Rheumatoid Arthritis

BEVERLY HILLS, CALIF. — New ideas about the causes of osteoarthritis may lead to targeted therapeutic advances like those currently available for rheumatoid arthritis, Dr. Steven R. Ytterberg said at the annual meeting of the American Association for Hand Surgery.

The first conceptual shift is the notion that osteoarthritis probably is not a disease, but a clinical and pathologic outcome arising from a range of disorders, explained Dr. Ytterberg, a clinical rheumatologist and researcher at the Mayo Clinic, Rochester, Minn.

He noted wide disparities in the characteristics of primary vs. secondary osteoarthritis; localized, single-joint disease vs. generalized osteoarthritis; and osteoarthritis associated with osteophyte necrosis, inflammation, or crystal deposition. Dr. Ytterberg compared, for instance, inflammatory, erosive osteoarthritis of the hands with diffuse idiopathic skeletal hyperostosis (DISH).

“Is this all the same disease? I don't know that it makes sense that it is,” he said.

Another major shift is in the way researchers are studying development of osteoarthritis.

“With osteoarthritis, the focus has always been on cartilage. To begin to see frayed cartilage through the arthroscope has always been presumed to be where the action is.”

Microscopic disruption of the extracellular matrix, and later, macroscopic clefts in the cartilage were seen as progressive evidence of encroaching disease.

Now, the focus has shifted, and the target of research is bone. “A large amount of information is now calling attention to what's going on in the chondrocytes: potential changes in cell-signaling pathways,” he said.

Many researchers are now beginning to believe that “subchondral bone is where the problem is,” with cartilage abnormalities perhaps the downstream effect of abnormal wear in response to bone changes, said Dr. Ytterberg.

Others are pursuing the hypothesis that osteoarthritis is an enthesopathy.

These theories, still in their infancy, could one day help characterize a diffusely defined symptom set that may or may not have common origins, he said.

BEVERLY HILLS, CALIF. — New ideas about the causes of osteoarthritis may lead to targeted therapeutic advances like those currently available for rheumatoid arthritis, Dr. Steven R. Ytterberg said at the annual meeting of the American Association for Hand Surgery.

The first conceptual shift is the notion that osteoarthritis probably is not a disease, but a clinical and pathologic outcome arising from a range of disorders, explained Dr. Ytterberg, a clinical rheumatologist and researcher at the Mayo Clinic, Rochester, Minn.

He noted wide disparities in the characteristics of primary vs. secondary osteoarthritis; localized, single-joint disease vs. generalized osteoarthritis; and osteoarthritis associated with osteophyte necrosis, inflammation, or crystal deposition. Dr. Ytterberg compared, for instance, inflammatory, erosive osteoarthritis of the hands with diffuse idiopathic skeletal hyperostosis (DISH).

“Is this all the same disease? I don't know that it makes sense that it is,” he said.

Another major shift is in the way researchers are studying development of osteoarthritis.

“With osteoarthritis, the focus has always been on cartilage. To begin to see frayed cartilage through the arthroscope has always been presumed to be where the action is.”

Microscopic disruption of the extracellular matrix, and later, macroscopic clefts in the cartilage were seen as progressive evidence of encroaching disease.

Now, the focus has shifted, and the target of research is bone. “A large amount of information is now calling attention to what's going on in the chondrocytes: potential changes in cell-signaling pathways,” he said.

Many researchers are now beginning to believe that “subchondral bone is where the problem is,” with cartilage abnormalities perhaps the downstream effect of abnormal wear in response to bone changes, said Dr. Ytterberg.

Others are pursuing the hypothesis that osteoarthritis is an enthesopathy.

These theories, still in their infancy, could one day help characterize a diffusely defined symptom set that may or may not have common origins, he said.

BEVERLY HILLS, CALIF. — New ideas about the causes of osteoarthritis may lead to targeted therapeutic advances like those currently available for rheumatoid arthritis, Dr. Steven R. Ytterberg said at the annual meeting of the American Association for Hand Surgery.

The first conceptual shift is the notion that osteoarthritis probably is not a disease, but a clinical and pathologic outcome arising from a range of disorders, explained Dr. Ytterberg, a clinical rheumatologist and researcher at the Mayo Clinic, Rochester, Minn.

He noted wide disparities in the characteristics of primary vs. secondary osteoarthritis; localized, single-joint disease vs. generalized osteoarthritis; and osteoarthritis associated with osteophyte necrosis, inflammation, or crystal deposition. Dr. Ytterberg compared, for instance, inflammatory, erosive osteoarthritis of the hands with diffuse idiopathic skeletal hyperostosis (DISH).

“Is this all the same disease? I don't know that it makes sense that it is,” he said.

Another major shift is in the way researchers are studying development of osteoarthritis.

“With osteoarthritis, the focus has always been on cartilage. To begin to see frayed cartilage through the arthroscope has always been presumed to be where the action is.”

Microscopic disruption of the extracellular matrix, and later, macroscopic clefts in the cartilage were seen as progressive evidence of encroaching disease.

Now, the focus has shifted, and the target of research is bone. “A large amount of information is now calling attention to what's going on in the chondrocytes: potential changes in cell-signaling pathways,” he said.

Many researchers are now beginning to believe that “subchondral bone is where the problem is,” with cartilage abnormalities perhaps the downstream effect of abnormal wear in response to bone changes, said Dr. Ytterberg.

Others are pursuing the hypothesis that osteoarthritis is an enthesopathy.

These theories, still in their infancy, could one day help characterize a diffusely defined symptom set that may or may not have common origins, he said.

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

FORT LAUDERDALE, FLA. — People with symptomatic osteoarthritis can be differentiated from those with only radiographic evidence of disease using a combination of biomarkers, according to a study presented at the World Congress on Osteoarthritis.

Olga V. Nemirovsky, Ph.D., a researcher at Pfizer Inc. in St. Louis, and her associates, compared a large number of biomarkers of joint matrix protein degradation and synthesis and biomarkers of inflammation using urine, serum, and plasma samples from 83 participants.

Their aim was to identify biomarkers that would indicate any initial efficacy of disease-modifying osteoarthritis drugs for future clinical trials.

Participants included 22 people with symptomatic osteoarthritis; 30 people with only radiographic evidence of disease in their hip and/or knee joints; 19 with only radiographic evidence in their hand and/or spine joints; and 12 controls with no symptoms or radiographic signs of disease.

“We tried to assess each biomarker separately. Then we evaluated combinations of two biomarkers, and then applied multivariate analyses to all biomarkers,” said Dr. Nemirovsky.

Five markers contributed the most to the distinction between symptomatic patients and the others: plasma procollagen type III N-terminal propeptides (PIIINP), prostaglandin PGE2, 15-hydroxyeicosatetraenoic acid (15-HETE), collagen type II neoepitope (TIINE), and procollagen type II N-terminal propeptide (NPII). Although analysis of individual markers revealed significant differences, a combination of markers proved superior to any single assay.

Patients with symptomatic osteoarthritis had significantly higher levels of urinary C-terminal telopeptides of type II collagen (CTX-II), TIINE and collagen type III neoepitope (TIIINE) levels, osteopontin, plasma procollagen type I (PINP), prostaglandin PGE2, 15-HETE, and 3-nitrotyrosine (3-NT) compared with other groups, Dr. Nemirovsky said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

On the other hand, the researchers found significantly lower levels of plasma NPII and urinary aggrecan neoepitope (Agg) in the symptomatic group.

Levels of Agg were higher for the group with radiographic disease in the hip/knee compared with the no-radiographic-evidence group or the symptomatic patients. The researchers used a model to distinguish the patients with radiographic evidence of hip/knee osteoarthritis from the radiographic hand/spine and no-radiographic-evidence groups.

The markers that contributed most to this distinction were Agg, TIINE, PIIINP, PGE2, and 15-HETE.

Gold therapy seems to be a safe treatment option for severe rheumatoid arthritis in both pregnant women and women who are trying to conceive who must discontinue or forgo other teratogenic therapies, according to findings from a small chart review.

The study looked at 14 women with severe rheumatoid arthritis (RA) who became pregnant while taking gold between January 1992 and January 2006. One woman had stopped taking gold therapy 4 weeks prior to conception; four women stayed on gold throughout the pregnancy.

The 14 women reported 20 pregnancies, according to Dr. Mohammed Almarzouqi, a rheumatologist at the University of British Columbia, Vancouver, and his fellow researchers.

Rheumatoid arthritis was considered controlled if there were fewer than four swollen or tender joints in an assessment by a clinic rheumatologist, and if no new prescription of prednisone or nonsteroidal anti-inflammatory drugs was required.

