Rheumatoid Arthritis

PHILADELPHIA — Spinal disk replacement was at least as effective as conventional spinal fusion for treating patients with degenerative disk disease in results from several studies reported at the annual meeting of the North American Spine Society.

Although total disk replacement with a prosthesis is still in development—and so far initial studies have shown it to be no better than spinal fusion—experts believe that arthroplasty has several potential advantages that are fueling interest in this option.

There is the view that both types of repair will play a role. “You can't categorize all patients together. Some patients will need fusion, but for the majority of patients arthroplasty will be better in the long run,” said James J. Yue, M.D., an orthopedic surgeon at Yale University in New Haven, Conn.

Two randomized studies reported at the meeting compared cervical-disk replacement with spinal fusion. One study included 22 patients who had single-level, anterior, cervical diskectomy and fusion with allograft bone and anterior plating, and 24 patients who had single-level, disk replacement using the ProDisc-C prosthesis. Synthes Spine is developing the ProDisc-C for cervical disk replacement and the ProDisc-L for lumbar disk replacement, and the company sponsored the studies with these devices.

Patients were followed for 2 years, and were assessed periodically during follow-up by the neck disability index, short-form-36, a visual analog scale, and by range of motion.

By most of these measures, spinal fusion and arthroplasty showed no significant differences in outcomes at most follow-up assessments. Disk replacement showed a significantly better improvement in neck disability index, compared with fusion after 12 months, but this advantage disappeared during later follow-up, Michael E. Janssen, D.O., and associates reported in a poster at the meeting.

Patients who received the prosthetic disk had less arm pain than the fusion patients after 3, 6, and 12 months of follow-up. Patient satisfaction was significantly higher among the arthroplasty patients, compared with the fusion patients at 6 months after surgery.

No patients in the disk-replacement group had a serious adverse reaction, and there were no device-related issues. Patients who had disk replacement had improved mobility and range of motion following their surgery, said Dr. Janssen, an orthopedic surgeon at the University of Colorado in Denver.

The second cervical study included 21 patients and had a very similar design. After up to 2 years of follow-up, the 11 patients treated by cervical disk replacement had very similar outcomes to the 10 patients who were treated by spinal fusion, Anthony M. Petrizzo, D.O., an orthopedic surgeon at New York University, and his associates reported in a poster.

The two trials comparing lumbar-disk replacement with spinal fusion also had a similar design. One study reported the outcomes of patients with two-level degenerative disk disease. Sixteen patients were randomized to total disk arthroplasty with the ProDisc-L and 8 patients were randomized to circumferential spinal fusion. Another 12 patients with two-level disease were treated with arthroplasty on a nonrandomized basis.

After an average follow-up of 18 months, pain and function were similar in the two groups of patients, who were assessed using a visual analog scale of pain, the Oswestry disability index, the short-form 36, and range of motion tests.

The Oswestry score fell from 70 at baseline to 43 in the arthroplasty patients, and from 64 to 36 in the fusion patients, reported Dr. Petrizzo and his associates in a second poster.

The second comparison study focused on patients with single-level, lumbar-disk disease. Nine patients were randomized to fusion, and 18 were randomized to arthroplasty with a ProDisc-L. An additional 38 patients were treated by arthroplasty in a nonrandomized phase of the study.

During an average follow-up of 1 year, periodic assessments by the same measures used in the two-level study showed no significant differences in response between the two groups, Dr. Petrizzo said during an oral presentation at the meeting.

A fifth study reviewed 22 patients aged 60 or older who received a ProDisc-L to repair lumbar disk disease. The group included 17 patients with single-level disease, 4 with two-level disk degeneration, and 1 patient with three-level disease. Their average age was 63 years.

After a minimum follow-up of 2 years and an average follow-up of more than 34 months, the patients had significant improvements in their Oswestry disability index and pain scores, Dr. Yue said. Significant improvements in the Oswestry score did not appear until patients were followed for at least 1 year. The rate of patient satisfaction was 91%.

Four patients (18%) had complications. Two patients had neurologic complications: one developed a partial foot drop and recovered, the other developed complete foot drop and did not recover. Two other patients had partial implant subsidence. No patients had vascular complications.

“Artificial disc replacement in the elderly is controversial and cannot be generally recommended at this time, especially in patients with circumferential spinal stenosis,” Dr. Yue said.

PHILADELPHIA — Spinal disk replacement was at least as effective as conventional spinal fusion for treating patients with degenerative disk disease in results from several studies reported at the annual meeting of the North American Spine Society.

Although total disk replacement with a prosthesis is still in development—and so far initial studies have shown it to be no better than spinal fusion—experts believe that arthroplasty has several potential advantages that are fueling interest in this option.

There is the view that both types of repair will play a role. “You can't categorize all patients together. Some patients will need fusion, but for the majority of patients arthroplasty will be better in the long run,” said James J. Yue, M.D., an orthopedic surgeon at Yale University in New Haven, Conn.

Two randomized studies reported at the meeting compared cervical-disk replacement with spinal fusion. One study included 22 patients who had single-level, anterior, cervical diskectomy and fusion with allograft bone and anterior plating, and 24 patients who had single-level, disk replacement using the ProDisc-C prosthesis. Synthes Spine is developing the ProDisc-C for cervical disk replacement and the ProDisc-L for lumbar disk replacement, and the company sponsored the studies with these devices.

Patients were followed for 2 years, and were assessed periodically during follow-up by the neck disability index, short-form-36, a visual analog scale, and by range of motion.

By most of these measures, spinal fusion and arthroplasty showed no significant differences in outcomes at most follow-up assessments. Disk replacement showed a significantly better improvement in neck disability index, compared with fusion after 12 months, but this advantage disappeared during later follow-up, Michael E. Janssen, D.O., and associates reported in a poster at the meeting.

Patients who received the prosthetic disk had less arm pain than the fusion patients after 3, 6, and 12 months of follow-up. Patient satisfaction was significantly higher among the arthroplasty patients, compared with the fusion patients at 6 months after surgery.

No patients in the disk-replacement group had a serious adverse reaction, and there were no device-related issues. Patients who had disk replacement had improved mobility and range of motion following their surgery, said Dr. Janssen, an orthopedic surgeon at the University of Colorado in Denver.

The second cervical study included 21 patients and had a very similar design. After up to 2 years of follow-up, the 11 patients treated by cervical disk replacement had very similar outcomes to the 10 patients who were treated by spinal fusion, Anthony M. Petrizzo, D.O., an orthopedic surgeon at New York University, and his associates reported in a poster.

The two trials comparing lumbar-disk replacement with spinal fusion also had a similar design. One study reported the outcomes of patients with two-level degenerative disk disease. Sixteen patients were randomized to total disk arthroplasty with the ProDisc-L and 8 patients were randomized to circumferential spinal fusion. Another 12 patients with two-level disease were treated with arthroplasty on a nonrandomized basis.

After an average follow-up of 18 months, pain and function were similar in the two groups of patients, who were assessed using a visual analog scale of pain, the Oswestry disability index, the short-form 36, and range of motion tests.

The Oswestry score fell from 70 at baseline to 43 in the arthroplasty patients, and from 64 to 36 in the fusion patients, reported Dr. Petrizzo and his associates in a second poster.

The second comparison study focused on patients with single-level, lumbar-disk disease. Nine patients were randomized to fusion, and 18 were randomized to arthroplasty with a ProDisc-L. An additional 38 patients were treated by arthroplasty in a nonrandomized phase of the study.

During an average follow-up of 1 year, periodic assessments by the same measures used in the two-level study showed no significant differences in response between the two groups, Dr. Petrizzo said during an oral presentation at the meeting.

A fifth study reviewed 22 patients aged 60 or older who received a ProDisc-L to repair lumbar disk disease. The group included 17 patients with single-level disease, 4 with two-level disk degeneration, and 1 patient with three-level disease. Their average age was 63 years.

After a minimum follow-up of 2 years and an average follow-up of more than 34 months, the patients had significant improvements in their Oswestry disability index and pain scores, Dr. Yue said. Significant improvements in the Oswestry score did not appear until patients were followed for at least 1 year. The rate of patient satisfaction was 91%.

Four patients (18%) had complications. Two patients had neurologic complications: one developed a partial foot drop and recovered, the other developed complete foot drop and did not recover. Two other patients had partial implant subsidence. No patients had vascular complications.

“Artificial disc replacement in the elderly is controversial and cannot be generally recommended at this time, especially in patients with circumferential spinal stenosis,” Dr. Yue said.

PHILADELPHIA — Spinal disk replacement was at least as effective as conventional spinal fusion for treating patients with degenerative disk disease in results from several studies reported at the annual meeting of the North American Spine Society.

Although total disk replacement with a prosthesis is still in development—and so far initial studies have shown it to be no better than spinal fusion—experts believe that arthroplasty has several potential advantages that are fueling interest in this option.

There is the view that both types of repair will play a role. “You can't categorize all patients together. Some patients will need fusion, but for the majority of patients arthroplasty will be better in the long run,” said James J. Yue, M.D., an orthopedic surgeon at Yale University in New Haven, Conn.

