Rheumatoid Arthritis

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

CHICAGO — A host of promising new therapies for rheumatoid arthritis are in development, including the human monoclonal antibody belimumab, Mark C. Genovese, M.D., reported at a symposium sponsored by the American College of Rheumatology.

Belimumab inhibits the activity of B-lymphocyte stimulator (BLyS), a protein that is elevated in the blood and joint fluid of people who have rheumatoid arthritis (RA).

BLyS is believed to contribute to the production of autoantibodies, especially rheumatoid factor, which appears to correlate with disease severity.

An interim analysis of a phase II trial of belimumab (LymphoStat-B) showed a clinical effect at various doses in 283 patients with active moderate to severe RA, said Dr. Genovese, an investigator for Human Genome Sciences, which sponsored the study.

Belimumab also produced statistically significant reductions in all active treatment groups of circulating B cells (CD 20+ and other subsets) and rheumatoid factor, compared with placebo.

“It's an encouraging therapy,” Dr. Genovese told this newspaper. “But that enthusiasm has to be tempered by the fact we have to see more studies.”

Patients were allowed concurrent standard-of-care therapy, including at least one TNF-α inhibitor and up to 10 mg/day of prednisone.

About 73% of patients were receiving background methotrexate. More than one-third of patients (38%) had been failed by at least one TNF-α inhibitor.

Patients were randomized to receive placebo or belimumab in doses of 1 mg/kg, 4 mg/kg, or 10 mg/kg, given intravenously for 24 weeks.

All patients were dosed on days 0, 14, and 28, then every 28 days for the remainder of the 24 weeks.

The study's primary efficacy end point was the achievement of an American College of Rheumatology (ACR) 20 response at 24 weeks.

Among those in the 1-mg/kg group, 36% achieved an ACR 20 response, as did 17% in the placebo group. This between-group difference was statistically significant.

Trends toward a drug benefit were seen in the 4-mg/kg group (28% ACR 20) and in the 10-mg/kg group (29% ACR 20).

Adverse events were similar across treatment groups, and clinically significant infusion reactions were rare, according to a statement by Human Genome Sciences.

Another promising therapy, rituximab, is a monoclonal antibody that targets CD20 on B cells, said Dr. Genovese, chief of clinical services in the division of immunology and rheumatology at Stanford University, Palo Alto, Calif.

A preliminary analysis of phase III data from the Randomized Evaluation of Long-term Efficacy of Rituximab in RA (REFLEX) trial showed that a greater proportion of rituximab-treated patients achieved an ACR 20 at week 24 than those taking placebo, said Dr. Genovese, also a consultant for Genentech Inc., which sponsored the study.

The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with one or more anti-TNF therapies.

The data did not show anything unexpected regarding safety or efficacy, said Stanley B. Cohen, M.D., the principal investigator for the Radiant Research site of the trial.

The findings so far support the hypothesis that “we have a potential therapy that we can use in patients with disease that is refractory to our most potent therapies to date, which are TNF inhibitors,” Dr. Cohen said in an interview.

Detailed results from REFLEX are expected to be presented at the annual congress of the European League Against Rheumatism in June.

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

KEVIN FOLEY, RESEARCH/ANGIE RIES, DESIGN

Skin reactions to tumor necrosis factor-α-blocking drugs for rheumatoid arthritis might be more common and more varied than previous studies have indicated, results of a new prospective study show.

The study authors, led by Marcel Flendrie, M.D., of Radboud University Nijmegen (the Netherlands) Medical Centre, said theirs is the first large prospective study of dermatologic conditions in rheumatoid arthritis (RA) patients taking TNF-α-blocking medications.

Overall, 25% of the 289 patients taking the biologics had a dermatologic event, compared with 13% of the same number of control patients.

The odds ratio for a patient taking the biologics to require a dermatologic referral was 2.26 (Arthritis Res. Ther. 2005;7:R666-76). The study was published online at BioMed Central's Web site on April 4 (www.arthritis-research.com/content/7/3/r666

There seemed to be no characteristic at baseline that predicted which patients might be susceptible to a dermatologic event, the authors said.

In the trial, 289 consecutive patients with RA who were started on TNF-α-blocking therapy—infliximab, etanercept, adalimumab, or the experimental agent lenercept—were compared with 289 patients from a cohort of 500 who have been followed at the medical center since 1985 but who had never taken a TNF-α-blocking agent.

Any patient who visited a dermatologist during the follow-up period was identified, and any new manifestation or exacerbation of a skin disease or any drug-related eruptions were recorded. The researchers also recorded diagnoses, topical and systemic therapeutic actions, outcome of the event, and any information on rechallenge.

Median follow-up time was 2.3 years. Among the patients taking anti-TNF therapy, 70 (24%) had received more than one agent, 8 (3%) had a history of taking more than two.

Overall, 167 patients were given infliximab, 108 received adalimumab, 78 received etanercept, and 31 were treated with lenercept. In total, there were 128 dermatologic events in the TNF group; 56 events occurred with adalimumab, 49 with infliximab, 16 with etanercept, and 13 with lenercept.

Skin infections accounted for the largest proportion of these therapy-related events, with 33 fungal, bacterial, and viral infections recorded. TNF-α-blocking therapies are known to increase susceptibility to infections, and the study findings suggest that the immunosuppressive agents might also make patients more vulnerable to skin infections, said the authors.

Eczema was diagnosed 20 times in 19 patients, and 3 patients stopped therapy as a result. One patient was hospitalized. The others were treated with topical corticosteroids.

There were frequent cases of drug-related eruptions in the first 5 months, in particular, said the authors.

Most common was a combination of exanthema, urticarial eruptions, lichenoid skin lesions, and purpura. Of 15 patients diagnosed with an eruption, 7 stopped therapy, and 8 continued. One patient was hospitalized.

In smaller numbers, patients also experienced ulcers, benign and malignant skin tumors, vasculitis, actinic keratosis, edema, chronic venous insufficiency/varices, xerosis cutis, and stasis dermatitis.

The occurrence of psoriasiform eruptions in three patients was “particularly interesting,” given that etanercept is approved for psoriasis, and infliximab may soon get that approval, the researchers said.

The time between the start of therapy and onset of skin conditions varied, but some events looked more likely to be drug related, including the eruptions, cutaneous vasculitis, a case of systemic lupus erythematosus, dermatomyositis, and a lymphomatoid papulosis-like eruption, the authors continued.

Overall, 19 of the 72 patients who experienced skin problems stopped taking the TNF-α-blocking therapy.

Skin reactions to tumor necrosis factor-α-blocking drugs for rheumatoid arthritis might be more common and more varied than previous studies have indicated, results of a new prospective study show.