The mean age at pregnancy was 35 years (range 24–41) and the mean disease duration was 8.5 years. Rheumatoid factor was positive in 9 of 14 women.

The amount of time taking gold prior to conception was less than 1 year in seven pregnancies, 1–2 years in four pregnancies, 25–34 months in two pregnancies, and 2–8 years in seven pregnancies. Six of the patients had 11 pregnancies prior to gold therapy.

Ten patients had never taken methotrexate (MTX) prior to conception, while the other four women had discontinued MTX 8–16 months before conception. Thirteen pregnancies had a mean dose of gold while planning pregnancy and prior to conception of 25–50 mg/week. At the high end of the dosage spectrum, two pregnancies followed a dose of 50 mg/every 2 weeks, and in one pregnancy it was 60 mg/week.

At the low end, two pregnancies had a mean dose of 5–10 mg/week, and two other pregnancies had a mean dose of 10 mg every 2 weeks (J. Rheumatol. 2007;34:1827-31).

“In our small series of women taking gold for RA while planning pregnancy, 5 of 20 pregnancies ended in spontaneous abortion,” wrote the investigators.

However, they pointed out that the mean age of women in their study was 35 years, and that the rate of fetal loss in women over 40 and women near that age is higher than for younger women.

Additionally, two of the reported spontaneous abortions occurred in a woman with a “known chromosomal defect.” Two of the women who lost a fetus also reported birth of one healthy baby while taking gold.

The remaining children, including one set of twins, were healthy at birth.

Rheumatoid arthritis flared during just 3 of the 15 full-term pregnancies, and it was controlled in the rest.

Although this study was small, the authors concluded that, in light of the fact that there are so few available disease-modifying antirheumatic drugs that are recommended for pregnant women or women attempting pregnancy, gold is a safe and efficacious rheumatoid arthritis treatment during pregnancy.

The investigators disclosed no conflicts of interest related to this study.

Gold therapy seems to be a safe treatment option for severe rheumatoid arthritis in both pregnant women and women who are trying to conceive who must discontinue or forgo other teratogenic therapies, according to findings from a small chart review.

The study looked at 14 women with severe rheumatoid arthritis (RA) who became pregnant while taking gold between January 1992 and January 2006. One woman had stopped taking gold therapy 4 weeks prior to conception; four women stayed on gold throughout the pregnancy.

The 14 women reported 20 pregnancies, according to Dr. Mohammed Almarzouqi, a rheumatologist at the University of British Columbia, Vancouver, and his fellow researchers.

Rheumatoid arthritis was considered controlled if there were fewer than four swollen or tender joints in an assessment by a clinic rheumatologist, and if no new prescription of prednisone or nonsteroidal anti-inflammatory drugs was required.

The mean age at pregnancy was 35 years (range 24–41) and the mean disease duration was 8.5 years. Rheumatoid factor was positive in 9 of 14 women.

The amount of time taking gold prior to conception was less than 1 year in seven pregnancies, 1–2 years in four pregnancies, 25–34 months in two pregnancies, and 2–8 years in seven pregnancies. Six of the patients had 11 pregnancies prior to gold therapy.

Ten patients had never taken methotrexate (MTX) prior to conception, while the other four women had discontinued MTX 8–16 months before conception. Thirteen pregnancies had a mean dose of gold while planning pregnancy and prior to conception of 25–50 mg/week. At the high end of the dosage spectrum, two pregnancies followed a dose of 50 mg/every 2 weeks, and in one pregnancy it was 60 mg/week.

At the low end, two pregnancies had a mean dose of 5–10 mg/week, and two other pregnancies had a mean dose of 10 mg every 2 weeks (J. Rheumatol. 2007;34:1827-31).

“In our small series of women taking gold for RA while planning pregnancy, 5 of 20 pregnancies ended in spontaneous abortion,” wrote the investigators.

However, they pointed out that the mean age of women in their study was 35 years, and that the rate of fetal loss in women over 40 and women near that age is higher than for younger women.

Additionally, two of the reported spontaneous abortions occurred in a woman with a “known chromosomal defect.” Two of the women who lost a fetus also reported birth of one healthy baby while taking gold.

The remaining children, including one set of twins, were healthy at birth.

Rheumatoid arthritis flared during just 3 of the 15 full-term pregnancies, and it was controlled in the rest.

Although this study was small, the authors concluded that, in light of the fact that there are so few available disease-modifying antirheumatic drugs that are recommended for pregnant women or women attempting pregnancy, gold is a safe and efficacious rheumatoid arthritis treatment during pregnancy.

The investigators disclosed no conflicts of interest related to this study.

Gold therapy seems to be a safe treatment option for severe rheumatoid arthritis in both pregnant women and women who are trying to conceive who must discontinue or forgo other teratogenic therapies, according to findings from a small chart review.

The study looked at 14 women with severe rheumatoid arthritis (RA) who became pregnant while taking gold between January 1992 and January 2006. One woman had stopped taking gold therapy 4 weeks prior to conception; four women stayed on gold throughout the pregnancy.

The 14 women reported 20 pregnancies, according to Dr. Mohammed Almarzouqi, a rheumatologist at the University of British Columbia, Vancouver, and his fellow researchers.

Rheumatoid arthritis was considered controlled if there were fewer than four swollen or tender joints in an assessment by a clinic rheumatologist, and if no new prescription of prednisone or nonsteroidal anti-inflammatory drugs was required.

The mean age at pregnancy was 35 years (range 24–41) and the mean disease duration was 8.5 years. Rheumatoid factor was positive in 9 of 14 women.

The amount of time taking gold prior to conception was less than 1 year in seven pregnancies, 1–2 years in four pregnancies, 25–34 months in two pregnancies, and 2–8 years in seven pregnancies. Six of the patients had 11 pregnancies prior to gold therapy.

Ten patients had never taken methotrexate (MTX) prior to conception, while the other four women had discontinued MTX 8–16 months before conception. Thirteen pregnancies had a mean dose of gold while planning pregnancy and prior to conception of 25–50 mg/week. At the high end of the dosage spectrum, two pregnancies followed a dose of 50 mg/every 2 weeks, and in one pregnancy it was 60 mg/week.

At the low end, two pregnancies had a mean dose of 5–10 mg/week, and two other pregnancies had a mean dose of 10 mg every 2 weeks (J. Rheumatol. 2007;34:1827-31).

“In our small series of women taking gold for RA while planning pregnancy, 5 of 20 pregnancies ended in spontaneous abortion,” wrote the investigators.

However, they pointed out that the mean age of women in their study was 35 years, and that the rate of fetal loss in women over 40 and women near that age is higher than for younger women.

Additionally, two of the reported spontaneous abortions occurred in a woman with a “known chromosomal defect.” Two of the women who lost a fetus also reported birth of one healthy baby while taking gold.

The remaining children, including one set of twins, were healthy at birth.

Rheumatoid arthritis flared during just 3 of the 15 full-term pregnancies, and it was controlled in the rest.

Although this study was small, the authors concluded that, in light of the fact that there are so few available disease-modifying antirheumatic drugs that are recommended for pregnant women or women attempting pregnancy, gold is a safe and efficacious rheumatoid arthritis treatment during pregnancy.

The investigators disclosed no conflicts of interest related to this study.

BOSTON — Overweight patients with early rheumatoid arthritis were less likely to achieve remission with conventional disease-modifying drugs than patients with a normal body mass index.

Overweight and obese patients fared better if they were treated with a regimen that also included infliximab, Dr. Marjatta Leirisalo-Repo said at the annual meeting of the American College of Rheumatology.

The study enrolled 100 patients with RA of less than 1 year's duration from 15 centers, and randomized them to methotrexate, sulfasalazine, hydroxychloroquine, and prednisone plus either infliximab or placebo for 6 months.

Patients' mean age was 46 years, median duration of symptoms was 4 months, mean number of swollen joints was 15, and mean number of tender joints was 20. All participants had morning stiffness lasting 45 minutes or more.

At baseline, the mean erythrocyte sedimentation rate (ESR) was 33 mm/h and the mean Health Assessment Questionnaire (HAQ) score was 1.

In all, 67% of patients were female and 68% were rheumatoid factor positive. None of the patients had previously been treated with a disease-modifying antirheumatic drug (DMARD).