Two randomized studies reported at the meeting compared cervical-disk replacement with spinal fusion. One study included 22 patients who had single-level, anterior, cervical diskectomy and fusion with allograft bone and anterior plating, and 24 patients who had single-level, disk replacement using the ProDisc-C prosthesis. Synthes Spine is developing the ProDisc-C for cervical disk replacement and the ProDisc-L for lumbar disk replacement, and the company sponsored the studies with these devices.

Patients were followed for 2 years, and were assessed periodically during follow-up by the neck disability index, short-form-36, a visual analog scale, and by range of motion.

By most of these measures, spinal fusion and arthroplasty showed no significant differences in outcomes at most follow-up assessments. Disk replacement showed a significantly better improvement in neck disability index, compared with fusion after 12 months, but this advantage disappeared during later follow-up, Michael E. Janssen, D.O., and associates reported in a poster at the meeting.

Patients who received the prosthetic disk had less arm pain than the fusion patients after 3, 6, and 12 months of follow-up. Patient satisfaction was significantly higher among the arthroplasty patients, compared with the fusion patients at 6 months after surgery.

No patients in the disk-replacement group had a serious adverse reaction, and there were no device-related issues. Patients who had disk replacement had improved mobility and range of motion following their surgery, said Dr. Janssen, an orthopedic surgeon at the University of Colorado in Denver.

The second cervical study included 21 patients and had a very similar design. After up to 2 years of follow-up, the 11 patients treated by cervical disk replacement had very similar outcomes to the 10 patients who were treated by spinal fusion, Anthony M. Petrizzo, D.O., an orthopedic surgeon at New York University, and his associates reported in a poster.

The two trials comparing lumbar-disk replacement with spinal fusion also had a similar design. One study reported the outcomes of patients with two-level degenerative disk disease. Sixteen patients were randomized to total disk arthroplasty with the ProDisc-L and 8 patients were randomized to circumferential spinal fusion. Another 12 patients with two-level disease were treated with arthroplasty on a nonrandomized basis.

After an average follow-up of 18 months, pain and function were similar in the two groups of patients, who were assessed using a visual analog scale of pain, the Oswestry disability index, the short-form 36, and range of motion tests.

The Oswestry score fell from 70 at baseline to 43 in the arthroplasty patients, and from 64 to 36 in the fusion patients, reported Dr. Petrizzo and his associates in a second poster.

The second comparison study focused on patients with single-level, lumbar-disk disease. Nine patients were randomized to fusion, and 18 were randomized to arthroplasty with a ProDisc-L. An additional 38 patients were treated by arthroplasty in a nonrandomized phase of the study.

During an average follow-up of 1 year, periodic assessments by the same measures used in the two-level study showed no significant differences in response between the two groups, Dr. Petrizzo said during an oral presentation at the meeting.

A fifth study reviewed 22 patients aged 60 or older who received a ProDisc-L to repair lumbar disk disease. The group included 17 patients with single-level disease, 4 with two-level disk degeneration, and 1 patient with three-level disease. Their average age was 63 years.

After a minimum follow-up of 2 years and an average follow-up of more than 34 months, the patients had significant improvements in their Oswestry disability index and pain scores, Dr. Yue said. Significant improvements in the Oswestry score did not appear until patients were followed for at least 1 year. The rate of patient satisfaction was 91%.

Four patients (18%) had complications. Two patients had neurologic complications: one developed a partial foot drop and recovered, the other developed complete foot drop and did not recover. Two other patients had partial implant subsidence. No patients had vascular complications.

“Artificial disc replacement in the elderly is controversial and cannot be generally recommended at this time, especially in patients with circumferential spinal stenosis,” Dr. Yue said.

DENVER — Moderate-dose radiotherapy is highly effective in achieving sustained remission in patients with high-risk pigmented villonodular synovitis, Brian O'Sullivan, M.B., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Through 20 years of experience in managing this proliferative disease, he has concluded that the best approach is surgical gross total removal of the lesion followed by radiotherapy (RT). But when surgery is likely to compromise function, RT alone will achieve control of gross disease, according to Dr. O'Sullivan, a radiation oncologist at Princess Margaret Hospital and professor of radiation oncology at the University of Toronto.

Pigmented villonodular synovitis (PVSN) is a rare monoarticular proliferative process originating in synovial membranes. Although it can affect any mobile joint, the knee is the most common site. Lesions can also arise in bursae or tendon sheaths. PVSN can be a destructive process involving invasion of cartilage, bone, and adjacent tissues, with resultant major loss of function and, occasionally, amputation. Its treatment poses technical challenges, especially in patients with large circumferential lesions of the knee, for whom the goal is to deliver enough RT to control the disease while sparing some of the often limited quantity of normal tissue.

“I get more calls about PVSN than any other disease I treat,” the physician said.

The classic PVSN scenario involves a swollen joint with episodes of painful acute swelling related to acute hemarthrosis. “It often mimics the type of joint a hemophiliac patient has,” said Dr. O'Sullivan.

PVSN comes in two forms. Nodular PVSN consists of a pedunculated lesion surrounded by normal synovium. The diffuse form is far more problematic, with recurrence rates of 50%–90% quoted in various series. The arthroscopic appearance of diffuse PVSN typically features a shaggy “large beard” villous proliferation with a thickened, overgrown synovium, often accompanied by bony scalloping or erosion.

Dr. O'Sullivan presented a series of 41 patients with PVSN who were prospectively followed for a mean of 77 months after RT. Of these, 23 presented with recurrent disease for which they had undergone a mean of two prior surgical procedures. The other 18 had what he described as “primary disease of prodigious proportions.” The lesion originated in the knee in 15 patients, and in another joint in 21 others; in 5 patients the disease arose in a periarticular tendon sheath. All patients had the poorer prognosis (diffuse) type of PVSN. All but one had both intra- and extraarticular disease. Three-quarters of the lesions were larger than 5 cm, and 17 were larger than 10 cm.

The RT regimen has evolved over time. Dr. O'Sullivan has settled on a dose of 40 Gy administered in 20 fractions over 3 weeks as optimal. This is supplemented by a final 8-Gy boost to the area of fullest disease. Arthroscopic surgery port sites also get a bolus, because he has observed that PVSN preferentially spreads there.

At a mean of 77 months, 40 of 41 patients remain in good local control as defined either by an absence of clinical and imaging evidence of disease in patients free of overt disease at the time of RT, or by stable disease on serial follow-up imaging studies. One patient developed lesion growth starting 4 years post RT. Functional status was deemed good in 31 patients and adequate in 5. Both patients whose functional status was rated as poor had significant preexisting bone involvement. There have been no RT-induced neoplasias.

In response to audience questions, Dr. O'Sullivan said he often holds off on RT until he can evaluate the tempo of the disease. But he tends to intervene early in large progressive knee and hip lesions. “The problem is, if you let this disease persist and it continues to grow, it will destroy the joint,” he warned.

This excised synovium demonstrates the fronds and nodules that are typical of pigmented villonodular synovitis. ©Saunders 2005. Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7E

DENVER — Moderate-dose radiotherapy is highly effective in achieving sustained remission in patients with high-risk pigmented villonodular synovitis, Brian O'Sullivan, M.B., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Through 20 years of experience in managing this proliferative disease, he has concluded that the best approach is surgical gross total removal of the lesion followed by radiotherapy (RT). But when surgery is likely to compromise function, RT alone will achieve control of gross disease, according to Dr. O'Sullivan, a radiation oncologist at Princess Margaret Hospital and professor of radiation oncology at the University of Toronto.

Pigmented villonodular synovitis (PVSN) is a rare monoarticular proliferative process originating in synovial membranes. Although it can affect any mobile joint, the knee is the most common site. Lesions can also arise in bursae or tendon sheaths. PVSN can be a destructive process involving invasion of cartilage, bone, and adjacent tissues, with resultant major loss of function and, occasionally, amputation. Its treatment poses technical challenges, especially in patients with large circumferential lesions of the knee, for whom the goal is to deliver enough RT to control the disease while sparing some of the often limited quantity of normal tissue.

“I get more calls about PVSN than any other disease I treat,” the physician said.

The classic PVSN scenario involves a swollen joint with episodes of painful acute swelling related to acute hemarthrosis. “It often mimics the type of joint a hemophiliac patient has,” said Dr. O'Sullivan.

PVSN comes in two forms. Nodular PVSN consists of a pedunculated lesion surrounded by normal synovium. The diffuse form is far more problematic, with recurrence rates of 50%–90% quoted in various series. The arthroscopic appearance of diffuse PVSN typically features a shaggy “large beard” villous proliferation with a thickened, overgrown synovium, often accompanied by bony scalloping or erosion.

Dr. O'Sullivan presented a series of 41 patients with PVSN who were prospectively followed for a mean of 77 months after RT. Of these, 23 presented with recurrent disease for which they had undergone a mean of two prior surgical procedures. The other 18 had what he described as “primary disease of prodigious proportions.” The lesion originated in the knee in 15 patients, and in another joint in 21 others; in 5 patients the disease arose in a periarticular tendon sheath. All patients had the poorer prognosis (diffuse) type of PVSN. All but one had both intra- and extraarticular disease. Three-quarters of the lesions were larger than 5 cm, and 17 were larger than 10 cm.