The study authors, led by Marcel Flendrie, M.D., of Radboud University Nijmegen (the Netherlands) Medical Centre, said theirs is the first large prospective study of dermatologic conditions in rheumatoid arthritis (RA) patients taking TNF-α-blocking medications.

Overall, 25% of the 289 patients taking the biologics had a dermatologic event, compared with 13% of the same number of control patients.

The odds ratio for a patient taking the biologics to require a dermatologic referral was 2.26 (Arthritis Res. Ther. 2005;7:R666-76). The study was published online at BioMed Central's Web site on April 4 (www.arthritis-research.com/content/7/3/r666

There seemed to be no characteristic at baseline that predicted which patients might be susceptible to a dermatologic event, the authors said.

In the trial, 289 consecutive patients with RA who were started on TNF-α-blocking therapy—infliximab, etanercept, adalimumab, or the experimental agent lenercept—were compared with 289 patients from a cohort of 500 who have been followed at the medical center since 1985 but who had never taken a TNF-α-blocking agent.

Any patient who visited a dermatologist during the follow-up period was identified, and any new manifestation or exacerbation of a skin disease or any drug-related eruptions were recorded. The researchers also recorded diagnoses, topical and systemic therapeutic actions, outcome of the event, and any information on rechallenge.

Median follow-up time was 2.3 years. Among the patients taking anti-TNF therapy, 70 (24%) had received more than one agent, 8 (3%) had a history of taking more than two.

Overall, 167 patients were given infliximab, 108 received adalimumab, 78 received etanercept, and 31 were treated with lenercept. In total, there were 128 dermatologic events in the TNF group; 56 events occurred with adalimumab, 49 with infliximab, 16 with etanercept, and 13 with lenercept.

Skin infections accounted for the largest proportion of these therapy-related events, with 33 fungal, bacterial, and viral infections recorded. TNF-α-blocking therapies are known to increase susceptibility to infections, and the study findings suggest that the immunosuppressive agents might also make patients more vulnerable to skin infections, said the authors.

Eczema was diagnosed 20 times in 19 patients, and 3 patients stopped therapy as a result. One patient was hospitalized. The others were treated with topical corticosteroids.

There were frequent cases of drug-related eruptions in the first 5 months, in particular, said the authors.

Most common was a combination of exanthema, urticarial eruptions, lichenoid skin lesions, and purpura. Of 15 patients diagnosed with an eruption, 7 stopped therapy, and 8 continued. One patient was hospitalized.

In smaller numbers, patients also experienced ulcers, benign and malignant skin tumors, vasculitis, actinic keratosis, edema, chronic venous insufficiency/varices, xerosis cutis, and stasis dermatitis.

The occurrence of psoriasiform eruptions in three patients was “particularly interesting,” given that etanercept is approved for psoriasis, and infliximab may soon get that approval, the researchers said.

The time between the start of therapy and onset of skin conditions varied, but some events looked more likely to be drug related, including the eruptions, cutaneous vasculitis, a case of systemic lupus erythematosus, dermatomyositis, and a lymphomatoid papulosis-like eruption, the authors continued.

Overall, 19 of the 72 patients who experienced skin problems stopped taking the TNF-α-blocking therapy.

Skin reactions to tumor necrosis factor-α-blocking drugs for rheumatoid arthritis might be more common and more varied than previous studies have indicated, results of a new prospective study show.

The study authors, led by Marcel Flendrie, M.D., of Radboud University Nijmegen (the Netherlands) Medical Centre, said theirs is the first large prospective study of dermatologic conditions in rheumatoid arthritis (RA) patients taking TNF-α-blocking medications.

Overall, 25% of the 289 patients taking the biologics had a dermatologic event, compared with 13% of the same number of control patients.

The odds ratio for a patient taking the biologics to require a dermatologic referral was 2.26 (Arthritis Res. Ther. 2005;7:R666-76). The study was published online at BioMed Central's Web site on April 4 (www.arthritis-research.com/content/7/3/r666

There seemed to be no characteristic at baseline that predicted which patients might be susceptible to a dermatologic event, the authors said.

In the trial, 289 consecutive patients with RA who were started on TNF-α-blocking therapy—infliximab, etanercept, adalimumab, or the experimental agent lenercept—were compared with 289 patients from a cohort of 500 who have been followed at the medical center since 1985 but who had never taken a TNF-α-blocking agent.

Any patient who visited a dermatologist during the follow-up period was identified, and any new manifestation or exacerbation of a skin disease or any drug-related eruptions were recorded. The researchers also recorded diagnoses, topical and systemic therapeutic actions, outcome of the event, and any information on rechallenge.

Median follow-up time was 2.3 years. Among the patients taking anti-TNF therapy, 70 (24%) had received more than one agent, 8 (3%) had a history of taking more than two.

Overall, 167 patients were given infliximab, 108 received adalimumab, 78 received etanercept, and 31 were treated with lenercept. In total, there were 128 dermatologic events in the TNF group; 56 events occurred with adalimumab, 49 with infliximab, 16 with etanercept, and 13 with lenercept.

Skin infections accounted for the largest proportion of these therapy-related events, with 33 fungal, bacterial, and viral infections recorded. TNF-α-blocking therapies are known to increase susceptibility to infections, and the study findings suggest that the immunosuppressive agents might also make patients more vulnerable to skin infections, said the authors.

Eczema was diagnosed 20 times in 19 patients, and 3 patients stopped therapy as a result. One patient was hospitalized. The others were treated with topical corticosteroids.

There were frequent cases of drug-related eruptions in the first 5 months, in particular, said the authors.

Most common was a combination of exanthema, urticarial eruptions, lichenoid skin lesions, and purpura. Of 15 patients diagnosed with an eruption, 7 stopped therapy, and 8 continued. One patient was hospitalized.

In smaller numbers, patients also experienced ulcers, benign and malignant skin tumors, vasculitis, actinic keratosis, edema, chronic venous insufficiency/varices, xerosis cutis, and stasis dermatitis.

The occurrence of psoriasiform eruptions in three patients was “particularly interesting,” given that etanercept is approved for psoriasis, and infliximab may soon get that approval, the researchers said.

The time between the start of therapy and onset of skin conditions varied, but some events looked more likely to be drug related, including the eruptions, cutaneous vasculitis, a case of systemic lupus erythematosus, dermatomyositis, and a lymphomatoid papulosis-like eruption, the authors continued.

Overall, 19 of the 72 patients who experienced skin problems stopped taking the TNF-α-blocking therapy.