The DMARD regimens were individually tailored, with maximum dosages of methotrexate of 25 mg/week and maximum dosages of sulfasalazine of 2 g/day. Hydroxychloroquine was given in dosages of 35 mg/kg per week and prednisone in 7.5 mg/day. Patients randomized to also receive infliximab received it in dosages of 3 mg/kg at weeks 4, 6, 10, 18, and 26.

Remission was defined as early-morning stiffness lasting less than 15 minutes; no fatigue, joint pain, or swollen or tender joints; and an ESR less than 30 mm/hour.

At 6 months, 53% of patients had achieved remission, said Dr. Leirisalo-Repo, professor of rheumatology at Helsinki University Central Hospital and the University of Helsinki.

The percentages of patients in remission at 6 months in the infliximab and placebo groups were 58% and 47%, respectively. At 12 months, the corresponding percentages were 58% and 52%.

At 6 months, 63% of placebo patients whose body mass index (BMI) was less than 25 kg/m

“No such association was seen in the infliximab-treated patients,” Dr. Leirisalo-Repo said. Remission rates in the normal, overweight, and obese groups receiving the biologic agent at 6 months were 55%, 68%, and 46%, respectively.

At 12 months, the remission rates for normal, overweight, and obese patients in the placebo group were 58%, 35%, and 25%, whereas those in the infliximab group were 45%, 74%, and 55%.

It appears obesity is associated with a lack of response to conventional DMARDs, even when these drugs are given in combination, but infliximab was able to overcome this DMARD resistance, Dr. Leirisalo-Repo said. “Fat is proinflammatory, and obesity is characterized by systemic inflammation,” she said in a press conference.

Dr. Leirisalo-Repo disclosed that she has received research grants from Schering-Plough Oy in Finland.

BOSTON — Overweight patients with early rheumatoid arthritis were less likely to achieve remission with conventional disease-modifying drugs than patients with a normal body mass index.

Overweight and obese patients fared better if they were treated with a regimen that also included infliximab, Dr. Marjatta Leirisalo-Repo said at the annual meeting of the American College of Rheumatology.

The study enrolled 100 patients with RA of less than 1 year's duration from 15 centers, and randomized them to methotrexate, sulfasalazine, hydroxychloroquine, and prednisone plus either infliximab or placebo for 6 months.

Patients' mean age was 46 years, median duration of symptoms was 4 months, mean number of swollen joints was 15, and mean number of tender joints was 20. All participants had morning stiffness lasting 45 minutes or more.

At baseline, the mean erythrocyte sedimentation rate (ESR) was 33 mm/h and the mean Health Assessment Questionnaire (HAQ) score was 1.

In all, 67% of patients were female and 68% were rheumatoid factor positive. None of the patients had previously been treated with a disease-modifying antirheumatic drug (DMARD).

The DMARD regimens were individually tailored, with maximum dosages of methotrexate of 25 mg/week and maximum dosages of sulfasalazine of 2 g/day. Hydroxychloroquine was given in dosages of 35 mg/kg per week and prednisone in 7.5 mg/day. Patients randomized to also receive infliximab received it in dosages of 3 mg/kg at weeks 4, 6, 10, 18, and 26.

Remission was defined as early-morning stiffness lasting less than 15 minutes; no fatigue, joint pain, or swollen or tender joints; and an ESR less than 30 mm/hour.

At 6 months, 53% of patients had achieved remission, said Dr. Leirisalo-Repo, professor of rheumatology at Helsinki University Central Hospital and the University of Helsinki.

The percentages of patients in remission at 6 months in the infliximab and placebo groups were 58% and 47%, respectively. At 12 months, the corresponding percentages were 58% and 52%.

At 6 months, 63% of placebo patients whose body mass index (BMI) was less than 25 kg/m

“No such association was seen in the infliximab-treated patients,” Dr. Leirisalo-Repo said. Remission rates in the normal, overweight, and obese groups receiving the biologic agent at 6 months were 55%, 68%, and 46%, respectively.

At 12 months, the remission rates for normal, overweight, and obese patients in the placebo group were 58%, 35%, and 25%, whereas those in the infliximab group were 45%, 74%, and 55%.

It appears obesity is associated with a lack of response to conventional DMARDs, even when these drugs are given in combination, but infliximab was able to overcome this DMARD resistance, Dr. Leirisalo-Repo said. “Fat is proinflammatory, and obesity is characterized by systemic inflammation,” she said in a press conference.

Dr. Leirisalo-Repo disclosed that she has received research grants from Schering-Plough Oy in Finland.

BOSTON — Overweight patients with early rheumatoid arthritis were less likely to achieve remission with conventional disease-modifying drugs than patients with a normal body mass index.

Overweight and obese patients fared better if they were treated with a regimen that also included infliximab, Dr. Marjatta Leirisalo-Repo said at the annual meeting of the American College of Rheumatology.

The study enrolled 100 patients with RA of less than 1 year's duration from 15 centers, and randomized them to methotrexate, sulfasalazine, hydroxychloroquine, and prednisone plus either infliximab or placebo for 6 months.

Patients' mean age was 46 years, median duration of symptoms was 4 months, mean number of swollen joints was 15, and mean number of tender joints was 20. All participants had morning stiffness lasting 45 minutes or more.

At baseline, the mean erythrocyte sedimentation rate (ESR) was 33 mm/h and the mean Health Assessment Questionnaire (HAQ) score was 1.

In all, 67% of patients were female and 68% were rheumatoid factor positive. None of the patients had previously been treated with a disease-modifying antirheumatic drug (DMARD).

The DMARD regimens were individually tailored, with maximum dosages of methotrexate of 25 mg/week and maximum dosages of sulfasalazine of 2 g/day. Hydroxychloroquine was given in dosages of 35 mg/kg per week and prednisone in 7.5 mg/day. Patients randomized to also receive infliximab received it in dosages of 3 mg/kg at weeks 4, 6, 10, 18, and 26.

Remission was defined as early-morning stiffness lasting less than 15 minutes; no fatigue, joint pain, or swollen or tender joints; and an ESR less than 30 mm/hour.

At 6 months, 53% of patients had achieved remission, said Dr. Leirisalo-Repo, professor of rheumatology at Helsinki University Central Hospital and the University of Helsinki.

The percentages of patients in remission at 6 months in the infliximab and placebo groups were 58% and 47%, respectively. At 12 months, the corresponding percentages were 58% and 52%.

At 6 months, 63% of placebo patients whose body mass index (BMI) was less than 25 kg/m

“No such association was seen in the infliximab-treated patients,” Dr. Leirisalo-Repo said. Remission rates in the normal, overweight, and obese groups receiving the biologic agent at 6 months were 55%, 68%, and 46%, respectively.

At 12 months, the remission rates for normal, overweight, and obese patients in the placebo group were 58%, 35%, and 25%, whereas those in the infliximab group were 45%, 74%, and 55%.

It appears obesity is associated with a lack of response to conventional DMARDs, even when these drugs are given in combination, but infliximab was able to overcome this DMARD resistance, Dr. Leirisalo-Repo said. “Fat is proinflammatory, and obesity is characterized by systemic inflammation,” she said in a press conference.

Dr. Leirisalo-Repo disclosed that she has received research grants from Schering-Plough Oy in Finland.

SAN FRANCISCO — Cognitive-behavioral therapy for comorbid insomnia in patients with osteoarthritis not only improved sleep but also reduced self-reported pain in a randomized, controlled pilot study of 51 patients.

The improvements in both sleep and pain levels persisted at 1-year follow-up. This is the first study to demonstrate such a duration of benefit from cognitive-behavioral therapy for insomnia in patients with comorbid chronic medical illness of any kind, reported Michael V. Vitiello, Ph.D, and his associates in a poster presentation at the annual meeting of the Gerontological Society of America.

This preliminary study suggests that improving sleep can be “analgesic” in patients with osteoarthritis, said Dr. Vitiello, professor of psychiatry and behavioral sciences at the University of Washington, Seattle. “Techniques to improve sleep should be considered for addition to treatment programs for pain management in osteoarthritis and possibly other pain states,” he added.

More than half of older adults develop osteoarthritis, and a majority of these develop significant sleep disturbance. The pain initiates and exacerbates the sleep disturbance, and the disturbed sleep then seems to maintain and exacerbate pain by lowering pain thresholds and amplifying transmission of pain signals, he said.

The study randomized 23 patients (18 women and 5 men) to cognitive-behavioral therapy for insomnia and 28 patients (27 women, 1 man) to a control group that received an intervention focused on attention control, stress management, and wellness. Neither group specifically addressed pain control. Each group met 2 hours per week for 8 weeks for the intervention.