The RT regimen has evolved over time. Dr. O'Sullivan has settled on a dose of 40 Gy administered in 20 fractions over 3 weeks as optimal. This is supplemented by a final 8-Gy boost to the area of fullest disease. Arthroscopic surgery port sites also get a bolus, because he has observed that PVSN preferentially spreads there.

At a mean of 77 months, 40 of 41 patients remain in good local control as defined either by an absence of clinical and imaging evidence of disease in patients free of overt disease at the time of RT, or by stable disease on serial follow-up imaging studies. One patient developed lesion growth starting 4 years post RT. Functional status was deemed good in 31 patients and adequate in 5. Both patients whose functional status was rated as poor had significant preexisting bone involvement. There have been no RT-induced neoplasias.

In response to audience questions, Dr. O'Sullivan said he often holds off on RT until he can evaluate the tempo of the disease. But he tends to intervene early in large progressive knee and hip lesions. “The problem is, if you let this disease persist and it continues to grow, it will destroy the joint,” he warned.

This excised synovium demonstrates the fronds and nodules that are typical of pigmented villonodular synovitis. ©Saunders 2005. Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7E

DENVER — Moderate-dose radiotherapy is highly effective in achieving sustained remission in patients with high-risk pigmented villonodular synovitis, Brian O'Sullivan, M.B., said at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

Through 20 years of experience in managing this proliferative disease, he has concluded that the best approach is surgical gross total removal of the lesion followed by radiotherapy (RT). But when surgery is likely to compromise function, RT alone will achieve control of gross disease, according to Dr. O'Sullivan, a radiation oncologist at Princess Margaret Hospital and professor of radiation oncology at the University of Toronto.

Pigmented villonodular synovitis (PVSN) is a rare monoarticular proliferative process originating in synovial membranes. Although it can affect any mobile joint, the knee is the most common site. Lesions can also arise in bursae or tendon sheaths. PVSN can be a destructive process involving invasion of cartilage, bone, and adjacent tissues, with resultant major loss of function and, occasionally, amputation. Its treatment poses technical challenges, especially in patients with large circumferential lesions of the knee, for whom the goal is to deliver enough RT to control the disease while sparing some of the often limited quantity of normal tissue.

“I get more calls about PVSN than any other disease I treat,” the physician said.

The classic PVSN scenario involves a swollen joint with episodes of painful acute swelling related to acute hemarthrosis. “It often mimics the type of joint a hemophiliac patient has,” said Dr. O'Sullivan.

PVSN comes in two forms. Nodular PVSN consists of a pedunculated lesion surrounded by normal synovium. The diffuse form is far more problematic, with recurrence rates of 50%–90% quoted in various series. The arthroscopic appearance of diffuse PVSN typically features a shaggy “large beard” villous proliferation with a thickened, overgrown synovium, often accompanied by bony scalloping or erosion.

Dr. O'Sullivan presented a series of 41 patients with PVSN who were prospectively followed for a mean of 77 months after RT. Of these, 23 presented with recurrent disease for which they had undergone a mean of two prior surgical procedures. The other 18 had what he described as “primary disease of prodigious proportions.” The lesion originated in the knee in 15 patients, and in another joint in 21 others; in 5 patients the disease arose in a periarticular tendon sheath. All patients had the poorer prognosis (diffuse) type of PVSN. All but one had both intra- and extraarticular disease. Three-quarters of the lesions were larger than 5 cm, and 17 were larger than 10 cm.

The RT regimen has evolved over time. Dr. O'Sullivan has settled on a dose of 40 Gy administered in 20 fractions over 3 weeks as optimal. This is supplemented by a final 8-Gy boost to the area of fullest disease. Arthroscopic surgery port sites also get a bolus, because he has observed that PVSN preferentially spreads there.

At a mean of 77 months, 40 of 41 patients remain in good local control as defined either by an absence of clinical and imaging evidence of disease in patients free of overt disease at the time of RT, or by stable disease on serial follow-up imaging studies. One patient developed lesion growth starting 4 years post RT. Functional status was deemed good in 31 patients and adequate in 5. Both patients whose functional status was rated as poor had significant preexisting bone involvement. There have been no RT-induced neoplasias.

In response to audience questions, Dr. O'Sullivan said he often holds off on RT until he can evaluate the tempo of the disease. But he tends to intervene early in large progressive knee and hip lesions. “The problem is, if you let this disease persist and it continues to grow, it will destroy the joint,” he warned.

This excised synovium demonstrates the fronds and nodules that are typical of pigmented villonodular synovitis. ©Saunders 2005. Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7E

PHILADELPHIA — Patients do “quite well” both mentally and physically 5 years following lumbar diskectomy, based on follow-up of 53 patients.

Lumbar diskectomy has become one of the most common spinal, surgical procedures in the United States, William C. Welch, M.D., said at the annual meeting of the North American Spine Society.

“Remarkably, this is the first study to show positive, 5-year outcomes on a number of important biopsychosocial variables,” said the chief of neurologic surgery and spine services at the University of Pittsburgh.

The study included a sample of patients aged 18 or older who had a first diskectomy done at any of eight medical centers in the United States during January 1997-March 1999. Questionnaires and surveys were sent to each patient.

Overall, the scores showed the patients were doing well with little disability and were satisfied with their outcomes. None of the questionnaire results were significantly different from normative values, said Dr. Welch, professor of neurologic and orthopedic surgery at the university.

For example, the average physical component scale score on the Short Form-12 questionnaire was 42.47, and the mental component score was 53.47, both in the normal range. The average treatment helpfulness questionnaire score was 49.8 on a scale where 50 indicates good, overall satisfaction. The average Pain Disability Questionnaire score was 21.1, in a range where 0 indicates no problem and 150 indicates the greatest severity.

The rate of repeat surgery at the same disk level was 9.8%, a rate that's “fairly high,” Dr. Welch said.

PHILADELPHIA — Patients do “quite well” both mentally and physically 5 years following lumbar diskectomy, based on follow-up of 53 patients.

Lumbar diskectomy has become one of the most common spinal, surgical procedures in the United States, William C. Welch, M.D., said at the annual meeting of the North American Spine Society.

“Remarkably, this is the first study to show positive, 5-year outcomes on a number of important biopsychosocial variables,” said the chief of neurologic surgery and spine services at the University of Pittsburgh.

The study included a sample of patients aged 18 or older who had a first diskectomy done at any of eight medical centers in the United States during January 1997-March 1999. Questionnaires and surveys were sent to each patient.

Overall, the scores showed the patients were doing well with little disability and were satisfied with their outcomes. None of the questionnaire results were significantly different from normative values, said Dr. Welch, professor of neurologic and orthopedic surgery at the university.

For example, the average physical component scale score on the Short Form-12 questionnaire was 42.47, and the mental component score was 53.47, both in the normal range. The average treatment helpfulness questionnaire score was 49.8 on a scale where 50 indicates good, overall satisfaction. The average Pain Disability Questionnaire score was 21.1, in a range where 0 indicates no problem and 150 indicates the greatest severity.

The rate of repeat surgery at the same disk level was 9.8%, a rate that's “fairly high,” Dr. Welch said.

PHILADELPHIA — Patients do “quite well” both mentally and physically 5 years following lumbar diskectomy, based on follow-up of 53 patients.

Lumbar diskectomy has become one of the most common spinal, surgical procedures in the United States, William C. Welch, M.D., said at the annual meeting of the North American Spine Society.

“Remarkably, this is the first study to show positive, 5-year outcomes on a number of important biopsychosocial variables,” said the chief of neurologic surgery and spine services at the University of Pittsburgh.

The study included a sample of patients aged 18 or older who had a first diskectomy done at any of eight medical centers in the United States during January 1997-March 1999. Questionnaires and surveys were sent to each patient.

Overall, the scores showed the patients were doing well with little disability and were satisfied with their outcomes. None of the questionnaire results were significantly different from normative values, said Dr. Welch, professor of neurologic and orthopedic surgery at the university.

For example, the average physical component scale score on the Short Form-12 questionnaire was 42.47, and the mental component score was 53.47, both in the normal range. The average treatment helpfulness questionnaire score was 49.8 on a scale where 50 indicates good, overall satisfaction. The average Pain Disability Questionnaire score was 21.1, in a range where 0 indicates no problem and 150 indicates the greatest severity.

The rate of repeat surgery at the same disk level was 9.8%, a rate that's “fairly high,” Dr. Welch said.

PHILADELPHIA — Recombinant human-bone morphogenic protein-2 was more effective than an autologous iliac crest bone graft for facilitating lumbar fusion in a randomized study with 47 patients.

The results of the study showed “several improvements in lumbar fusion procedures provided by the use of rhBMP-2 as a replacement for an autologous iliac crest bone graft,” J. Kenneth Burkus, M.D., and his associates said in a poster at the annual meeting of the North American Spine Society.

The study was sponsored by Medtronic Sofamor Danek. Dr. Burkus is a consultant to the company, which makes rhMBP-2 under the trade name Infuse Bone Graft. This material has not received approval from the Food and Drug Administration.

The study enrolled patients with symptomatic, single-level lumbar spondylosis. The patients underwent anterior lumbar discectomy and interbody fusion using threaded, cortical allografts. The surgeries were done at one of five participating centers. Patients were randomized, with 23 treated with an autologous, iliac-crest bone graft and 24 treated with rhBMP-2 on a collagen sponge carrier. The demographic profile and medical histories of patients in the two groups were similar.