Microfracture significantly improved knee function in patients with isolated full-thickness cartilage defects of the femur, Kai Mithoefer, M.D., reported at the annual meeting of the American Academy of Orthopaedic Surgeons.

His prospective evaluation of the common technique, which involves clearing out defective cartilage and creating a series of holes in the subchondral bone to stimulate growth of fibrocartilaginous repair tissue, showed that best results were obtained in patients who had good repair tissue fill (as opposed to moderate or poor fill), low body mass index (BMI), and symptom duration less than 12 months.

In the study, 48 patients were evaluated, with a minimum 2-year follow-up, using a combination of validated outcomes scores—including the SF-36 and Activities of Daily Living scores—cartilage-sensitive MRI, and a subjective rating. Most patients were male; they averaged 21 years of age.

Patients with good fill grade “had significantly more improvement in all the scores than patients with moderate fill grade,” reported Dr. Mithoefer, of Massachusetts General Hospital, Cambridge. Lower BMI was associated with better functional outcomes. Poor fill grade was associated with limited improvement and decreasing functional scores after 24 months. Patients with poor fill grade also had higher BMI and a longer duration of symptoms, he reported.

In another study of osteoarticular transplantation surgery for large full-thickness cartilage defects of the knee, investigators found that 80% of 58 patients who underwent the procedure demonstrated significant improvement at an average of 36 months, reported Albert W. Pearsall IV, M.D., of the University of South Alabama Knollwood Park Hospital in Mobile.

Microfracture significantly improved knee function in patients with isolated full-thickness cartilage defects of the femur, Kai Mithoefer, M.D., reported at the annual meeting of the American Academy of Orthopaedic Surgeons.

His prospective evaluation of the common technique, which involves clearing out defective cartilage and creating a series of holes in the subchondral bone to stimulate growth of fibrocartilaginous repair tissue, showed that best results were obtained in patients who had good repair tissue fill (as opposed to moderate or poor fill), low body mass index (BMI), and symptom duration less than 12 months.

In the study, 48 patients were evaluated, with a minimum 2-year follow-up, using a combination of validated outcomes scores—including the SF-36 and Activities of Daily Living scores—cartilage-sensitive MRI, and a subjective rating. Most patients were male; they averaged 21 years of age.

Patients with good fill grade “had significantly more improvement in all the scores than patients with moderate fill grade,” reported Dr. Mithoefer, of Massachusetts General Hospital, Cambridge. Lower BMI was associated with better functional outcomes. Poor fill grade was associated with limited improvement and decreasing functional scores after 24 months. Patients with poor fill grade also had higher BMI and a longer duration of symptoms, he reported.

In another study of osteoarticular transplantation surgery for large full-thickness cartilage defects of the knee, investigators found that 80% of 58 patients who underwent the procedure demonstrated significant improvement at an average of 36 months, reported Albert W. Pearsall IV, M.D., of the University of South Alabama Knollwood Park Hospital in Mobile.

Microfracture significantly improved knee function in patients with isolated full-thickness cartilage defects of the femur, Kai Mithoefer, M.D., reported at the annual meeting of the American Academy of Orthopaedic Surgeons.

His prospective evaluation of the common technique, which involves clearing out defective cartilage and creating a series of holes in the subchondral bone to stimulate growth of fibrocartilaginous repair tissue, showed that best results were obtained in patients who had good repair tissue fill (as opposed to moderate or poor fill), low body mass index (BMI), and symptom duration less than 12 months.

In the study, 48 patients were evaluated, with a minimum 2-year follow-up, using a combination of validated outcomes scores—including the SF-36 and Activities of Daily Living scores—cartilage-sensitive MRI, and a subjective rating. Most patients were male; they averaged 21 years of age.

Patients with good fill grade “had significantly more improvement in all the scores than patients with moderate fill grade,” reported Dr. Mithoefer, of Massachusetts General Hospital, Cambridge. Lower BMI was associated with better functional outcomes. Poor fill grade was associated with limited improvement and decreasing functional scores after 24 months. Patients with poor fill grade also had higher BMI and a longer duration of symptoms, he reported.

In another study of osteoarticular transplantation surgery for large full-thickness cartilage defects of the knee, investigators found that 80% of 58 patients who underwent the procedure demonstrated significant improvement at an average of 36 months, reported Albert W. Pearsall IV, M.D., of the University of South Alabama Knollwood Park Hospital in Mobile.

Physicians who urged conservative treatment for neck pain—including a waiting period for imaging studies—were peppered with questions at the annual meeting of the American Academy of Orthopaedic Surgeons about how to determine whether and when neck pain stems from the disk.

“Unfortunately, we have no clear guidelines on how to determine whether neck pain is coming from the disk,” said Raj Rao, M.D. “If it's worse with extension, I'm more inclined to believe that this may be [disk-related] pain. But number one is just my instinctive feel.”

Dr. Rao, director of spine surgery at the Medical College of Wisconsin, Milwaukee, and Jeffrey C. Wang, M.D., had both emphasized during a session on the cervical spine that neck pain—which 50%-70% of people experience at some point—most often resolves with conservative measures.

“If there are no urgent findings, no history of trauma, no suspicion of neoplasm or infection, and [the patient doesn't] have a worsening neurologic deficit, there is an appropriate period of time you can wait before obtaining any imaging studies whatsoever,” said Dr. Wang, chief of the spine service at the UCLA School of Medicine.

He recommended waiting at least 4 weeks before performing plain radiography of the cervical spine and evaluating radiographs as thoroughly as possible before considering MRI.

“The newer thinking is that [in addition to many other factors] we want to look at the amount of space available for the spinal cord and the neurologic elements,” Dr. Wang said. “And remember, the oblique views are important.”

Despite recent concerns about nonsteroidal anti-inflammatory drugs, the drugs are still a first line of treatment for patients with neck pain, Dr. Wang said. Corticosteroids “do not have a role in neck pain alone without any neurologic symptoms,” and narcotics and muscle relaxants are appropriate only for short-term use, he said.

“Physical therapy,” he emphasized, “is very, very valuable. We can now send patients in the acute phase—there are many more modalities to control pain.”

Dr. Wang and Dr. Rao responded to physicians who said they were frustrated with patients involved in legal actions who seek their opinion on whether motor vehicle accidents caused their neck pain—and specifically whether the accidents caused disk herniations.

The two physicians urged their colleagues to be cautious. “My party-line answer is that I can't make a determination of whether [their neck pain] is caused by the accident. … And I rarely see patients with an acute herniated disk from a car accident,” Dr. Wang said.

“We have to remember we're dealing with pain. There are so many inputs,” Dr. Rao said. “It's very difficult to quantify how much of the pain is coming from the patient's neck, the patient's disk, and elsewhere.”