Several measures of insomnia improved significantly in the treatment group but not in controls. Sleep latency (the time it takes to fall asleep) decreased from a mean of 40 minutes to 24 minutes, and nighttime wakefulness decreased from 62 to 25 minutes. Sleep efficiency (the proportion of time in bed spent asleep) improved from 71% to 84%.

Self-reported pain on the Short Form-36 pain scale improved from a score of 56 before cognitive-behavioral therapy to 66 afterward (higher scores indicate less pain), but did not change significantly in the control group. There was a nonsignificant trend toward reduced pain in the treatment group as assessed by the McGill Pain Questionnaire.

After posttreatment results were assessed, 10 patients in the control group crossed over to receive cognitive-behavioral therapy for insomnia. Results of 1-year follow-up in 19 patients from the original cognitive-behavioral therapy group plus the 10 crossovers were nearly identical to the results of the after-treatment assessments, showing duration of the improvements over time, Dr. Vitiello said.

Cognitive-behavioral therapy for insomnia is “not the kind of thing that a physician can do in an office visit, but it can be done by trained health care professionals in relatively quick fashion in group settings,” he said. The cognitive-behavioral intervention consisted of a fairly standard series of behavioral manipulations such as sleep restriction (teaching patients to somewhat curtail their time in bed), stimulus control (telling them not to go to bed unless sleepy), sleep hygiene (teaching them how to nap appropriately), and other techniques.

“We always think of sleep disturbance as a symptom, as secondary,” Dr. Vitiello said. “What we're learning, really, is that sleep is interactive with illness, and it is not simply a symptom.”

SAN FRANCISCO — Cognitive-behavioral therapy for comorbid insomnia in patients with osteoarthritis not only improved sleep but also reduced self-reported pain in a randomized, controlled pilot study of 51 patients.

The improvements in both sleep and pain levels persisted at 1-year follow-up. This is the first study to demonstrate such a duration of benefit from cognitive-behavioral therapy for insomnia in patients with comorbid chronic medical illness of any kind, reported Michael V. Vitiello, Ph.D, and his associates in a poster presentation at the annual meeting of the Gerontological Society of America.

This preliminary study suggests that improving sleep can be “analgesic” in patients with osteoarthritis, said Dr. Vitiello, professor of psychiatry and behavioral sciences at the University of Washington, Seattle. “Techniques to improve sleep should be considered for addition to treatment programs for pain management in osteoarthritis and possibly other pain states,” he added.

More than half of older adults develop osteoarthritis, and a majority of these develop significant sleep disturbance. The pain initiates and exacerbates the sleep disturbance, and the disturbed sleep then seems to maintain and exacerbate pain by lowering pain thresholds and amplifying transmission of pain signals, he said.

The study randomized 23 patients (18 women and 5 men) to cognitive-behavioral therapy for insomnia and 28 patients (27 women, 1 man) to a control group that received an intervention focused on attention control, stress management, and wellness. Neither group specifically addressed pain control. Each group met 2 hours per week for 8 weeks for the intervention.

Several measures of insomnia improved significantly in the treatment group but not in controls. Sleep latency (the time it takes to fall asleep) decreased from a mean of 40 minutes to 24 minutes, and nighttime wakefulness decreased from 62 to 25 minutes. Sleep efficiency (the proportion of time in bed spent asleep) improved from 71% to 84%.

Self-reported pain on the Short Form-36 pain scale improved from a score of 56 before cognitive-behavioral therapy to 66 afterward (higher scores indicate less pain), but did not change significantly in the control group. There was a nonsignificant trend toward reduced pain in the treatment group as assessed by the McGill Pain Questionnaire.

After posttreatment results were assessed, 10 patients in the control group crossed over to receive cognitive-behavioral therapy for insomnia. Results of 1-year follow-up in 19 patients from the original cognitive-behavioral therapy group plus the 10 crossovers were nearly identical to the results of the after-treatment assessments, showing duration of the improvements over time, Dr. Vitiello said.

Cognitive-behavioral therapy for insomnia is “not the kind of thing that a physician can do in an office visit, but it can be done by trained health care professionals in relatively quick fashion in group settings,” he said. The cognitive-behavioral intervention consisted of a fairly standard series of behavioral manipulations such as sleep restriction (teaching patients to somewhat curtail their time in bed), stimulus control (telling them not to go to bed unless sleepy), sleep hygiene (teaching them how to nap appropriately), and other techniques.

“We always think of sleep disturbance as a symptom, as secondary,” Dr. Vitiello said. “What we're learning, really, is that sleep is interactive with illness, and it is not simply a symptom.”

SAN FRANCISCO — Cognitive-behavioral therapy for comorbid insomnia in patients with osteoarthritis not only improved sleep but also reduced self-reported pain in a randomized, controlled pilot study of 51 patients.

The improvements in both sleep and pain levels persisted at 1-year follow-up. This is the first study to demonstrate such a duration of benefit from cognitive-behavioral therapy for insomnia in patients with comorbid chronic medical illness of any kind, reported Michael V. Vitiello, Ph.D, and his associates in a poster presentation at the annual meeting of the Gerontological Society of America.

This preliminary study suggests that improving sleep can be “analgesic” in patients with osteoarthritis, said Dr. Vitiello, professor of psychiatry and behavioral sciences at the University of Washington, Seattle. “Techniques to improve sleep should be considered for addition to treatment programs for pain management in osteoarthritis and possibly other pain states,” he added.

More than half of older adults develop osteoarthritis, and a majority of these develop significant sleep disturbance. The pain initiates and exacerbates the sleep disturbance, and the disturbed sleep then seems to maintain and exacerbate pain by lowering pain thresholds and amplifying transmission of pain signals, he said.

The study randomized 23 patients (18 women and 5 men) to cognitive-behavioral therapy for insomnia and 28 patients (27 women, 1 man) to a control group that received an intervention focused on attention control, stress management, and wellness. Neither group specifically addressed pain control. Each group met 2 hours per week for 8 weeks for the intervention.

Several measures of insomnia improved significantly in the treatment group but not in controls. Sleep latency (the time it takes to fall asleep) decreased from a mean of 40 minutes to 24 minutes, and nighttime wakefulness decreased from 62 to 25 minutes. Sleep efficiency (the proportion of time in bed spent asleep) improved from 71% to 84%.

Self-reported pain on the Short Form-36 pain scale improved from a score of 56 before cognitive-behavioral therapy to 66 afterward (higher scores indicate less pain), but did not change significantly in the control group. There was a nonsignificant trend toward reduced pain in the treatment group as assessed by the McGill Pain Questionnaire.

After posttreatment results were assessed, 10 patients in the control group crossed over to receive cognitive-behavioral therapy for insomnia. Results of 1-year follow-up in 19 patients from the original cognitive-behavioral therapy group plus the 10 crossovers were nearly identical to the results of the after-treatment assessments, showing duration of the improvements over time, Dr. Vitiello said.

Cognitive-behavioral therapy for insomnia is “not the kind of thing that a physician can do in an office visit, but it can be done by trained health care professionals in relatively quick fashion in group settings,” he said. The cognitive-behavioral intervention consisted of a fairly standard series of behavioral manipulations such as sleep restriction (teaching patients to somewhat curtail their time in bed), stimulus control (telling them not to go to bed unless sleepy), sleep hygiene (teaching them how to nap appropriately), and other techniques.

“We always think of sleep disturbance as a symptom, as secondary,” Dr. Vitiello said. “What we're learning, really, is that sleep is interactive with illness, and it is not simply a symptom.”

BOSTON — Preventing meniscal damage should be a top therapeutic priority in the fight against knee osteoarthritis, Dr. Martin Englund said at the annual meeting of the American College of Rheumatology.

The Multicenter Osteoarthritis study (MOST) demonstrated for the first time that meniscal damage without surgical resection is a risk factor for tibiofemoral radiographic knee osteoarthritis.

The onset of knee osteoarthritis (OA) after the surgical removal of all or part of a torn meniscus is common, and numerous longitudinal studies have identified meniscectomy as a significant risk factor for knee OA, according to Dr. Englund, of Boston University, and his colleagues. However, no studies have demonstrated that meniscal damage without surgical resection is associated with the development of incident radiographic knee OA (ROA), he said. To evaluate the effect of baseline meniscal damage on incident tibiofemoral radiographic OA, the researchers conducted a nested case-control investigation comprising patients enrolled in the MOST study, a prospective observational study of 3,026 individuals older than age 50 who have or are at high risk for knee OA. Prior knee surgery patients were excluded. Participants had standardized, weight-bearing fixed-flexion x-rays at baseline and at 30 months.