After 48 months of follow-up, patients treated with rhBMP-2 consistently had better clinical outcomes than the controls.

The Oswestry low-back pain disability questionnaire score improved by an average of 23.9 points among patients in the rhBMP-2 group vs. an average drop of 18.5 points among the control patients, reported Dr. Burkus, an orthopedic surgeon at the Hughston Clinic in Columbus, Ga.

The physical component score of the short form (SF)-36 improved by a mean of 10.3 points among patients treated with rhBMP-2 and by 4.4 points in those who received an iliac-crest graft.

After 48 months, 78% of patients in the rhBMP-2 group were working, compared with 41% in the control group. And 94% of patients in the rhBMP-2 group showed evidence of lumbar interbody fusion after 48 months vs. 71% of the control patients.

There was no clinical or radiologic evidence that any patient had degeneration in a segment adjacent to the one that was fused, he reported in the poster.

PHILADELPHIA — Recombinant human-bone morphogenic protein-2 was more effective than an autologous iliac crest bone graft for facilitating lumbar fusion in a randomized study with 47 patients.

The results of the study showed “several improvements in lumbar fusion procedures provided by the use of rhBMP-2 as a replacement for an autologous iliac crest bone graft,” J. Kenneth Burkus, M.D., and his associates said in a poster at the annual meeting of the North American Spine Society.

The study was sponsored by Medtronic Sofamor Danek. Dr. Burkus is a consultant to the company, which makes rhMBP-2 under the trade name Infuse Bone Graft. This material has not received approval from the Food and Drug Administration.

The study enrolled patients with symptomatic, single-level lumbar spondylosis. The patients underwent anterior lumbar discectomy and interbody fusion using threaded, cortical allografts. The surgeries were done at one of five participating centers. Patients were randomized, with 23 treated with an autologous, iliac-crest bone graft and 24 treated with rhBMP-2 on a collagen sponge carrier. The demographic profile and medical histories of patients in the two groups were similar.

After 48 months of follow-up, patients treated with rhBMP-2 consistently had better clinical outcomes than the controls.

The Oswestry low-back pain disability questionnaire score improved by an average of 23.9 points among patients in the rhBMP-2 group vs. an average drop of 18.5 points among the control patients, reported Dr. Burkus, an orthopedic surgeon at the Hughston Clinic in Columbus, Ga.

The physical component score of the short form (SF)-36 improved by a mean of 10.3 points among patients treated with rhBMP-2 and by 4.4 points in those who received an iliac-crest graft.

After 48 months, 78% of patients in the rhBMP-2 group were working, compared with 41% in the control group. And 94% of patients in the rhBMP-2 group showed evidence of lumbar interbody fusion after 48 months vs. 71% of the control patients.

There was no clinical or radiologic evidence that any patient had degeneration in a segment adjacent to the one that was fused, he reported in the poster.

PHILADELPHIA — Recombinant human-bone morphogenic protein-2 was more effective than an autologous iliac crest bone graft for facilitating lumbar fusion in a randomized study with 47 patients.

The results of the study showed “several improvements in lumbar fusion procedures provided by the use of rhBMP-2 as a replacement for an autologous iliac crest bone graft,” J. Kenneth Burkus, M.D., and his associates said in a poster at the annual meeting of the North American Spine Society.

The study was sponsored by Medtronic Sofamor Danek. Dr. Burkus is a consultant to the company, which makes rhMBP-2 under the trade name Infuse Bone Graft. This material has not received approval from the Food and Drug Administration.

The study enrolled patients with symptomatic, single-level lumbar spondylosis. The patients underwent anterior lumbar discectomy and interbody fusion using threaded, cortical allografts. The surgeries were done at one of five participating centers. Patients were randomized, with 23 treated with an autologous, iliac-crest bone graft and 24 treated with rhBMP-2 on a collagen sponge carrier. The demographic profile and medical histories of patients in the two groups were similar.

After 48 months of follow-up, patients treated with rhBMP-2 consistently had better clinical outcomes than the controls.

The Oswestry low-back pain disability questionnaire score improved by an average of 23.9 points among patients in the rhBMP-2 group vs. an average drop of 18.5 points among the control patients, reported Dr. Burkus, an orthopedic surgeon at the Hughston Clinic in Columbus, Ga.

The physical component score of the short form (SF)-36 improved by a mean of 10.3 points among patients treated with rhBMP-2 and by 4.4 points in those who received an iliac-crest graft.

After 48 months, 78% of patients in the rhBMP-2 group were working, compared with 41% in the control group. And 94% of patients in the rhBMP-2 group showed evidence of lumbar interbody fusion after 48 months vs. 71% of the control patients.

There was no clinical or radiologic evidence that any patient had degeneration in a segment adjacent to the one that was fused, he reported in the poster.

SAN ANTONIO — A simple treatment for basilar thumb arthritis that requires minimal convalescence may be just as effective as more complex procedures requiring a longer healing period, Nicholas J. Meyer, M.D., said at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

The procedure consists of a trapezium excision to stabilize the first and second metacarpal bases, followed by packing of the trapezial space with Gelfoam and suture suspensionplasty, explained Dr. Meyer of St. Croix Orthopaedics, Stillwater, Minn.

Dr. Meyer and his associates treated 42 patients with the procedure. The outcomes were evaluated using the disabilities of the arm, shoulder, and hand (DASH) survey, measures of grip and pinch strength, and radiographic assessment.

Radiographic follow-up showed that shortening of the metacarpal-scaphoid space occurred at an average of 4 mm within 2 months after surgery. Age, sex, or other diagnoses appeared to have no effect on this result.

Approximately 90% of patients reported satisfaction with their results, and 86% said they would repeat the treatment and recommend it to a friend. Ten percent were neutral or expressed dissatisfaction with the outcome.

“The results in this cohort of patients show satisfaction rates similar to other more complex procedures,” Dr. Meyer noted.

However, he said that a direct comparison study may be necessary to compare this procedure with trapeziectomy and the more complex procedures, such as ligament reconstruction and tendon interposition.

SAN ANTONIO — A simple treatment for basilar thumb arthritis that requires minimal convalescence may be just as effective as more complex procedures requiring a longer healing period, Nicholas J. Meyer, M.D., said at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

The procedure consists of a trapezium excision to stabilize the first and second metacarpal bases, followed by packing of the trapezial space with Gelfoam and suture suspensionplasty, explained Dr. Meyer of St. Croix Orthopaedics, Stillwater, Minn.

Dr. Meyer and his associates treated 42 patients with the procedure. The outcomes were evaluated using the disabilities of the arm, shoulder, and hand (DASH) survey, measures of grip and pinch strength, and radiographic assessment.

Radiographic follow-up showed that shortening of the metacarpal-scaphoid space occurred at an average of 4 mm within 2 months after surgery. Age, sex, or other diagnoses appeared to have no effect on this result.

Approximately 90% of patients reported satisfaction with their results, and 86% said they would repeat the treatment and recommend it to a friend. Ten percent were neutral or expressed dissatisfaction with the outcome.

“The results in this cohort of patients show satisfaction rates similar to other more complex procedures,” Dr. Meyer noted.

However, he said that a direct comparison study may be necessary to compare this procedure with trapeziectomy and the more complex procedures, such as ligament reconstruction and tendon interposition.

SAN ANTONIO — A simple treatment for basilar thumb arthritis that requires minimal convalescence may be just as effective as more complex procedures requiring a longer healing period, Nicholas J. Meyer, M.D., said at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

The procedure consists of a trapezium excision to stabilize the first and second metacarpal bases, followed by packing of the trapezial space with Gelfoam and suture suspensionplasty, explained Dr. Meyer of St. Croix Orthopaedics, Stillwater, Minn.

Dr. Meyer and his associates treated 42 patients with the procedure. The outcomes were evaluated using the disabilities of the arm, shoulder, and hand (DASH) survey, measures of grip and pinch strength, and radiographic assessment.

Radiographic follow-up showed that shortening of the metacarpal-scaphoid space occurred at an average of 4 mm within 2 months after surgery. Age, sex, or other diagnoses appeared to have no effect on this result.

Approximately 90% of patients reported satisfaction with their results, and 86% said they would repeat the treatment and recommend it to a friend. Ten percent were neutral or expressed dissatisfaction with the outcome.

“The results in this cohort of patients show satisfaction rates similar to other more complex procedures,” Dr. Meyer noted.

However, he said that a direct comparison study may be necessary to compare this procedure with trapeziectomy and the more complex procedures, such as ligament reconstruction and tendon interposition.

SAN ANTONIO — Injections of a hyaluronic acid derivative provide a safer and more effective alternative to corticosteroids for nonoperative treatment of trapeziometacarpal arthritis, according to a report presented at a joint annual meeting of the American Society for Surgery of the Hand and American Society of Hand Therapists.

Long used to treat symptoms of knee osteoarthritis, injections of the hyaluronic acid derivative Synvisc (hylan) were compared with injections of corticosteroid and placebo for basal-joint arthritis in a study led by Melvin P. Rosenwasser, M.D., and associates from Columbia University Medical School, New York.

Sixty patients with basal-joint arthritis were randomized to three groups: two intraarticular injections of Synvisc at weekly intervals, one placebo injection followed by one corticosteroid injection 1 week later, or two saline injections 1 week apart.