Studies show that one-third of patients who suffer whiplash in motor vehicle accidents will have symptoms for 1 year, and 25% will have symptoms for up to 2 years, Dr. Wang said.

The physicians also responded cautiously to a question from the session moderator Jeffrey S. Fischgrund, M.D., about the role of diskograms. “I'm sure that within 2 years, cervical disk replacements will become available, and there's no question that people will be looking at this as a treatment for neck pain. And I'm sure we'll see a lot more diskograms. … Will this be an option for people with neck pain?” said Dr. Fischgrund, who practices in Southfield, Mich.

Some physicians at UCLA order diskograms of the cervical spine, but “I tend not to get diskograms,” Dr. Wang said. “I'm not quite sure what to make of them.”

MRI (left) helps identify severe narrowing of the spinal cord. An x-ray shows degenerative changes. PHOTOS COURTESY DR. JEFFREY C. WANG

Physicians who urged conservative treatment for neck pain—including a waiting period for imaging studies—were peppered with questions at the annual meeting of the American Academy of Orthopaedic Surgeons about how to determine whether and when neck pain stems from the disk.

“Unfortunately, we have no clear guidelines on how to determine whether neck pain is coming from the disk,” said Raj Rao, M.D. “If it's worse with extension, I'm more inclined to believe that this may be [disk-related] pain. But number one is just my instinctive feel.”

Dr. Rao, director of spine surgery at the Medical College of Wisconsin, Milwaukee, and Jeffrey C. Wang, M.D., had both emphasized during a session on the cervical spine that neck pain—which 50%-70% of people experience at some point—most often resolves with conservative measures.

“If there are no urgent findings, no history of trauma, no suspicion of neoplasm or infection, and [the patient doesn't] have a worsening neurologic deficit, there is an appropriate period of time you can wait before obtaining any imaging studies whatsoever,” said Dr. Wang, chief of the spine service at the UCLA School of Medicine.

He recommended waiting at least 4 weeks before performing plain radiography of the cervical spine and evaluating radiographs as thoroughly as possible before considering MRI.

“The newer thinking is that [in addition to many other factors] we want to look at the amount of space available for the spinal cord and the neurologic elements,” Dr. Wang said. “And remember, the oblique views are important.”

Despite recent concerns about nonsteroidal anti-inflammatory drugs, the drugs are still a first line of treatment for patients with neck pain, Dr. Wang said. Corticosteroids “do not have a role in neck pain alone without any neurologic symptoms,” and narcotics and muscle relaxants are appropriate only for short-term use, he said.

“Physical therapy,” he emphasized, “is very, very valuable. We can now send patients in the acute phase—there are many more modalities to control pain.”

Dr. Wang and Dr. Rao responded to physicians who said they were frustrated with patients involved in legal actions who seek their opinion on whether motor vehicle accidents caused their neck pain—and specifically whether the accidents caused disk herniations.

The two physicians urged their colleagues to be cautious. “My party-line answer is that I can't make a determination of whether [their neck pain] is caused by the accident. … And I rarely see patients with an acute herniated disk from a car accident,” Dr. Wang said.

“We have to remember we're dealing with pain. There are so many inputs,” Dr. Rao said. “It's very difficult to quantify how much of the pain is coming from the patient's neck, the patient's disk, and elsewhere.”

Studies show that one-third of patients who suffer whiplash in motor vehicle accidents will have symptoms for 1 year, and 25% will have symptoms for up to 2 years, Dr. Wang said.

The physicians also responded cautiously to a question from the session moderator Jeffrey S. Fischgrund, M.D., about the role of diskograms. “I'm sure that within 2 years, cervical disk replacements will become available, and there's no question that people will be looking at this as a treatment for neck pain. And I'm sure we'll see a lot more diskograms. … Will this be an option for people with neck pain?” said Dr. Fischgrund, who practices in Southfield, Mich.

Some physicians at UCLA order diskograms of the cervical spine, but “I tend not to get diskograms,” Dr. Wang said. “I'm not quite sure what to make of them.”

MRI (left) helps identify severe narrowing of the spinal cord. An x-ray shows degenerative changes. PHOTOS COURTESY DR. JEFFREY C. WANG

Physicians who urged conservative treatment for neck pain—including a waiting period for imaging studies—were peppered with questions at the annual meeting of the American Academy of Orthopaedic Surgeons about how to determine whether and when neck pain stems from the disk.

“Unfortunately, we have no clear guidelines on how to determine whether neck pain is coming from the disk,” said Raj Rao, M.D. “If it's worse with extension, I'm more inclined to believe that this may be [disk-related] pain. But number one is just my instinctive feel.”

Dr. Rao, director of spine surgery at the Medical College of Wisconsin, Milwaukee, and Jeffrey C. Wang, M.D., had both emphasized during a session on the cervical spine that neck pain—which 50%-70% of people experience at some point—most often resolves with conservative measures.

“If there are no urgent findings, no history of trauma, no suspicion of neoplasm or infection, and [the patient doesn't] have a worsening neurologic deficit, there is an appropriate period of time you can wait before obtaining any imaging studies whatsoever,” said Dr. Wang, chief of the spine service at the UCLA School of Medicine.

He recommended waiting at least 4 weeks before performing plain radiography of the cervical spine and evaluating radiographs as thoroughly as possible before considering MRI.

“The newer thinking is that [in addition to many other factors] we want to look at the amount of space available for the spinal cord and the neurologic elements,” Dr. Wang said. “And remember, the oblique views are important.”

Despite recent concerns about nonsteroidal anti-inflammatory drugs, the drugs are still a first line of treatment for patients with neck pain, Dr. Wang said. Corticosteroids “do not have a role in neck pain alone without any neurologic symptoms,” and narcotics and muscle relaxants are appropriate only for short-term use, he said.

“Physical therapy,” he emphasized, “is very, very valuable. We can now send patients in the acute phase—there are many more modalities to control pain.”

Dr. Wang and Dr. Rao responded to physicians who said they were frustrated with patients involved in legal actions who seek their opinion on whether motor vehicle accidents caused their neck pain—and specifically whether the accidents caused disk herniations.

The two physicians urged their colleagues to be cautious. “My party-line answer is that I can't make a determination of whether [their neck pain] is caused by the accident. … And I rarely see patients with an acute herniated disk from a car accident,” Dr. Wang said.

“We have to remember we're dealing with pain. There are so many inputs,” Dr. Rao said. “It's very difficult to quantify how much of the pain is coming from the patient's neck, the patient's disk, and elsewhere.”