These x-rays were read paired by a musculoskeletal radiologist and rheumatologist, both blinded to clinical and MRI data, Dr. Englund explained.

For the current study, 52 knees with no tibiofemoral ROA at baseline but evidence of grade 2 or higher ROA on the Kellgren-Lawrence scale in the 30-month follow-up were cases; 130 knees drawn from the same source population but with no tibiofemoral ROA at follow-up were controls.

To assess the baseline meniscal status of the knees, two blinded musculoskeletal radiologists reviewed coronal and sagittal fast spin echo MRI images and evaluated each on a collapsed scale. Knees with no damage were grade 0, those with a minor tear were grade 1, and those with a nondisplaced tear, displaced tear, maceration, or destruction were considered grade 2.

The investigators analyzed the link between meniscal damage and ROA using two logistic regression models (one in which the meniscal score was entered as 0, 1, or 2, and one in which it was entered as meniscal damage or no damage) adjusted for age, sex, body mass index, physical activity, and mechanical knee alignment.

“Meniscal damage at baseline was significantly more common in cases than in controls,” Dr. Englund reported, evident in 52% of case knees, versus 18% of controls.

In a multivariable model, the odds ratio of incident tibiofemoral ROA increased as the meniscal score increased, Dr. Englund noted. When knees with meniscal damage were compared with knees that had a normal meniscus at baseline, the adjusted odds ratio for ROA at 30 months was 4.3 for knees with a meniscal score of 1 and 7.8 for those with a meniscal score of 2.

Dr. Englund disclosed no financial conflicts related to his presentation.

Meniscal damage at baseline was 52% more common in case knees versus 18% of controls. DR. ENGLUND

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Preventing meniscal damage should be a top therapeutic priority in the fight against knee osteoarthritis, Dr. Martin Englund said at the annual meeting of the American College of Rheumatology.

The Multicenter Osteoarthritis study (MOST) demonstrated for the first time that meniscal damage without surgical resection is a risk factor for tibiofemoral radiographic knee osteoarthritis.

The onset of knee osteoarthritis (OA) after the surgical removal of all or part of a torn meniscus is common, and numerous longitudinal studies have identified meniscectomy as a significant risk factor for knee OA, according to Dr. Englund, of Boston University, and his colleagues. However, no studies have demonstrated that meniscal damage without surgical resection is associated with the development of incident radiographic knee OA (ROA), he said. To evaluate the effect of baseline meniscal damage on incident tibiofemoral radiographic OA, the researchers conducted a nested case-control investigation comprising patients enrolled in the MOST study, a prospective observational study of 3,026 individuals older than age 50 who have or are at high risk for knee OA. Prior knee surgery patients were excluded. Participants had standardized, weight-bearing fixed-flexion x-rays at baseline and at 30 months.

These x-rays were read paired by a musculoskeletal radiologist and rheumatologist, both blinded to clinical and MRI data, Dr. Englund explained.

For the current study, 52 knees with no tibiofemoral ROA at baseline but evidence of grade 2 or higher ROA on the Kellgren-Lawrence scale in the 30-month follow-up were cases; 130 knees drawn from the same source population but with no tibiofemoral ROA at follow-up were controls.

To assess the baseline meniscal status of the knees, two blinded musculoskeletal radiologists reviewed coronal and sagittal fast spin echo MRI images and evaluated each on a collapsed scale. Knees with no damage were grade 0, those with a minor tear were grade 1, and those with a nondisplaced tear, displaced tear, maceration, or destruction were considered grade 2.

The investigators analyzed the link between meniscal damage and ROA using two logistic regression models (one in which the meniscal score was entered as 0, 1, or 2, and one in which it was entered as meniscal damage or no damage) adjusted for age, sex, body mass index, physical activity, and mechanical knee alignment.

“Meniscal damage at baseline was significantly more common in cases than in controls,” Dr. Englund reported, evident in 52% of case knees, versus 18% of controls.

In a multivariable model, the odds ratio of incident tibiofemoral ROA increased as the meniscal score increased, Dr. Englund noted. When knees with meniscal damage were compared with knees that had a normal meniscus at baseline, the adjusted odds ratio for ROA at 30 months was 4.3 for knees with a meniscal score of 1 and 7.8 for those with a meniscal score of 2.

Dr. Englund disclosed no financial conflicts related to his presentation.

Meniscal damage at baseline was 52% more common in case knees versus 18% of controls. DR. ENGLUND

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Preventing meniscal damage should be a top therapeutic priority in the fight against knee osteoarthritis, Dr. Martin Englund said at the annual meeting of the American College of Rheumatology.

The Multicenter Osteoarthritis study (MOST) demonstrated for the first time that meniscal damage without surgical resection is a risk factor for tibiofemoral radiographic knee osteoarthritis.

The onset of knee osteoarthritis (OA) after the surgical removal of all or part of a torn meniscus is common, and numerous longitudinal studies have identified meniscectomy as a significant risk factor for knee OA, according to Dr. Englund, of Boston University, and his colleagues. However, no studies have demonstrated that meniscal damage without surgical resection is associated with the development of incident radiographic knee OA (ROA), he said. To evaluate the effect of baseline meniscal damage on incident tibiofemoral radiographic OA, the researchers conducted a nested case-control investigation comprising patients enrolled in the MOST study, a prospective observational study of 3,026 individuals older than age 50 who have or are at high risk for knee OA. Prior knee surgery patients were excluded. Participants had standardized, weight-bearing fixed-flexion x-rays at baseline and at 30 months.

These x-rays were read paired by a musculoskeletal radiologist and rheumatologist, both blinded to clinical and MRI data, Dr. Englund explained.

For the current study, 52 knees with no tibiofemoral ROA at baseline but evidence of grade 2 or higher ROA on the Kellgren-Lawrence scale in the 30-month follow-up were cases; 130 knees drawn from the same source population but with no tibiofemoral ROA at follow-up were controls.

To assess the baseline meniscal status of the knees, two blinded musculoskeletal radiologists reviewed coronal and sagittal fast spin echo MRI images and evaluated each on a collapsed scale. Knees with no damage were grade 0, those with a minor tear were grade 1, and those with a nondisplaced tear, displaced tear, maceration, or destruction were considered grade 2.

The investigators analyzed the link between meniscal damage and ROA using two logistic regression models (one in which the meniscal score was entered as 0, 1, or 2, and one in which it was entered as meniscal damage or no damage) adjusted for age, sex, body mass index, physical activity, and mechanical knee alignment.

“Meniscal damage at baseline was significantly more common in cases than in controls,” Dr. Englund reported, evident in 52% of case knees, versus 18% of controls.

In a multivariable model, the odds ratio of incident tibiofemoral ROA increased as the meniscal score increased, Dr. Englund noted. When knees with meniscal damage were compared with knees that had a normal meniscus at baseline, the adjusted odds ratio for ROA at 30 months was 4.3 for knees with a meniscal score of 1 and 7.8 for those with a meniscal score of 2.

Dr. Englund disclosed no financial conflicts related to his presentation.

Meniscal damage at baseline was 52% more common in case knees versus 18% of controls. DR. ENGLUND

ELSEVIER GLOBAL MEDICAL NEWS

In a reversal, the Drug Enforcement Administration will now allow physicians to write up to three prescriptions for a 90-day supply of schedule II controlled substances.

The final rule, published in November, is viewed as a victory by pain medicine specialists, said Dr. B. Todd Sitzman, American Academy of Pain Medicine president and director of advanced pain therapy at the Forrest General Hospital's cancer center in Hattiesburg, Miss.

“It's an indication that [DEA officials] have listened to pain physicians and to the pain patient community,” he said in an interview.

The rule overturns an interim policy that prohibited the dispensing of multiple prescriptions at a single office visit and clarifies the DEA's expectations, said Dr. Sitzman.

Under the new policy, physicians may write prescriptions labeled “do not fill until,” with a preset date. This means patients can get a new prescription every 30 days, for 3 months, without having to return to the physician's office.

The prescriptions do not qualify as refills. They still must be taken to a pharmacy to be filled. DEA also said that the 90-day limit is the maximum according to its interpretation of congressional intent and the statute covering schedule II controlled substances.

In the rule, the DEA addressed several areas of concern to prescribing physicians.

The agency said it “wishes to dispel the mistaken notion among a small number of medical professionals that the agency has embarked on a campaign to 'target' physicians who prescribe controlled substances for the treatment of pain (or that physicians must curb their legitimate prescribing of pain medications to avoid legal liability).”