Patients were evaluated at 2 weeks, 1 month, 3 months, and 6 months and were assessed using patient satisfaction surveys, including the visual analog scores for pain (VAS); disabilities of the arm, shoulder, and hand (DASH) scores; and physical examinations testing thumb range of motion (ROM), grip strength, and pinch strength.

The majority of patients were postmenopausal women, with an average age of 63 years, and the dominant hand was affected. VAS results showed statistically significant improvement in the placebo and steroid groups at 1 month, but not at 6 months, compared with baseline. Significant pain relief in the hylan group occurred at 6 months, but not at 1 month.

At 1-month follow up, symptoms had improved in 50% of the placebo group, 68% of the steroid group, and 44% of the hylan group.

At 6 months, symptoms had improved by 68% in the hylan group, 58% in the steroid group, and 47% in the placebo group.

Benefits with regard to pain, grip and pinch strength, and range of motion were similar in all three groups until the 26th week, when hylan's benefits appeared more significant, said Dr. Rosenwasser, noting there were no adverse effects from treatment in any of the groups.

SAN ANTONIO — Injections of a hyaluronic acid derivative provide a safer and more effective alternative to corticosteroids for nonoperative treatment of trapeziometacarpal arthritis, according to a report presented at a joint annual meeting of the American Society for Surgery of the Hand and American Society of Hand Therapists.

Long used to treat symptoms of knee osteoarthritis, injections of the hyaluronic acid derivative Synvisc (hylan) were compared with injections of corticosteroid and placebo for basal-joint arthritis in a study led by Melvin P. Rosenwasser, M.D., and associates from Columbia University Medical School, New York.

Sixty patients with basal-joint arthritis were randomized to three groups: two intraarticular injections of Synvisc at weekly intervals, one placebo injection followed by one corticosteroid injection 1 week later, or two saline injections 1 week apart.

Patients were evaluated at 2 weeks, 1 month, 3 months, and 6 months and were assessed using patient satisfaction surveys, including the visual analog scores for pain (VAS); disabilities of the arm, shoulder, and hand (DASH) scores; and physical examinations testing thumb range of motion (ROM), grip strength, and pinch strength.

The majority of patients were postmenopausal women, with an average age of 63 years, and the dominant hand was affected. VAS results showed statistically significant improvement in the placebo and steroid groups at 1 month, but not at 6 months, compared with baseline. Significant pain relief in the hylan group occurred at 6 months, but not at 1 month.

At 1-month follow up, symptoms had improved in 50% of the placebo group, 68% of the steroid group, and 44% of the hylan group.

At 6 months, symptoms had improved by 68% in the hylan group, 58% in the steroid group, and 47% in the placebo group.

Benefits with regard to pain, grip and pinch strength, and range of motion were similar in all three groups until the 26th week, when hylan's benefits appeared more significant, said Dr. Rosenwasser, noting there were no adverse effects from treatment in any of the groups.

SAN ANTONIO — Injections of a hyaluronic acid derivative provide a safer and more effective alternative to corticosteroids for nonoperative treatment of trapeziometacarpal arthritis, according to a report presented at a joint annual meeting of the American Society for Surgery of the Hand and American Society of Hand Therapists.

Long used to treat symptoms of knee osteoarthritis, injections of the hyaluronic acid derivative Synvisc (hylan) were compared with injections of corticosteroid and placebo for basal-joint arthritis in a study led by Melvin P. Rosenwasser, M.D., and associates from Columbia University Medical School, New York.

Sixty patients with basal-joint arthritis were randomized to three groups: two intraarticular injections of Synvisc at weekly intervals, one placebo injection followed by one corticosteroid injection 1 week later, or two saline injections 1 week apart.

Patients were evaluated at 2 weeks, 1 month, 3 months, and 6 months and were assessed using patient satisfaction surveys, including the visual analog scores for pain (VAS); disabilities of the arm, shoulder, and hand (DASH) scores; and physical examinations testing thumb range of motion (ROM), grip strength, and pinch strength.

The majority of patients were postmenopausal women, with an average age of 63 years, and the dominant hand was affected. VAS results showed statistically significant improvement in the placebo and steroid groups at 1 month, but not at 6 months, compared with baseline. Significant pain relief in the hylan group occurred at 6 months, but not at 1 month.

At 1-month follow up, symptoms had improved in 50% of the placebo group, 68% of the steroid group, and 44% of the hylan group.

At 6 months, symptoms had improved by 68% in the hylan group, 58% in the steroid group, and 47% in the placebo group.

Benefits with regard to pain, grip and pinch strength, and range of motion were similar in all three groups until the 26th week, when hylan's benefits appeared more significant, said Dr. Rosenwasser, noting there were no adverse effects from treatment in any of the groups.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

Low doses of prednisolone given for 2 years along with disease-modifying antirheumatic drug therapy substantially and safely reduced radiographic progression of rheumatoid arthritis in patients with early, active disease, according to the results of two new randomized studies.

Investigators of the two studies say that their findings support the use of low-dose daily prednisolone as a low-risk adjunct to DMARDs in patients with early RA.

One study compared the addition of 7.5 mg/day prednisolone to initial DMARD therapy (either methotrexate or sulfasalazine) with DMARD therapy alone in 250 patients recruited in six centers throughout Sweden from 1995 to 1999. The patients had had RA for 1 year or less.

Patients in the second study were randomized to receive placebo or an even smaller dose of prednisolone—5 mg/day—in addition to therapy with either gold sodium thiomalate or methotrexate.

The 103 patients who completed this study had a slightly longer disease duration—2 years or less—when they started treatment.

They were enrolled in the study between 1993 and 1995 in 20 clinics and private practices in Germany, Austria, and Switzerland.

The two studies were similar in that the choice of DMARD therapy was left to the treating physician. There were no significant differences, however, in the types and dosages of DMARD therapy between the patients who were randomized to receive prednisolone and those who received placebo or no prednisolone.

Concomitant treatment with NSAIDs and osteoporosis prophylaxis with calcium was allowed in both studies, and patients with any history of treatment with DMARDs or glucocorticoids were excluded. Joint destruction was monitored in both studies primarily through radiographs of the hands and feet.

The Swedish investigators used the Sharp score as modified by van der Heijde to assess radiographs at baseline and after 1 and 2 years of treatment. The change in the total score, they found, was significantly lower after 1 and 2 years in the prednisolone group than in the no-prednisolone group. (At 2 years, for instance, the median interquartile change in total score was 1.8 and 3.5, respectively.)

The erosion score also changed significantly less in the prednisolone group, and joint space narrowing was retarded, though to a lesser extent than erosion.

Patients in the prednisolone group also had significantly fewer newly eroded joints after 2 years, as well as improved physical functioning and significantly higher rates of disease remission (51% vs. 39% in the no-prednisolone group at 1 year, and 56% vs. 33% at 2 years), reported Björn Svensson, M.D., Ph.D., of the University of Lund (Sweden), and his associates (Arthritis Rheum. 2005:52;3360–70).

Investigators in the multicountry study used two scoring systems—the Ratingen score and the modified Sharp/van der Heijde score—to assess radiographs taken at 6 months, 1 year, and 2 years after the start of treatment.

Their results were similar: Increases in the Ratingen score, the Sharp score for erosion, and the total Sharp score were significantly less at each point in time in patients taking prednisolone than in patients taking placebo. Changes in the score for joint space narrowing were significantly different only at 6 months.

In addition, clinical and functional outcomes, as well as rates of disease remission, tended to be better—though not to the level of statistical significance—in the prednisolone group, reported Siegfried Wassenberg, M.D., of Evangelisches Fachkrankenhaus Ratingen (Germany), and his associates (Arthritis Rheum. 2005:52;3371–80).

Some side effects such as weight gain (four patients), hypertension (six), Cushing's syndrome (five), and glaucoma (three) were reported only among patients taking prednisolone.

In the Swedish study, the frequency of adverse events was small, investigators said. And in both studies, prednisolone had little or no impact on bone loss.

“It remains to be seen whether dosages lower than 5 mg provide the same benefit with even fewer side effects and whether the same effect can be produced in patients with more advanced disease,” Dr. Wassenberg and associates said.

A third tumor necrosis factor inhibitor has been added to the arsenal of drugs approved for treating psoriatic arthritis.

Adalimumab, a fully human, anti-TNF monoclonal antibody, significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active psoriatic arthritis, according to the findings of multicenter study.

Adalimumab and infliximab have been approved by the Food and Drug Administration for the treatment of psoriatic arthritis (PsA), but not for the dermatologic treatment of psoriasis in the absence of joint involvement. A third TNF inhibitor, etanercept, is approved for both PsA and the severe plaque of psoriasis.

In the study that served as the basis for the FDA approval of adalimumab for PsA, patients were stratified according to methotrexate use (yes or no) and degree of psoriatic involvement, and then randomized in a 1:1 ratio by site to receive either drug or placebo.

Of the 315 patients randomized to receive treatment, 162 were assigned to the placebo group and 153 were assigned to self-injected adalimumab 40 mg every other week. All patients who completed the 24-week protocol were eligible for long-term treatment in an open-label extension study.