Studies show that one-third of patients who suffer whiplash in motor vehicle accidents will have symptoms for 1 year, and 25% will have symptoms for up to 2 years, Dr. Wang said.

The physicians also responded cautiously to a question from the session moderator Jeffrey S. Fischgrund, M.D., about the role of diskograms. “I'm sure that within 2 years, cervical disk replacements will become available, and there's no question that people will be looking at this as a treatment for neck pain. And I'm sure we'll see a lot more diskograms. … Will this be an option for people with neck pain?” said Dr. Fischgrund, who practices in Southfield, Mich.

Some physicians at UCLA order diskograms of the cervical spine, but “I tend not to get diskograms,” Dr. Wang said. “I'm not quite sure what to make of them.”

MRI (left) helps identify severe narrowing of the spinal cord. An x-ray shows degenerative changes. PHOTOS COURTESY DR. JEFFREY C. WANG

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

CHICAGO — The withdrawal of rofecoxib and valdecoxib from the market may give an even greater number of arthritis patients the impetus to try nonpharmacologic therapies, Sharon L. Kolasinski, M.D., said at a symposium sponsored by the American College of Rheumatology.

Already, roughly half of adults in the United States have tried complementary and alternative medicines (CAM), and patients with rheumatoid arthritis (RA) are among the highest users, said Kolasinski, assistant professor of medicine and chief of clinical services at the University of Pennsylvania School of Medicine, Philadelphia.

This trend isn't all bad as some alternative therapies can help reduce pain and keep the arthritis patient active, she said.

“Nonpharmacologic therapies are an important part of what our patients are actually choosing to use whether we suggest it or not,” said Dr. Kolasinski.

“The evidence suggests that mind-body interventions can be of considerable benefit including coping with chronic pain, and perhaps we should consider them more often.”

There is a substantial body of evidence-based research supporting the use of mind-body interventions such as meditation, cognitive behavioral therapy, and biofeedback. Additionally, tai chi, yoga, and acupuncture may be appropriate adjunctive therapies in some patients.

Dr. Kolasinski said the evidence does not support the use of magnetic bracelets or mattress pads, although copper bracelets are a common sight in many rheumatologists' offices.

An intriguing study of 20 RA patients demonstrated an American College of Rheumatology (ACR) 20 response in half of the patients practicing tai chi, and no similar response in patients enrolled in a stretching and wellness education program for 12 weeks.

Dr. Kolasinski and colleagues at the university found that 8 weekly sessions of yoga significantly improved Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and disability scores in seven women with OA. Stiffness also improved, however, not significantly, she said.

A follow-up gait study to determine if the effects were merely due to increased personal attention, showed that walking speed increased after yoga (Osteoarthritis and Cartilage 2003;11:S44). The results suggest that the regimen may be appropriate for patients with valgus knee deformities, however, it may not be for those with varus deformities, she said.

There are few data on the value of acupuncture in RA, but a definitive study in patients with knee osteoarthritis (OA) concluded that acupuncture is a reasonable adjunctive therapy for pain relief, particularly for patients without other options.

Relative to a sham control group, significant improvements in WOMAC pain and function scores were reported in 570 knee OA patients who previously had been treated with high-dose drug therapy and who had received 23 acupuncture sessions over 26 weeks (Ann. Intern. Med. 2004;141:901-10).

In particular, WOMAC function scores were nearly 3 points better in the true acupuncture group compared with function scores in the sham group.

Differences between the groups were not significant, however, in WOMAC measures of pain or global assessment, according to the investigators who were based at the University of Maryland School of Medicine, Baltimore.

High dropout rates are common in nonpharmacologic therapy trials, suggesting that physicians may want to propose a variety of adjunctive therapies to help keep arthritis patients physically active, she said.

WASHINGTON — Osteocapsular arthroscopy aimed at reshaping the glenoid bone may—with more long-term experience—be proven an effective treatment for patients with glenohumeral osteoarthritis who do not desire total shoulder replacement, Scott Steinmann, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

At this point, it's clear that younger patients with more severe arthritis do not benefit much from debridement, making other alternatives to total shoulder replacement desirable, said Dr. Steinmann of the Mayo Clinic in Rochester, Minn.

There are few reports in the literature and no significant long-term follow-up of patients who have undergone arthroscopic glenoidplasty, a new, relatively aggressive arthroscopic procedure.

However, a 3-year mean follow-up of 14 patients whom Dr. Steinmann and his colleagues treated with the procedure has revealed significant pain relief and high patient satisfaction.

“When we've asked patients how they felt, they [have said] they liked the procedure,” said Dr. Steinmann. “I think they liked a couple small holes and being told they could do whatever they want afterward. They agree the surgery was worthwhile. … But we definitely need to follow them longer.”

Total shoulder replacement remains the standard treatment, but a significant number of replacements show that the glenoid loosens over time.

Some patients—like the ranchers and farmers who Dr. Steinmann treats—are young and active and “could put a prosthesis in jeopardy,” he said. “Some also tell me, 'I don't want any metal or plastic in my body.'”

Arthroscopic options for glenohumeral arthritis range from the simplest option of synovectomy and removal of loose bodies, to the more extensive option of capsular resection and recontouring of the glenoid and humerus.

Dr. Steinmann said he believes the more aggressive approach may prove the most promising for patients with extensive arthritis.

It usually involves synovectomy, osteophyte removal, and capsule release but goes further by involving the conversion of a biconcave glenoid into a single concavity—a change that, theoretically, can restore the position of the humeral head, reducing the posterior subluxation and helping to relax contracted soft tissues.

Restoration of a single concavity may also increase the surface area of the glenohumeral articulation, decreasing joint pressure, he said.

Axillary radiographs taken in his 14 patients show that glenoid depth can be increased by about 3 mm—“a rough measurement, but something to hang our hat on,” he said.

Dr. Steinmann's patients were about 50 years old, on average; 10 of the 14 had previous osteoarthritis. They all had impingement pain at the end of motion, and about half had rest pain, indicating the presence of synovitis. They had no pain with glenohumeral compression or rotation.

The return of function is much less predictable with this procedure than pain relief, Dr. Steinmann said. “Essentially, the range of motion, we're telling patients, will be very similar to what they have,” he said. In a total shoulder replacement, “I usually try to restore much more motion.”

What impact, if any, the surgery may have on a surgeon's ability to perform total shoulder replacement later on is unclear.

“One question is, what happens when you cut out that cartilage and start burring down the glenoid? Does it ruin the chance to do a total shoulder later? We need to follow patients longer.”