The agency noted that in any given year, fewer than 1 in 10,000 physicians lose their controlled substance registration because of a DEA investigation.

But, added the agency, the rule does not alter longstanding state and federal requirements that controlled substances can only be prescribed, administered or dispensed for a legitimate medical purpose by a physician acting in the usual course of professional practice.

The changes were first proposed in 2006, when the DEA was asked by commenters to issue specific guidance on how a clinician could assess pain, when a physician should prescribe an opioid, or how to use opioids.

But the agency said it would not do so, noting it does not regulate the practice of medicine and these topics are better addressed by professional organizations, medical schools, and postgraduate medical training.

Dr. Sitzman said the lack of strict guidelines is a positive thing.

Other organizations were also heartened by the rule change. In a statement, Dr. Rebecca Patchin, an American Medical Association board member, said the change “will give patients better access to the prescription drugs they need and continue to minimize the risks controlled substances pose to public health and safety.”

In a reversal, the Drug Enforcement Administration will now allow physicians to write up to three prescriptions for a 90-day supply of schedule II controlled substances.

The final rule, published in November, is viewed as a victory by pain medicine specialists, said Dr. B. Todd Sitzman, American Academy of Pain Medicine president and director of advanced pain therapy at the Forrest General Hospital's cancer center in Hattiesburg, Miss.

“It's an indication that [DEA officials] have listened to pain physicians and to the pain patient community,” he said in an interview.

The rule overturns an interim policy that prohibited the dispensing of multiple prescriptions at a single office visit and clarifies the DEA's expectations, said Dr. Sitzman.

Under the new policy, physicians may write prescriptions labeled “do not fill until,” with a preset date. This means patients can get a new prescription every 30 days, for 3 months, without having to return to the physician's office.

The prescriptions do not qualify as refills. They still must be taken to a pharmacy to be filled. DEA also said that the 90-day limit is the maximum according to its interpretation of congressional intent and the statute covering schedule II controlled substances.

In the rule, the DEA addressed several areas of concern to prescribing physicians.

The agency said it “wishes to dispel the mistaken notion among a small number of medical professionals that the agency has embarked on a campaign to 'target' physicians who prescribe controlled substances for the treatment of pain (or that physicians must curb their legitimate prescribing of pain medications to avoid legal liability).”

The agency noted that in any given year, fewer than 1 in 10,000 physicians lose their controlled substance registration because of a DEA investigation.

But, added the agency, the rule does not alter longstanding state and federal requirements that controlled substances can only be prescribed, administered or dispensed for a legitimate medical purpose by a physician acting in the usual course of professional practice.

The changes were first proposed in 2006, when the DEA was asked by commenters to issue specific guidance on how a clinician could assess pain, when a physician should prescribe an opioid, or how to use opioids.

But the agency said it would not do so, noting it does not regulate the practice of medicine and these topics are better addressed by professional organizations, medical schools, and postgraduate medical training.

Dr. Sitzman said the lack of strict guidelines is a positive thing.

Other organizations were also heartened by the rule change. In a statement, Dr. Rebecca Patchin, an American Medical Association board member, said the change “will give patients better access to the prescription drugs they need and continue to minimize the risks controlled substances pose to public health and safety.”

In a reversal, the Drug Enforcement Administration will now allow physicians to write up to three prescriptions for a 90-day supply of schedule II controlled substances.

The final rule, published in November, is viewed as a victory by pain medicine specialists, said Dr. B. Todd Sitzman, American Academy of Pain Medicine president and director of advanced pain therapy at the Forrest General Hospital's cancer center in Hattiesburg, Miss.

“It's an indication that [DEA officials] have listened to pain physicians and to the pain patient community,” he said in an interview.

The rule overturns an interim policy that prohibited the dispensing of multiple prescriptions at a single office visit and clarifies the DEA's expectations, said Dr. Sitzman.

Under the new policy, physicians may write prescriptions labeled “do not fill until,” with a preset date. This means patients can get a new prescription every 30 days, for 3 months, without having to return to the physician's office.

The prescriptions do not qualify as refills. They still must be taken to a pharmacy to be filled. DEA also said that the 90-day limit is the maximum according to its interpretation of congressional intent and the statute covering schedule II controlled substances.

In the rule, the DEA addressed several areas of concern to prescribing physicians.

The agency said it “wishes to dispel the mistaken notion among a small number of medical professionals that the agency has embarked on a campaign to 'target' physicians who prescribe controlled substances for the treatment of pain (or that physicians must curb their legitimate prescribing of pain medications to avoid legal liability).”

The agency noted that in any given year, fewer than 1 in 10,000 physicians lose their controlled substance registration because of a DEA investigation.

But, added the agency, the rule does not alter longstanding state and federal requirements that controlled substances can only be prescribed, administered or dispensed for a legitimate medical purpose by a physician acting in the usual course of professional practice.

The changes were first proposed in 2006, when the DEA was asked by commenters to issue specific guidance on how a clinician could assess pain, when a physician should prescribe an opioid, or how to use opioids.

But the agency said it would not do so, noting it does not regulate the practice of medicine and these topics are better addressed by professional organizations, medical schools, and postgraduate medical training.

Dr. Sitzman said the lack of strict guidelines is a positive thing.

Other organizations were also heartened by the rule change. In a statement, Dr. Rebecca Patchin, an American Medical Association board member, said the change “will give patients better access to the prescription drugs they need and continue to minimize the risks controlled substances pose to public health and safety.”

BOSTON — A single course of the humanized anti-CD20 antibody ocrelizumab was safe and effective for rheumatoid arthritis in a phase I/II trial, Dr. Mark Genovese reported at the annual meeting of the American College of Rheumatology.

Ocrelizumab is similar to the chimeric anti-CD20 antibody rituximab in its ability to deplete B cells, but this second-generation antibody differs in its Fc region by two amino acid sequences, resulting in slightly increased antibody-dependent cytotoxicity and slightly decreased complement-dependent toxicity, Dr. Genovese said.

The trial included 237 rheumatoid arthritis (RA) patients who had an inadequate response to methotrexate and received a single course of ocrelizumab in doses of 10 mg, 50 mg, 200 mg, 500 mg, or 1000 mg or placebo, given by intravenous infusion on days 1 and 15. There was no treatment with corticosteroids before the infusions, and patients remained on a stable 10- to 25-mg/week dose of methotrexate through 72 weeks.

Clinical assessments were done every 4 weeks until week 24, at which time efficacy was evaluated, and every 12 weeks thereafter.

Most patients were women in their 50s, all were rheumatoid factor positive, and their mean disease duration exceeded 10 years. At baseline, patients had moderate to severe RA and had failed on average at least two disease modifying drugs. Slightly fewer than half had tried and failed with a tumor necrosis factor blocker, said Dr. Genovese, a rheumatologist at Stanford (Calif.) University.

Rapid depletion of B cells was seen in patients in all active treatment groups after the infusions, followed by a gradual dose-dependent repletion. Higher doses demonstrated the greatest efficacy at week 24, with ACR50 responses seen among 25%, 20%, and 28% of patients in the 200-, 500-, and 1,000-mg groups. Remission was achieved by 10%, 3%, and 8% of patients in these groups, respectively. Among placebo patients, ACR50 responses and remission were achieved by 7% and 2%, respectively.

The higher doses also showed greater reductions in C-reactive protein and low immunogenicity, he said.

The most frequent adverse events were infusion related, including headaches, nausea, chills, pyrexia, and dizziness. These events were similar across the active treatment groups and occurred more frequently than in the placebo group.

Rates of serious adverse events were similar across all groups, with 15 events being seen in the placebo group and 14, 20, 18, 23, and 15 events in the 10-, 50-, 200-, 500-, and 1,000-mg groups, respectively.

There was one metastatic ovarian cancer in the placebo group, two basal cell carcinomas in a single patient at the 10-mg dose, one laryngeal cancer and one breast cancer in the 50-mg group, one B-cell lymphoma in the 200-mg group, and one adenocarcinoma and two basal cell carcinomas in the 500-mg group. No malignancies were seen in the highest dose group.

Administration of ocrelizumab was tied to a slight decrease in immunoglobulin M levels, but this did not appear to have any clinical significance, since there were no infections associated with this decrease, he said.

Dr. Genovese disclosed financial ties to trial funder Genentech Inc. as well as Biogen Idec Inc., and Hoffmann-LaRoche Ltd.

BOSTON — A single course of the humanized anti-CD20 antibody ocrelizumab was safe and effective for rheumatoid arthritis in a phase I/II trial, Dr. Mark Genovese reported at the annual meeting of the American College of Rheumatology.