The trial, which was conducted at 50 sites in the United States, Canada, and Europe, showed that patients treated with adalimumab achieved significantly higher American College of Rheumatology (ACR) response rates than those treated with placebo at all time points.

“At week 12, the ACR20 response rate was 58% for the adalimumab treatment group and 14% for the placebo-treated group,” study leader Philip J. Mease, M.D., of the Swedish Medical Center in Seattle, and his colleagues reported (Arthritis Rheum. 2005;52:3279–89).

“At week 24, the ACR 20 response rates were 57% and 15%, respectively. At 12 and 24 weeks, the ACR50 response rates were significantly higher in the adalimumab arm than in the placebo arm, and a significant difference in ACR 70 responses was also evident,” they said, adding that ACR responses developed rapidly, “with statistically significant between-group differences in the ACR20 and ACR50 responses observed at week 2”; 27% vs. 6% achieving ACR20 and 11% vs. 0% achieving ACR50. At week 4, 7% vs. 1% achieved ACR70.

Across the board, response rates did not differ between patients taking adalimumab in combination with methotrexate and those taking the TNF inhibitor alone.

The mean change in the modified total Sharp score in patients who had both baseline and week 24 radiographs was −0.2 for those on adalimumab compared with 1.0 for those receiving placebo injections (P less than .001), “implying that protection against progressive structural damage was achieved,” Dr. Mease said.

“Improvements seen in the skin manifestations of the disease were significant and occurred rapidly, results that were as good as or in some cases superior to results seen with other biologics,” Dr. Mease told this newspaper. “At week 24, PASI [psoriasis area and severity index] showed a 75% improvement in 16% of adalimumab-treated patients, compared with only 3% of placebo patients (P less than .001).

Similarly, the physician's global assessment of psoriasis resulted in ratings of the lesions as “clear” or “almost clear” in 67% of the 70 adalimumab-treated patients evaluated, compared with only 10% of the 70 placebo-treated patients evaluated for psoriasis (P less than .001).

“It appears that the response was a little faster in the skin with adalimumab, as has also been seen with infliximab, than with other biologics. When it comes to joint symptoms and important aspects such as quality of life, physical function, and inhibition of progressive joint damage, the three anti-TNF drugs are similar; but if you have a patient with really severe skin disease, there may be a slight advantage to using either infliximab or adalimumab,” Dr. Mease said.

The ink had hardly dried on this study when, in October, the FDA approved adalimumab for the treatment of PsA. “With etanercept, the PsA indication came ahead of the psoriasis indication, and the same is going to be true of adalimumab; that indication will likely follow once the pure psoriasis trials are fully considered by the FDA,” said Dr. Mease.

The cost of etanercept and adalimumab, when used for RA or PsA in the standard dose of 50 mg per week and 40 mg every other week, respectively, is similar, he said. “The comparative costs of these agents in psoriasis have yet to be fully understood, and ultimately will depend upon the dosages used to achieve optimal effects in the skin.”

Adalimumab was generally well tolerated during the 24-week trial. Common side effects “were similar to those seen in clinical trials involving patients with RA or were thought to be related to underlying disease,” according to the authors.

Serious adverse events were experienced by 12 patients, including 7 in the placebo group and 5 in the adalimumab group. In the latter, events included nasal septum disorder, toe arthrodesis, aggravation of convulsions, viral meningitis (attributed to West Nile virus) and renal calculus; most of these were considered unrelated to the study medication.

The authors stress that longer-term follow-up from the open-label extension study is needed to confirm these results. The study was supported by Abbott Laboratories.

Dr. Mease has received consulting fees or honoraria of less than $10,000/year from Abbott.

A third tumor necrosis factor inhibitor has been added to the arsenal of drugs approved for treating psoriatic arthritis.

Adalimumab, a fully human, anti-TNF monoclonal antibody, significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active psoriatic arthritis, according to the findings of multicenter study.

Adalimumab and infliximab have been approved by the Food and Drug Administration for the treatment of psoriatic arthritis (PsA), but not for the dermatologic treatment of psoriasis in the absence of joint involvement. A third TNF inhibitor, etanercept, is approved for both PsA and the severe plaque of psoriasis.

In the study that served as the basis for the FDA approval of adalimumab for PsA, patients were stratified according to methotrexate use (yes or no) and degree of psoriatic involvement, and then randomized in a 1:1 ratio by site to receive either drug or placebo.

Of the 315 patients randomized to receive treatment, 162 were assigned to the placebo group and 153 were assigned to self-injected adalimumab 40 mg every other week. All patients who completed the 24-week protocol were eligible for long-term treatment in an open-label extension study.

The trial, which was conducted at 50 sites in the United States, Canada, and Europe, showed that patients treated with adalimumab achieved significantly higher American College of Rheumatology (ACR) response rates than those treated with placebo at all time points.

“At week 12, the ACR20 response rate was 58% for the adalimumab treatment group and 14% for the placebo-treated group,” study leader Philip J. Mease, M.D., of the Swedish Medical Center in Seattle, and his colleagues reported (Arthritis Rheum. 2005;52:3279–89).

“At week 24, the ACR 20 response rates were 57% and 15%, respectively. At 12 and 24 weeks, the ACR50 response rates were significantly higher in the adalimumab arm than in the placebo arm, and a significant difference in ACR 70 responses was also evident,” they said, adding that ACR responses developed rapidly, “with statistically significant between-group differences in the ACR20 and ACR50 responses observed at week 2”; 27% vs. 6% achieving ACR20 and 11% vs. 0% achieving ACR50. At week 4, 7% vs. 1% achieved ACR70.

Across the board, response rates did not differ between patients taking adalimumab in combination with methotrexate and those taking the TNF inhibitor alone.

The mean change in the modified total Sharp score in patients who had both baseline and week 24 radiographs was −0.2 for those on adalimumab compared with 1.0 for those receiving placebo injections (P less than .001), “implying that protection against progressive structural damage was achieved,” Dr. Mease said.

“Improvements seen in the skin manifestations of the disease were significant and occurred rapidly, results that were as good as or in some cases superior to results seen with other biologics,” Dr. Mease told this newspaper. “At week 24, PASI [psoriasis area and severity index] showed a 75% improvement in 16% of adalimumab-treated patients, compared with only 3% of placebo patients (P less than .001).

Similarly, the physician's global assessment of psoriasis resulted in ratings of the lesions as “clear” or “almost clear” in 67% of the 70 adalimumab-treated patients evaluated, compared with only 10% of the 70 placebo-treated patients evaluated for psoriasis (P less than .001).

“It appears that the response was a little faster in the skin with adalimumab, as has also been seen with infliximab, than with other biologics. When it comes to joint symptoms and important aspects such as quality of life, physical function, and inhibition of progressive joint damage, the three anti-TNF drugs are similar; but if you have a patient with really severe skin disease, there may be a slight advantage to using either infliximab or adalimumab,” Dr. Mease said.

The ink had hardly dried on this study when, in October, the FDA approved adalimumab for the treatment of PsA. “With etanercept, the PsA indication came ahead of the psoriasis indication, and the same is going to be true of adalimumab; that indication will likely follow once the pure psoriasis trials are fully considered by the FDA,” said Dr. Mease.

The cost of etanercept and adalimumab, when used for RA or PsA in the standard dose of 50 mg per week and 40 mg every other week, respectively, is similar, he said. “The comparative costs of these agents in psoriasis have yet to be fully understood, and ultimately will depend upon the dosages used to achieve optimal effects in the skin.”

Adalimumab was generally well tolerated during the 24-week trial. Common side effects “were similar to those seen in clinical trials involving patients with RA or were thought to be related to underlying disease,” according to the authors.

Serious adverse events were experienced by 12 patients, including 7 in the placebo group and 5 in the adalimumab group. In the latter, events included nasal septum disorder, toe arthrodesis, aggravation of convulsions, viral meningitis (attributed to West Nile virus) and renal calculus; most of these were considered unrelated to the study medication.

The authors stress that longer-term follow-up from the open-label extension study is needed to confirm these results. The study was supported by Abbott Laboratories.

Dr. Mease has received consulting fees or honoraria of less than $10,000/year from Abbott.

A third tumor necrosis factor inhibitor has been added to the arsenal of drugs approved for treating psoriatic arthritis.

Adalimumab, a fully human, anti-TNF monoclonal antibody, significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active psoriatic arthritis, according to the findings of multicenter study.

Adalimumab and infliximab have been approved by the Food and Drug Administration for the treatment of psoriatic arthritis (PsA), but not for the dermatologic treatment of psoriasis in the absence of joint involvement. A third TNF inhibitor, etanercept, is approved for both PsA and the severe plaque of psoriasis.

In the study that served as the basis for the FDA approval of adalimumab for PsA, patients were stratified according to methotrexate use (yes or no) and degree of psoriatic involvement, and then randomized in a 1:1 ratio by site to receive either drug or placebo.

Of the 315 patients randomized to receive treatment, 162 were assigned to the placebo group and 153 were assigned to self-injected adalimumab 40 mg every other week. All patients who completed the 24-week protocol were eligible for long-term treatment in an open-label extension study.

The trial, which was conducted at 50 sites in the United States, Canada, and Europe, showed that patients treated with adalimumab achieved significantly higher American College of Rheumatology (ACR) response rates than those treated with placebo at all time points.