WASHINGTON — Osteocapsular arthroscopy aimed at reshaping the glenoid bone may—with more long-term experience—be proven an effective treatment for patients with glenohumeral osteoarthritis who do not desire total shoulder replacement, Scott Steinmann, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

At this point, it's clear that younger patients with more severe arthritis do not benefit much from debridement, making other alternatives to total shoulder replacement desirable, said Dr. Steinmann of the Mayo Clinic in Rochester, Minn.

There are few reports in the literature and no significant long-term follow-up of patients who have undergone arthroscopic glenoidplasty, a new, relatively aggressive arthroscopic procedure.

However, a 3-year mean follow-up of 14 patients whom Dr. Steinmann and his colleagues treated with the procedure has revealed significant pain relief and high patient satisfaction.

“When we've asked patients how they felt, they [have said] they liked the procedure,” said Dr. Steinmann. “I think they liked a couple small holes and being told they could do whatever they want afterward. They agree the surgery was worthwhile. … But we definitely need to follow them longer.”

Total shoulder replacement remains the standard treatment, but a significant number of replacements show that the glenoid loosens over time.

Some patients—like the ranchers and farmers who Dr. Steinmann treats—are young and active and “could put a prosthesis in jeopardy,” he said. “Some also tell me, 'I don't want any metal or plastic in my body.'”

Arthroscopic options for glenohumeral arthritis range from the simplest option of synovectomy and removal of loose bodies, to the more extensive option of capsular resection and recontouring of the glenoid and humerus.

Dr. Steinmann said he believes the more aggressive approach may prove the most promising for patients with extensive arthritis.

It usually involves synovectomy, osteophyte removal, and capsule release but goes further by involving the conversion of a biconcave glenoid into a single concavity—a change that, theoretically, can restore the position of the humeral head, reducing the posterior subluxation and helping to relax contracted soft tissues.

Restoration of a single concavity may also increase the surface area of the glenohumeral articulation, decreasing joint pressure, he said.

Axillary radiographs taken in his 14 patients show that glenoid depth can be increased by about 3 mm—“a rough measurement, but something to hang our hat on,” he said.

Dr. Steinmann's patients were about 50 years old, on average; 10 of the 14 had previous osteoarthritis. They all had impingement pain at the end of motion, and about half had rest pain, indicating the presence of synovitis. They had no pain with glenohumeral compression or rotation.

The return of function is much less predictable with this procedure than pain relief, Dr. Steinmann said. “Essentially, the range of motion, we're telling patients, will be very similar to what they have,” he said. In a total shoulder replacement, “I usually try to restore much more motion.”

What impact, if any, the surgery may have on a surgeon's ability to perform total shoulder replacement later on is unclear.

“One question is, what happens when you cut out that cartilage and start burring down the glenoid? Does it ruin the chance to do a total shoulder later? We need to follow patients longer.”

WASHINGTON — Osteocapsular arthroscopy aimed at reshaping the glenoid bone may—with more long-term experience—be proven an effective treatment for patients with glenohumeral osteoarthritis who do not desire total shoulder replacement, Scott Steinmann, M.D., said at the annual meeting of the American Academy of Orthopaedic Surgeons.

At this point, it's clear that younger patients with more severe arthritis do not benefit much from debridement, making other alternatives to total shoulder replacement desirable, said Dr. Steinmann of the Mayo Clinic in Rochester, Minn.

There are few reports in the literature and no significant long-term follow-up of patients who have undergone arthroscopic glenoidplasty, a new, relatively aggressive arthroscopic procedure.

However, a 3-year mean follow-up of 14 patients whom Dr. Steinmann and his colleagues treated with the procedure has revealed significant pain relief and high patient satisfaction.

“When we've asked patients how they felt, they [have said] they liked the procedure,” said Dr. Steinmann. “I think they liked a couple small holes and being told they could do whatever they want afterward. They agree the surgery was worthwhile. … But we definitely need to follow them longer.”

Total shoulder replacement remains the standard treatment, but a significant number of replacements show that the glenoid loosens over time.

Some patients—like the ranchers and farmers who Dr. Steinmann treats—are young and active and “could put a prosthesis in jeopardy,” he said. “Some also tell me, 'I don't want any metal or plastic in my body.'”

Arthroscopic options for glenohumeral arthritis range from the simplest option of synovectomy and removal of loose bodies, to the more extensive option of capsular resection and recontouring of the glenoid and humerus.

Dr. Steinmann said he believes the more aggressive approach may prove the most promising for patients with extensive arthritis.

It usually involves synovectomy, osteophyte removal, and capsule release but goes further by involving the conversion of a biconcave glenoid into a single concavity—a change that, theoretically, can restore the position of the humeral head, reducing the posterior subluxation and helping to relax contracted soft tissues.

Restoration of a single concavity may also increase the surface area of the glenohumeral articulation, decreasing joint pressure, he said.

Axillary radiographs taken in his 14 patients show that glenoid depth can be increased by about 3 mm—“a rough measurement, but something to hang our hat on,” he said.

Dr. Steinmann's patients were about 50 years old, on average; 10 of the 14 had previous osteoarthritis. They all had impingement pain at the end of motion, and about half had rest pain, indicating the presence of synovitis. They had no pain with glenohumeral compression or rotation.

The return of function is much less predictable with this procedure than pain relief, Dr. Steinmann said. “Essentially, the range of motion, we're telling patients, will be very similar to what they have,” he said. In a total shoulder replacement, “I usually try to restore much more motion.”

What impact, if any, the surgery may have on a surgeon's ability to perform total shoulder replacement later on is unclear.

“One question is, what happens when you cut out that cartilage and start burring down the glenoid? Does it ruin the chance to do a total shoulder later? We need to follow patients longer.”

VANCOUVER, B.C. — Duloxetine is a safe and effective treatment for fibromyalgia symptoms in both depressed and nondepressed women, Lesley Arnold, M.D., reported at the annual meeting of the American Psychosomatic Society.

Duloxetine (Cymbalta) is approved for the treatment of both major depression and diabetic neuropathic pain. The drug's efficacy in treating both pain and depression—which often co-occur in fibromyalgia—is probably due to its dual action as a selective serotonin and norepinephrine reuptake inhibitor, said Dr. Arnold, a psychiatrist who is director of women's health research at the University of Cincinnati.

In one of two 12-week studies funded by Lilly Research Laboratories, a total of 354 adult women who met the American College of Rheumatology's criteria for primary fibromyalgia were randomized to receive 60 mg of duloxetine once a day (118), 60 mg twice daily (116), or placebo (120).

Significant differences in the Brief Pain Inventory (BPI) average 24-hour pain score and the Fibromyalgia Impact Questionnaire (FIQ) were seen within 1 week in both the 60 mg/day and 120 mg/day duloxetine groups compared with placebo, with no significant difference between the two dosages.