Ocrelizumab is similar to the chimeric anti-CD20 antibody rituximab in its ability to deplete B cells, but this second-generation antibody differs in its Fc region by two amino acid sequences, resulting in slightly increased antibody-dependent cytotoxicity and slightly decreased complement-dependent toxicity, Dr. Genovese said.

The trial included 237 rheumatoid arthritis (RA) patients who had an inadequate response to methotrexate and received a single course of ocrelizumab in doses of 10 mg, 50 mg, 200 mg, 500 mg, or 1000 mg or placebo, given by intravenous infusion on days 1 and 15. There was no treatment with corticosteroids before the infusions, and patients remained on a stable 10- to 25-mg/week dose of methotrexate through 72 weeks.

Clinical assessments were done every 4 weeks until week 24, at which time efficacy was evaluated, and every 12 weeks thereafter.

Most patients were women in their 50s, all were rheumatoid factor positive, and their mean disease duration exceeded 10 years. At baseline, patients had moderate to severe RA and had failed on average at least two disease modifying drugs. Slightly fewer than half had tried and failed with a tumor necrosis factor blocker, said Dr. Genovese, a rheumatologist at Stanford (Calif.) University.

Rapid depletion of B cells was seen in patients in all active treatment groups after the infusions, followed by a gradual dose-dependent repletion. Higher doses demonstrated the greatest efficacy at week 24, with ACR50 responses seen among 25%, 20%, and 28% of patients in the 200-, 500-, and 1,000-mg groups. Remission was achieved by 10%, 3%, and 8% of patients in these groups, respectively. Among placebo patients, ACR50 responses and remission were achieved by 7% and 2%, respectively.

The higher doses also showed greater reductions in C-reactive protein and low immunogenicity, he said.

The most frequent adverse events were infusion related, including headaches, nausea, chills, pyrexia, and dizziness. These events were similar across the active treatment groups and occurred more frequently than in the placebo group.

Rates of serious adverse events were similar across all groups, with 15 events being seen in the placebo group and 14, 20, 18, 23, and 15 events in the 10-, 50-, 200-, 500-, and 1,000-mg groups, respectively.

There was one metastatic ovarian cancer in the placebo group, two basal cell carcinomas in a single patient at the 10-mg dose, one laryngeal cancer and one breast cancer in the 50-mg group, one B-cell lymphoma in the 200-mg group, and one adenocarcinoma and two basal cell carcinomas in the 500-mg group. No malignancies were seen in the highest dose group.

Administration of ocrelizumab was tied to a slight decrease in immunoglobulin M levels, but this did not appear to have any clinical significance, since there were no infections associated with this decrease, he said.

Dr. Genovese disclosed financial ties to trial funder Genentech Inc. as well as Biogen Idec Inc., and Hoffmann-LaRoche Ltd.

BOSTON — A single course of the humanized anti-CD20 antibody ocrelizumab was safe and effective for rheumatoid arthritis in a phase I/II trial, Dr. Mark Genovese reported at the annual meeting of the American College of Rheumatology.

Ocrelizumab is similar to the chimeric anti-CD20 antibody rituximab in its ability to deplete B cells, but this second-generation antibody differs in its Fc region by two amino acid sequences, resulting in slightly increased antibody-dependent cytotoxicity and slightly decreased complement-dependent toxicity, Dr. Genovese said.

The trial included 237 rheumatoid arthritis (RA) patients who had an inadequate response to methotrexate and received a single course of ocrelizumab in doses of 10 mg, 50 mg, 200 mg, 500 mg, or 1000 mg or placebo, given by intravenous infusion on days 1 and 15. There was no treatment with corticosteroids before the infusions, and patients remained on a stable 10- to 25-mg/week dose of methotrexate through 72 weeks.

Clinical assessments were done every 4 weeks until week 24, at which time efficacy was evaluated, and every 12 weeks thereafter.

Most patients were women in their 50s, all were rheumatoid factor positive, and their mean disease duration exceeded 10 years. At baseline, patients had moderate to severe RA and had failed on average at least two disease modifying drugs. Slightly fewer than half had tried and failed with a tumor necrosis factor blocker, said Dr. Genovese, a rheumatologist at Stanford (Calif.) University.

Rapid depletion of B cells was seen in patients in all active treatment groups after the infusions, followed by a gradual dose-dependent repletion. Higher doses demonstrated the greatest efficacy at week 24, with ACR50 responses seen among 25%, 20%, and 28% of patients in the 200-, 500-, and 1,000-mg groups. Remission was achieved by 10%, 3%, and 8% of patients in these groups, respectively. Among placebo patients, ACR50 responses and remission were achieved by 7% and 2%, respectively.

The higher doses also showed greater reductions in C-reactive protein and low immunogenicity, he said.

The most frequent adverse events were infusion related, including headaches, nausea, chills, pyrexia, and dizziness. These events were similar across the active treatment groups and occurred more frequently than in the placebo group.

Rates of serious adverse events were similar across all groups, with 15 events being seen in the placebo group and 14, 20, 18, 23, and 15 events in the 10-, 50-, 200-, 500-, and 1,000-mg groups, respectively.

There was one metastatic ovarian cancer in the placebo group, two basal cell carcinomas in a single patient at the 10-mg dose, one laryngeal cancer and one breast cancer in the 50-mg group, one B-cell lymphoma in the 200-mg group, and one adenocarcinoma and two basal cell carcinomas in the 500-mg group. No malignancies were seen in the highest dose group.

Administration of ocrelizumab was tied to a slight decrease in immunoglobulin M levels, but this did not appear to have any clinical significance, since there were no infections associated with this decrease, he said.

Dr. Genovese disclosed financial ties to trial funder Genentech Inc. as well as Biogen Idec Inc., and Hoffmann-LaRoche Ltd.

Diacerein is safe and effective for reducing osteoarthritis-associated pain, and its effects persisted for at least 3 months after treatment was stopped in a randomized, double-blind, placebo-controlled, multi-center study.

The anthraquinone derivative is approved for use in several European countries but not in the United States.

An intent-to-treat analysis was carried out on 165 patients randomized to receive 50-mg diacerein capsules (82 patients) or placebo twice daily for 3 months. Most patients had bilateral knee OA, and most were taking nonsteroidal anti-inflammatory drugs. The majority were female and the mean duration of OA was 6.5 years (Arthritis Rheum. 2007;56:4055-64).

The two primary end points were the percentage change in baseline pain as recorded on a 100-mm visual analog scale (VAS) in section A of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and change in score on the total WOMAC from baseline to the fifth month.

“Diacerein showed statistically significant superiority over placebo (P less than .0001) for the primary efficacy criterion,” wrote Dr. Karel Pavelka, of Charles University, Prague, and his associates. Changes in pain on a 100-mm normalized scale were “already significantly different in favor of diacerein at month 2” and the level of pain “decreased further in the diacerein group by the end of treatment (month 3) (P = .0006) and persisted at this level not only at months 4 and 5 … but also at month 6.”

The absolute change in pain at month 3 for the treatment group was 21.6 mm, versus 9.4 mm in the placebo group. At month 5, the treatment group change persisted, at 23.3 mm, versus 9.5 mm in the placebo group.

The other primary end point—change on the total WOMAC—“was also significantly different (P less than .0001) compared with placebo at month 5,” wrote the investigators. The total WOMAC score at baseline was 1,251 and 1,183 in the diacerein and placebo groups, respectively. The diacerein group's score dropped to 834 at month 3 versus 982 in the placebo group, and diacerein patients had a total score of 733 at month 6 versus 1,011 for placebo patients (P = .0045 at month 3 and P less than .0001 at month 6).

A former consultant for Negma, a French company that marketed the drug, Dr. Roy Altman said in an interview that the drug was put before the Food and Drug Administration several times in the last decade. But the “shifting sands” of the agency's clinical trial data requirements prevented the drug from ever gaining approval. (A representative from the FDA's Center for Drug Evaluation and Research would not comment on drugs that had not been approved.)

The Osteoarthritis Research Society International's new therapeutic guidelines are likely to give “approval for diacerein for OA, but not a high recommendation,” according to Dr. Altman, a visiting professor in the division of rheumatology of the University of California, Los Angeles.

The study was supported by a joint grant from TRB Chemedica International SA and Glynn Brothers Chemicals AG, two Switzerland-based companies.

Unpublished international guidelines likely will approve the use of diacerein for OA pain. DR. ALTMAN

Diacerein is safe and effective for reducing osteoarthritis-associated pain, and its effects persisted for at least 3 months after treatment was stopped in a randomized, double-blind, placebo-controlled, multi-center study.

