remission: positive family history (hazard ratio 0.56); high body mass index (HR 0.90); long duration of symptoms at presentation (HR 0.93); smoking (HR 0.55); and the presence of IgM rheumatoid factor (HR 0.17), anti-cyclic citrullinated peptide (CCP) antibodies (HR 0.09), and shared epitope alleles (HR 0.47).

Multivariate analysis identified older age, low BMI, low ESR, short duration of symptoms, nonsmoking status, and the absence of anti-CCP antibodies as independent predictors for DMARD-free remission.