In the low- and high-dose groups, 41% of patients experienced a 50% reduction in overall pain, compared with 23% of patients on placebo, Dr. Arnold reported.

Significant improvements over placebo were also seen in the FIQ total, pain, fatigue, and restfulness upon awakening scores; in the mean tender point threshold and number of tender points; in the Clinical Global Impression (CGI) and Patient Global Impression of Improvement (PGI) scores; in other BPI subscale measures of pain severity and interference; and in several quality of life and functional measures.

This study replicated several findings from a previously published trial of 207 fibromyalgia patients that included a small number of men. Dr. Arnold presented the findings of both trials together in a poster at the meeting.

In the earlier study, 104 patients (89% women) were randomized to 120 mg/day of duloxetine, and 103 (89% women) to placebo. Duloxetine patients improved significantly more than did placebo-treated patients on the FIQ total score, but not significantly more on the FIQ pain score (Arthritis Rheum. 2004;50:2974-84).

Duloxetine-treated patients also had significant reductions compared with placebo-treated patients in BPI scores for average pain severity and interference from pain, number of tender points, and FIQ stiffness, as well as several other fibro-myalgia-specific and quality of life measures. The differences were only significant for women, but the number of men was quite small, Dr. Arnold noted.

Major depression was present in approximately 40% of the subjects in the earlier single-dose study and in about one-fourth of the subjects in the two-dose study. In both studies, there were no differences between depressed and nondepressed patients in duloxetine efficacy in alleviating pain and fibromyalgia symptoms, suggesting that these effects are not simply due to an improvement in mood, she noted.

In the first study, duloxetine was significantly more likely than placebo to be associated with side effects including constipation, dry mouth, insomnia, and a small mean increase in heart rate. These were typically mild to moderate in severity. Also in that study, anxiety was reported significantly less often with duloxetine than with placebo.

In the more recent study, nausea, dry mouth, constipation, diarrhea, somnolence, decreased appetite and weight, and a small mean increase in systolic and diastolic blood pressure were among the side effects reported more frequently by duloxetine-treated patients than by those on placebo. These side effects were also generally mild to moderate in severity. In all, the drug was safely administered and well tolerated, Dr. Arnold said.

VANCOUVER, B.C. — Duloxetine is a safe and effective treatment for fibromyalgia symptoms in both depressed and nondepressed women, Lesley Arnold, M.D., reported at the annual meeting of the American Psychosomatic Society.

Duloxetine (Cymbalta) is approved for the treatment of both major depression and diabetic neuropathic pain. The drug's efficacy in treating both pain and depression—which often co-occur in fibromyalgia—is probably due to its dual action as a selective serotonin and norepinephrine reuptake inhibitor, said Dr. Arnold, a psychiatrist who is director of women's health research at the University of Cincinnati.

In one of two 12-week studies funded by Lilly Research Laboratories, a total of 354 adult women who met the American College of Rheumatology's criteria for primary fibromyalgia were randomized to receive 60 mg of duloxetine once a day (118), 60 mg twice daily (116), or placebo (120).

Significant differences in the Brief Pain Inventory (BPI) average 24-hour pain score and the Fibromyalgia Impact Questionnaire (FIQ) were seen within 1 week in both the 60 mg/day and 120 mg/day duloxetine groups compared with placebo, with no significant difference between the two dosages.

In the low- and high-dose groups, 41% of patients experienced a 50% reduction in overall pain, compared with 23% of patients on placebo, Dr. Arnold reported.

Significant improvements over placebo were also seen in the FIQ total, pain, fatigue, and restfulness upon awakening scores; in the mean tender point threshold and number of tender points; in the Clinical Global Impression (CGI) and Patient Global Impression of Improvement (PGI) scores; in other BPI subscale measures of pain severity and interference; and in several quality of life and functional measures.

This study replicated several findings from a previously published trial of 207 fibromyalgia patients that included a small number of men. Dr. Arnold presented the findings of both trials together in a poster at the meeting.

In the earlier study, 104 patients (89% women) were randomized to 120 mg/day of duloxetine, and 103 (89% women) to placebo. Duloxetine patients improved significantly more than did placebo-treated patients on the FIQ total score, but not significantly more on the FIQ pain score (Arthritis Rheum. 2004;50:2974-84).

Duloxetine-treated patients also had significant reductions compared with placebo-treated patients in BPI scores for average pain severity and interference from pain, number of tender points, and FIQ stiffness, as well as several other fibro-myalgia-specific and quality of life measures. The differences were only significant for women, but the number of men was quite small, Dr. Arnold noted.

Major depression was present in approximately 40% of the subjects in the earlier single-dose study and in about one-fourth of the subjects in the two-dose study. In both studies, there were no differences between depressed and nondepressed patients in duloxetine efficacy in alleviating pain and fibromyalgia symptoms, suggesting that these effects are not simply due to an improvement in mood, she noted.

In the first study, duloxetine was significantly more likely than placebo to be associated with side effects including constipation, dry mouth, insomnia, and a small mean increase in heart rate. These were typically mild to moderate in severity. Also in that study, anxiety was reported significantly less often with duloxetine than with placebo.

In the more recent study, nausea, dry mouth, constipation, diarrhea, somnolence, decreased appetite and weight, and a small mean increase in systolic and diastolic blood pressure were among the side effects reported more frequently by duloxetine-treated patients than by those on placebo. These side effects were also generally mild to moderate in severity. In all, the drug was safely administered and well tolerated, Dr. Arnold said.

VANCOUVER, B.C. — Duloxetine is a safe and effective treatment for fibromyalgia symptoms in both depressed and nondepressed women, Lesley Arnold, M.D., reported at the annual meeting of the American Psychosomatic Society.

Duloxetine (Cymbalta) is approved for the treatment of both major depression and diabetic neuropathic pain. The drug's efficacy in treating both pain and depression—which often co-occur in fibromyalgia—is probably due to its dual action as a selective serotonin and norepinephrine reuptake inhibitor, said Dr. Arnold, a psychiatrist who is director of women's health research at the University of Cincinnati.

In one of two 12-week studies funded by Lilly Research Laboratories, a total of 354 adult women who met the American College of Rheumatology's criteria for primary fibromyalgia were randomized to receive 60 mg of duloxetine once a day (118), 60 mg twice daily (116), or placebo (120).

Significant differences in the Brief Pain Inventory (BPI) average 24-hour pain score and the Fibromyalgia Impact Questionnaire (FIQ) were seen within 1 week in both the 60 mg/day and 120 mg/day duloxetine groups compared with placebo, with no significant difference between the two dosages.