The anthraquinone derivative is approved for use in several European countries but not in the United States.

An intent-to-treat analysis was carried out on 165 patients randomized to receive 50-mg diacerein capsules (82 patients) or placebo twice daily for 3 months. Most patients had bilateral knee OA, and most were taking nonsteroidal anti-inflammatory drugs. The majority were female and the mean duration of OA was 6.5 years (Arthritis Rheum. 2007;56:4055-64).

The two primary end points were the percentage change in baseline pain as recorded on a 100-mm visual analog scale (VAS) in section A of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and change in score on the total WOMAC from baseline to the fifth month.

“Diacerein showed statistically significant superiority over placebo (P less than .0001) for the primary efficacy criterion,” wrote Dr. Karel Pavelka, of Charles University, Prague, and his associates. Changes in pain on a 100-mm normalized scale were “already significantly different in favor of diacerein at month 2” and the level of pain “decreased further in the diacerein group by the end of treatment (month 3) (P = .0006) and persisted at this level not only at months 4 and 5 … but also at month 6.”

The absolute change in pain at month 3 for the treatment group was 21.6 mm, versus 9.4 mm in the placebo group. At month 5, the treatment group change persisted, at 23.3 mm, versus 9.5 mm in the placebo group.

The other primary end point—change on the total WOMAC—“was also significantly different (P less than .0001) compared with placebo at month 5,” wrote the investigators. The total WOMAC score at baseline was 1,251 and 1,183 in the diacerein and placebo groups, respectively. The diacerein group's score dropped to 834 at month 3 versus 982 in the placebo group, and diacerein patients had a total score of 733 at month 6 versus 1,011 for placebo patients (P = .0045 at month 3 and P less than .0001 at month 6).

A former consultant for Negma, a French company that marketed the drug, Dr. Roy Altman said in an interview that the drug was put before the Food and Drug Administration several times in the last decade. But the “shifting sands” of the agency's clinical trial data requirements prevented the drug from ever gaining approval. (A representative from the FDA's Center for Drug Evaluation and Research would not comment on drugs that had not been approved.)

The Osteoarthritis Research Society International's new therapeutic guidelines are likely to give “approval for diacerein for OA, but not a high recommendation,” according to Dr. Altman, a visiting professor in the division of rheumatology of the University of California, Los Angeles.

The study was supported by a joint grant from TRB Chemedica International SA and Glynn Brothers Chemicals AG, two Switzerland-based companies.

Unpublished international guidelines likely will approve the use of diacerein for OA pain. DR. ALTMAN

Diacerein is safe and effective for reducing osteoarthritis-associated pain, and its effects persisted for at least 3 months after treatment was stopped in a randomized, double-blind, placebo-controlled, multi-center study.

The anthraquinone derivative is approved for use in several European countries but not in the United States.

An intent-to-treat analysis was carried out on 165 patients randomized to receive 50-mg diacerein capsules (82 patients) or placebo twice daily for 3 months. Most patients had bilateral knee OA, and most were taking nonsteroidal anti-inflammatory drugs. The majority were female and the mean duration of OA was 6.5 years (Arthritis Rheum. 2007;56:4055-64).

The two primary end points were the percentage change in baseline pain as recorded on a 100-mm visual analog scale (VAS) in section A of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and change in score on the total WOMAC from baseline to the fifth month.

“Diacerein showed statistically significant superiority over placebo (P less than .0001) for the primary efficacy criterion,” wrote Dr. Karel Pavelka, of Charles University, Prague, and his associates. Changes in pain on a 100-mm normalized scale were “already significantly different in favor of diacerein at month 2” and the level of pain “decreased further in the diacerein group by the end of treatment (month 3) (P = .0006) and persisted at this level not only at months 4 and 5 … but also at month 6.”

The absolute change in pain at month 3 for the treatment group was 21.6 mm, versus 9.4 mm in the placebo group. At month 5, the treatment group change persisted, at 23.3 mm, versus 9.5 mm in the placebo group.

The other primary end point—change on the total WOMAC—“was also significantly different (P less than .0001) compared with placebo at month 5,” wrote the investigators. The total WOMAC score at baseline was 1,251 and 1,183 in the diacerein and placebo groups, respectively. The diacerein group's score dropped to 834 at month 3 versus 982 in the placebo group, and diacerein patients had a total score of 733 at month 6 versus 1,011 for placebo patients (P = .0045 at month 3 and P less than .0001 at month 6).

A former consultant for Negma, a French company that marketed the drug, Dr. Roy Altman said in an interview that the drug was put before the Food and Drug Administration several times in the last decade. But the “shifting sands” of the agency's clinical trial data requirements prevented the drug from ever gaining approval. (A representative from the FDA's Center for Drug Evaluation and Research would not comment on drugs that had not been approved.)

The Osteoarthritis Research Society International's new therapeutic guidelines are likely to give “approval for diacerein for OA, but not a high recommendation,” according to Dr. Altman, a visiting professor in the division of rheumatology of the University of California, Los Angeles.

The study was supported by a joint grant from TRB Chemedica International SA and Glynn Brothers Chemicals AG, two Switzerland-based companies.

Unpublished international guidelines likely will approve the use of diacerein for OA pain. DR. ALTMAN

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.

BOSTON — Inhibition of two key immunoregulatory cytokines known to be involved in the pathogenesis of psoriasis and other autoimmune diseases led to significant improvements in psoriatic arthritis, judging from data from a new study, Dr. Alice B. Gottlieb reported at the annual meeting of the American College of Rheumatology.

Interleukin (IL)-12 and IL-23 play important roles in coordinating innate and adaptive immune responses, binding via the p40 subunit to the IL-12 receptor β1 on the surface of T cells and natural killer cells. Among the functions of IL-12 in psoriasis are T-cell differentiation and the facilitation of T-cell homing to the skin (Cell Immunol. 2007;247:1-11).

The drug ustekinumab now has also been evaluated in active psoriatic arthritis (PsA) in a multicenter, double-blind study that included 146 patients randomized to receive the active treatment at weeks 0, 1, 2, and 3, followed by placebo at weeks 12 and 16, or placebo at weeks 0, 1, 2, and 3 followed by the active treatment at weeks 12 and 16. They were then followed through week 36.

The primary end point was the percentage of patients achieving a response on the American College of Rheumatology (ACR) 20 scale at week 12. Patients in the active treatment group received four subcutaneous doses of either 63 mg (n = 59) or 90 mg (n = 17) of ustekinumab. This inconsistency in dose resulted from a change in preparation of the drug during the study, said Dr. Gottlieb, of the Tufts-New England Medical Center, Boston.

At baseline, the swollen joint count was 12, and the tender joint count was 22. Approximately 20% of patients were on concurrent methotrexate, and half were on concurrent NSAIDs, but none was taking oral corticosteroids. At week 12, 42% of patients in the ustekinumab group had achieved the primary end point, compared with 14% of patients in the placebo group.

By week 36, patients initially randomized to ustekinumab had not received any active treatment for 32 week—yet three-quarters maintained an ACR 20 response. “You do not see this with any of the anti-[tumor necrosis factor] agents,” Dr. Gottlieb said.

Moreover, patients who initially received placebo but then were crossed over to the active treatment group at week 12 also went on to have rapid and sustained responses, she said.

A higher proportion of patients in the active treatment group also reached ACR 50 and ACR 70 responses. A total of 25% and 11% of patients in the ustekinumab achieved these levels of response, compared with 7% and 0% of those in the placebo group.

The decrease from baseline on the Health Assessment Questionnaire disability index at week 12 was greater in the ustekinumab group (mean change −0.31), compared with the placebo group (−0.04).

A total of 52% of patients receiving the active treatment achieved a PASI 75 result at week 12, as did 6% of those receiving placebo. The 85% of patients with at least 3% body surface area psoriasis involvement who received ustekinumab had a greater decrease in the Dermatology Life Quality Index (mean change −8.6), compared with those who received placebo (−0.8). All of these differences were statistically significant.

There were no serious adverse events through week 12 in the active treatment group, whereas in the placebo group there was one report of myocardial infarction, one of gastric ulcer hemorrhage, and one of chest pain. There were no problems with abnormal laboratory values through week 12, nor were there any cases of tuberculosis or serious opportunistic infections, she said.

Dr. Gottlieb disclosed that she has received research grants and consulting fees from Centocor Research and Development Inc., which funded the trial and makes ustekinumab.