“At week 12, the ACR20 response rate was 58% for the adalimumab treatment group and 14% for the placebo-treated group,” study leader Philip J. Mease, M.D., of the Swedish Medical Center in Seattle, and his colleagues reported (Arthritis Rheum. 2005;52:3279–89).

“At week 24, the ACR 20 response rates were 57% and 15%, respectively. At 12 and 24 weeks, the ACR50 response rates were significantly higher in the adalimumab arm than in the placebo arm, and a significant difference in ACR 70 responses was also evident,” they said, adding that ACR responses developed rapidly, “with statistically significant between-group differences in the ACR20 and ACR50 responses observed at week 2”; 27% vs. 6% achieving ACR20 and 11% vs. 0% achieving ACR50. At week 4, 7% vs. 1% achieved ACR70.

Across the board, response rates did not differ between patients taking adalimumab in combination with methotrexate and those taking the TNF inhibitor alone.

The mean change in the modified total Sharp score in patients who had both baseline and week 24 radiographs was −0.2 for those on adalimumab compared with 1.0 for those receiving placebo injections (P less than .001), “implying that protection against progressive structural damage was achieved,” Dr. Mease said.

“Improvements seen in the skin manifestations of the disease were significant and occurred rapidly, results that were as good as or in some cases superior to results seen with other biologics,” Dr. Mease told this newspaper. “At week 24, PASI [psoriasis area and severity index] showed a 75% improvement in 16% of adalimumab-treated patients, compared with only 3% of placebo patients (P less than .001).

Similarly, the physician's global assessment of psoriasis resulted in ratings of the lesions as “clear” or “almost clear” in 67% of the 70 adalimumab-treated patients evaluated, compared with only 10% of the 70 placebo-treated patients evaluated for psoriasis (P less than .001).

“It appears that the response was a little faster in the skin with adalimumab, as has also been seen with infliximab, than with other biologics. When it comes to joint symptoms and important aspects such as quality of life, physical function, and inhibition of progressive joint damage, the three anti-TNF drugs are similar; but if you have a patient with really severe skin disease, there may be a slight advantage to using either infliximab or adalimumab,” Dr. Mease said.

The ink had hardly dried on this study when, in October, the FDA approved adalimumab for the treatment of PsA. “With etanercept, the PsA indication came ahead of the psoriasis indication, and the same is going to be true of adalimumab; that indication will likely follow once the pure psoriasis trials are fully considered by the FDA,” said Dr. Mease.

The cost of etanercept and adalimumab, when used for RA or PsA in the standard dose of 50 mg per week and 40 mg every other week, respectively, is similar, he said. “The comparative costs of these agents in psoriasis have yet to be fully understood, and ultimately will depend upon the dosages used to achieve optimal effects in the skin.”

Adalimumab was generally well tolerated during the 24-week trial. Common side effects “were similar to those seen in clinical trials involving patients with RA or were thought to be related to underlying disease,” according to the authors.

Serious adverse events were experienced by 12 patients, including 7 in the placebo group and 5 in the adalimumab group. In the latter, events included nasal septum disorder, toe arthrodesis, aggravation of convulsions, viral meningitis (attributed to West Nile virus) and renal calculus; most of these were considered unrelated to the study medication.

The authors stress that longer-term follow-up from the open-label extension study is needed to confirm these results. The study was supported by Abbott Laboratories.

Dr. Mease has received consulting fees or honoraria of less than $10,000/year from Abbott.

VIENNA — Ultrasound-guided intraarticular injection of hylan G-F 20 (Synvisc) in patients with hip osteoarthritis is safe, well tolerated, and results in reduced pain and improved function for up to 9 months post injection, Alberto Migliore, M.D., reported at the annual European Congress of Rheumatology.

Synvisc, a hyaluronan derivative, is injected in order to supplement synovial fluid that has lost its elastoviscosity due to osteoarthritis.

It is used routinely in patients with symptomatic knee osteoarthritis, a setting in which multiple studies have shown that the treatment provides pain relief with a low risk of adverse events.

Fewer data are available regarding Synvisc in hip osteoarthritis, in large part because hip injections are technically more difficult and require ultrasound guidance in order to achieve consistently good results, explained Dr. Migliore of San Pietro Hospital, Rome.

He reported on 223 patients with symptomatic hip osteoarthritis who received one or more intraarticular 2-mL Synvisc injections.

Sixty-two had bilateral hip osteoarthritis. Patients were followed for up to 9 months. They could receive a repeat injection every 3 months as needed. A total of 360 injections were administered.

Nineteen patients left the study in order to undergo hip replacement surgery.

Significant improvement occurred in all three study end points: osteoarthritis pain as self-assessed on a visual analog scale, need for nonsteroidal anti-inflammatory drugs, and clinical improvement as measured using the Lequesne index. (See chart.)

No local infections or systemic adverse events occurred.

The injection technique involved the use of a sterile biopsy guide attached to a 3.5-MHz convex or 7-MHz linear ultrasound transducer. The joint was imaged using an anterior parasagittal approach.

Now that the safety and efficacy of intraarticular Synvisc injections have been demonstrated in hip osteoarthritis, Dr. Migliore's next goals are to establish the optimal dosing regimen and determine whether the therapy exerts a disease-modifying effect.

VIENNA — Ultrasound-guided intraarticular injection of hylan G-F 20 (Synvisc) in patients with hip osteoarthritis is safe, well tolerated, and results in reduced pain and improved function for up to 9 months post injection, Alberto Migliore, M.D., reported at the annual European Congress of Rheumatology.

Synvisc, a hyaluronan derivative, is injected in order to supplement synovial fluid that has lost its elastoviscosity due to osteoarthritis.

It is used routinely in patients with symptomatic knee osteoarthritis, a setting in which multiple studies have shown that the treatment provides pain relief with a low risk of adverse events.

Fewer data are available regarding Synvisc in hip osteoarthritis, in large part because hip injections are technically more difficult and require ultrasound guidance in order to achieve consistently good results, explained Dr. Migliore of San Pietro Hospital, Rome.

He reported on 223 patients with symptomatic hip osteoarthritis who received one or more intraarticular 2-mL Synvisc injections.

Sixty-two had bilateral hip osteoarthritis. Patients were followed for up to 9 months. They could receive a repeat injection every 3 months as needed. A total of 360 injections were administered.

Nineteen patients left the study in order to undergo hip replacement surgery.

Significant improvement occurred in all three study end points: osteoarthritis pain as self-assessed on a visual analog scale, need for nonsteroidal anti-inflammatory drugs, and clinical improvement as measured using the Lequesne index. (See chart.)

No local infections or systemic adverse events occurred.

The injection technique involved the use of a sterile biopsy guide attached to a 3.5-MHz convex or 7-MHz linear ultrasound transducer. The joint was imaged using an anterior parasagittal approach.

Now that the safety and efficacy of intraarticular Synvisc injections have been demonstrated in hip osteoarthritis, Dr. Migliore's next goals are to establish the optimal dosing regimen and determine whether the therapy exerts a disease-modifying effect.

VIENNA — Ultrasound-guided intraarticular injection of hylan G-F 20 (Synvisc) in patients with hip osteoarthritis is safe, well tolerated, and results in reduced pain and improved function for up to 9 months post injection, Alberto Migliore, M.D., reported at the annual European Congress of Rheumatology.

Synvisc, a hyaluronan derivative, is injected in order to supplement synovial fluid that has lost its elastoviscosity due to osteoarthritis.

It is used routinely in patients with symptomatic knee osteoarthritis, a setting in which multiple studies have shown that the treatment provides pain relief with a low risk of adverse events.

Fewer data are available regarding Synvisc in hip osteoarthritis, in large part because hip injections are technically more difficult and require ultrasound guidance in order to achieve consistently good results, explained Dr. Migliore of San Pietro Hospital, Rome.

He reported on 223 patients with symptomatic hip osteoarthritis who received one or more intraarticular 2-mL Synvisc injections.

Sixty-two had bilateral hip osteoarthritis. Patients were followed for up to 9 months. They could receive a repeat injection every 3 months as needed. A total of 360 injections were administered.

Nineteen patients left the study in order to undergo hip replacement surgery.

Significant improvement occurred in all three study end points: osteoarthritis pain as self-assessed on a visual analog scale, need for nonsteroidal anti-inflammatory drugs, and clinical improvement as measured using the Lequesne index. (See chart.)

No local infections or systemic adverse events occurred.

The injection technique involved the use of a sterile biopsy guide attached to a 3.5-MHz convex or 7-MHz linear ultrasound transducer. The joint was imaged using an anterior parasagittal approach.

Now that the safety and efficacy of intraarticular Synvisc injections have been demonstrated in hip osteoarthritis, Dr. Migliore's next goals are to establish the optimal dosing regimen and determine whether the therapy exerts a disease-modifying effect.

CLEVELAND — Tumor necrosis factor-α blockade should not be instituted in patients with known multiple sclerosis and should be used with caution in patients with family histories or other risk factors for MS, according to Jeffrey A. Cohen, M.D., a neurologist at the Cleveland Clinic.

In addition, physicians should be alert to uncommon central nervous system manifestations in patients receiving tumor necrosis factor (TNF) blockade for their inflammatory diseases, he said at a meeting on the treatment of autoimmune and inflammatory disorders.