In the low- and high-dose groups, 41% of patients experienced a 50% reduction in overall pain, compared with 23% of patients on placebo, Dr. Arnold reported.

Significant improvements over placebo were also seen in the FIQ total, pain, fatigue, and restfulness upon awakening scores; in the mean tender point threshold and number of tender points; in the Clinical Global Impression (CGI) and Patient Global Impression of Improvement (PGI) scores; in other BPI subscale measures of pain severity and interference; and in several quality of life and functional measures.

This study replicated several findings from a previously published trial of 207 fibromyalgia patients that included a small number of men. Dr. Arnold presented the findings of both trials together in a poster at the meeting.

In the earlier study, 104 patients (89% women) were randomized to 120 mg/day of duloxetine, and 103 (89% women) to placebo. Duloxetine patients improved significantly more than did placebo-treated patients on the FIQ total score, but not significantly more on the FIQ pain score (Arthritis Rheum. 2004;50:2974-84).

Duloxetine-treated patients also had significant reductions compared with placebo-treated patients in BPI scores for average pain severity and interference from pain, number of tender points, and FIQ stiffness, as well as several other fibro-myalgia-specific and quality of life measures. The differences were only significant for women, but the number of men was quite small, Dr. Arnold noted.

Major depression was present in approximately 40% of the subjects in the earlier single-dose study and in about one-fourth of the subjects in the two-dose study. In both studies, there were no differences between depressed and nondepressed patients in duloxetine efficacy in alleviating pain and fibromyalgia symptoms, suggesting that these effects are not simply due to an improvement in mood, she noted.

In the first study, duloxetine was significantly more likely than placebo to be associated with side effects including constipation, dry mouth, insomnia, and a small mean increase in heart rate. These were typically mild to moderate in severity. Also in that study, anxiety was reported significantly less often with duloxetine than with placebo.

In the more recent study, nausea, dry mouth, constipation, diarrhea, somnolence, decreased appetite and weight, and a small mean increase in systolic and diastolic blood pressure were among the side effects reported more frequently by duloxetine-treated patients than by those on placebo. These side effects were also generally mild to moderate in severity. In all, the drug was safely administered and well tolerated, Dr. Arnold said.

WASHINGTON — Local anesthetic injected into the lumbar spine, either alone or with a steroid, may help patients avoid surgery for as long as 5 years, according to a study presented by K. Daniel Riew, M.D., and colleagues at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study was a follow-up of a trial they published in the Journal of Bone and Joint Surgery in 2000, in which 55 patients who were surgical candidates were randomly assigned instead to a selective nerve root injection of either bupivacaine alone or bupivacaine and betamethasone. Neither the physician nor the patient knew which was being injected. The injections were administered under fluoroscopic guidance.

At that time, 29 of the 55 patients avoided surgery. Dr. Riew and his colleagues contacted these patients 5 years post injection, and 21 responded. Of those, 9 patients had been injected with only the local anesthetic; and of those patients, 8 had avoided surgery during the intervening years. Twelve of the 21 had been injected with the anesthetic plus steroid, and 9 of those 12 had avoided surgery in the intervening years.

There was no significant difference in surgery avoidance between the patients who had the local anesthetic alone and those receiving the bupivacaine with betamethasone. Dr. Riew said the bupivacaine alone may have had a placebo effect. But, he added, the original nerve root irritation could have healed on its own.

Among the 21 responding patients, 14 had spinal stenosis and 7 had a herniated disc as the initial diagnosis. There was no difference in outcomes between these two groups. All the patients had significant decreases in neurologic symptoms and back pain at 5-year follow-up, said Dr. Riew of Washington University, St Louis.

WASHINGTON — Local anesthetic injected into the lumbar spine, either alone or with a steroid, may help patients avoid surgery for as long as 5 years, according to a study presented by K. Daniel Riew, M.D., and colleagues at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study was a follow-up of a trial they published in the Journal of Bone and Joint Surgery in 2000, in which 55 patients who were surgical candidates were randomly assigned instead to a selective nerve root injection of either bupivacaine alone or bupivacaine and betamethasone. Neither the physician nor the patient knew which was being injected. The injections were administered under fluoroscopic guidance.

At that time, 29 of the 55 patients avoided surgery. Dr. Riew and his colleagues contacted these patients 5 years post injection, and 21 responded. Of those, 9 patients had been injected with only the local anesthetic; and of those patients, 8 had avoided surgery during the intervening years. Twelve of the 21 had been injected with the anesthetic plus steroid, and 9 of those 12 had avoided surgery in the intervening years.

There was no significant difference in surgery avoidance between the patients who had the local anesthetic alone and those receiving the bupivacaine with betamethasone. Dr. Riew said the bupivacaine alone may have had a placebo effect. But, he added, the original nerve root irritation could have healed on its own.

Among the 21 responding patients, 14 had spinal stenosis and 7 had a herniated disc as the initial diagnosis. There was no difference in outcomes between these two groups. All the patients had significant decreases in neurologic symptoms and back pain at 5-year follow-up, said Dr. Riew of Washington University, St Louis.

WASHINGTON — Local anesthetic injected into the lumbar spine, either alone or with a steroid, may help patients avoid surgery for as long as 5 years, according to a study presented by K. Daniel Riew, M.D., and colleagues at the annual meeting of the American Academy of Orthopaedic Surgeons.

The study was a follow-up of a trial they published in the Journal of Bone and Joint Surgery in 2000, in which 55 patients who were surgical candidates were randomly assigned instead to a selective nerve root injection of either bupivacaine alone or bupivacaine and betamethasone. Neither the physician nor the patient knew which was being injected. The injections were administered under fluoroscopic guidance.

At that time, 29 of the 55 patients avoided surgery. Dr. Riew and his colleagues contacted these patients 5 years post injection, and 21 responded. Of those, 9 patients had been injected with only the local anesthetic; and of those patients, 8 had avoided surgery during the intervening years. Twelve of the 21 had been injected with the anesthetic plus steroid, and 9 of those 12 had avoided surgery in the intervening years.

There was no significant difference in surgery avoidance between the patients who had the local anesthetic alone and those receiving the bupivacaine with betamethasone. Dr. Riew said the bupivacaine alone may have had a placebo effect. But, he added, the original nerve root irritation could have healed on its own.

Among the 21 responding patients, 14 had spinal stenosis and 7 had a herniated disc as the initial diagnosis. There was no difference in outcomes between these two groups. All the patients had significant decreases in neurologic symptoms and back pain at 5-year follow-up, said Dr. Riew of Washington University, St Louis.