TNF inhibitors currently approved by the Food and Drug Administration include the monoclonal antibodies infliximab (Remicade) and adalimumab (Humira) and the fusion protein etanercept (Enbrel).

TNF blockade both prevents and abrogates demyelinating disease in vitro and in animal studies. However, in humans, TNF blockade actually increased MS activity, said Dr. Cohen, citing data from two studies of infliximab and the discontinued lenercept. “In addition, treatment of other diseases for which TNF inhibitors are highly effective, including rheumatoid arthritis, Crohn's disease, and psoriasis, on rare occasions leads to CNS inflammatory demyelinating syndromes,” said Dr. Cohen at a summit sponsored by the Cleveland Clinic.

Failure of a TNF antagonist therapy in MS may be due to pleiotropic aspects of TNF actions, he noted. “In the CNS, TNF mediates cellular apoptosis and tissue damage, has important immunoregulatory functions, and is involved in tissue repair and regeneration. This experience reminds us that in the development of novel therapeutics, one must be cautious in extrapolating from animal models to human disease and from the results in one human disease to another,” he said.

Discussion of restarting therapy in patients who have been taken off a TNF inhibition because they developed a CNS manifestation involved a hypothetical case representing a composite of patients created for teaching purposes: a 32-year-old woman with a 5-year history of active Crohn's disease unresponsive to 6-mercaptopurine, mesalamine (Pentasa), and budesonide. She was started on infliximab and responded after the third infusion with complete resolution of abdominal pain and cramping and with a marked reduction in the frequency of bowel movements.

“After 12 months of therapy, she developed gait imbalance and numbness and tingling of the hands and feet that worsened over several weeks, making it difficult for her to walk,” Dr. Cohen said. The patient's Crohn's disease remained quiescent. A cranial nerve exam was normal, and the woman had normal strength, mild spasticity in the legs, diffuse hyperreflexia with right Babinski's sign, mild ataxia of the arms and legs, decreased position sense in the hands and feet, and moderate gait ataxia.

The patient's erythrocyte sedimentation rate was 55, she did not have a lupus anticoagulant, her B₁₂ and copper were normal, and an antibody test was negative. An MRI of the cervical spine showed an ovoid lesion in the spinal cord at C3–4 with mild diffuse enhancement. A lumbar puncture showed mild mononuclear cell pleocytosis, normal glucose, mildly elevated protein, normal IgG index, and no oligoclonal bands Dr. Cohen said.

Infliximab therapy was discontinued, and the woman was treated with intravenous methylprednisolone for three days, with the dose tapered over 2 weeks. “Within 12 weeks, the neurologic symptoms had completely resolved,” said Dr. Cohen. “Repeat MRI showed resolution of enhancement of the spinal cord lesion and no other lesions in the brain or spinal cord. Her original Crohn's symptoms recurred, however, and did not respond to MTX [methotrexate] or budesonide. Her symptoms improved on prednisone 60 mg/day but returned when the dose was tapered. She said she had felt much better on infliximab and asked about the possibility of restarting it,” said Dr. Cohen. “The decision to restart infliximab must be based on weighing the risks from Crohn's disease and whether other treatment options exist versus the risk of a recurrent neurologic complication.”

“The differential diagnosis of neurologic manifestations in patients with immune mediated inflammatory disorders treated with TNF inhibitors is broad and includes neurologic complications of the underlying disease, neoplastic or infectious complications of TNF inhibitors, and direct neurologic complications of TNF inhibitors. Reported neurologic complications of TNF inhibitors include CNS demyelinating syndromes, aseptic meningitis, seizures, ischemic optic neuropathy, and demyelinating peripheral neuropathies,” according to Dr. Cohen.

“CNS demyelination can occur anytime after an anti-TNF agent is started, and clinical manifestations reflect the anatomic site of involvement. Demyelination has been reported with all TNF antagonists and thus appears to be a class effect.”

In terms of the nervous system, Dr. Cohen recommends avoiding TNF blockade for patients who are known to have MS or who might be at risk of MS; nor should TNF inhibitor infusions be given to patients who have had a previous clinically isolated CNS syndrome without the formal diagnosis of MS or to patients who have cranial MRIs that look suggestive of MS but do not yet have clinical manifestations, advised Dr. Cohen.

“If you're forced to use TNF blockade because your patient has inflammatory bowel disease, RA [rheumatoid arthritis], or psoriasis that is not responding well to other [treatments], you need to watch closely for potential CNS demyelination, and that should include both clinical monitoring and periodic MRI. If a patient develops a CNS complication, TNF blockade should be interrupted and the investigation should include neurologic assessment to clarify the nature of the complication. That evaluation should include lumbar puncture, and treatment should include a corticosteroid. If the patient continues to have CNS demyelinating events following discontinuation of TNF blockade, you've probably unmasked incipient MS, in which case I would consider disease-modifying therapy for MS,” Dr. Cohen said.

The neurologist advised against looking for MS in every patient prior to starting a TNF inhibitor for treatment of inflammatory bowel disease, rheumatoid arthritis, or psoriasis. “In particular, I would not obtain an MRI unless there was some clinical suggestion of potential [for MS].” However, uveitis is a different story: “Uveitis is a manifestation that can occur in MS, so I would look very carefully for any indication of MS involvement” before beginning TNF blockade.

CLEVELAND — Tumor necrosis factor-α blockade should not be instituted in patients with known multiple sclerosis and should be used with caution in patients with family histories or other risk factors for MS, according to Jeffrey A. Cohen, M.D., a neurologist at the Cleveland Clinic.

In addition, physicians should be alert to uncommon central nervous system manifestations in patients receiving tumor necrosis factor (TNF) blockade for their inflammatory diseases, he said at a meeting on the treatment of autoimmune and inflammatory disorders.

TNF inhibitors currently approved by the Food and Drug Administration include the monoclonal antibodies infliximab (Remicade) and adalimumab (Humira) and the fusion protein etanercept (Enbrel).

TNF blockade both prevents and abrogates demyelinating disease in vitro and in animal studies. However, in humans, TNF blockade actually increased MS activity, said Dr. Cohen, citing data from two studies of infliximab and the discontinued lenercept. “In addition, treatment of other diseases for which TNF inhibitors are highly effective, including rheumatoid arthritis, Crohn's disease, and psoriasis, on rare occasions leads to CNS inflammatory demyelinating syndromes,” said Dr. Cohen at a summit sponsored by the Cleveland Clinic.

Failure of a TNF antagonist therapy in MS may be due to pleiotropic aspects of TNF actions, he noted. “In the CNS, TNF mediates cellular apoptosis and tissue damage, has important immunoregulatory functions, and is involved in tissue repair and regeneration. This experience reminds us that in the development of novel therapeutics, one must be cautious in extrapolating from animal models to human disease and from the results in one human disease to another,” he said.

Discussion of restarting therapy in patients who have been taken off a TNF inhibition because they developed a CNS manifestation involved a hypothetical case representing a composite of patients created for teaching purposes: a 32-year-old woman with a 5-year history of active Crohn's disease unresponsive to 6-mercaptopurine, mesalamine (Pentasa), and budesonide. She was started on infliximab and responded after the third infusion with complete resolution of abdominal pain and cramping and with a marked reduction in the frequency of bowel movements.

“After 12 months of therapy, she developed gait imbalance and numbness and tingling of the hands and feet that worsened over several weeks, making it difficult for her to walk,” Dr. Cohen said. The patient's Crohn's disease remained quiescent. A cranial nerve exam was normal, and the woman had normal strength, mild spasticity in the legs, diffuse hyperreflexia with right Babinski's sign, mild ataxia of the arms and legs, decreased position sense in the hands and feet, and moderate gait ataxia.

The patient's erythrocyte sedimentation rate was 55, she did not have a lupus anticoagulant, her B₁₂ and copper were normal, and an antibody test was negative. An MRI of the cervical spine showed an ovoid lesion in the spinal cord at C3–4 with mild diffuse enhancement. A lumbar puncture showed mild mononuclear cell pleocytosis, normal glucose, mildly elevated protein, normal IgG index, and no oligoclonal bands Dr. Cohen said.

Infliximab therapy was discontinued, and the woman was treated with intravenous methylprednisolone for three days, with the dose tapered over 2 weeks. “Within 12 weeks, the neurologic symptoms had completely resolved,” said Dr. Cohen. “Repeat MRI showed resolution of enhancement of the spinal cord lesion and no other lesions in the brain or spinal cord. Her original Crohn's symptoms recurred, however, and did not respond to MTX [methotrexate] or budesonide. Her symptoms improved on prednisone 60 mg/day but returned when the dose was tapered. She said she had felt much better on infliximab and asked about the possibility of restarting it,” said Dr. Cohen. “The decision to restart infliximab must be based on weighing the risks from Crohn's disease and whether other treatment options exist versus the risk of a recurrent neurologic complication.”

“The differential diagnosis of neurologic manifestations in patients with immune mediated inflammatory disorders treated with TNF inhibitors is broad and includes neurologic complications of the underlying disease, neoplastic or infectious complications of TNF inhibitors, and direct neurologic complications of TNF inhibitors. Reported neurologic complications of TNF inhibitors include CNS demyelinating syndromes, aseptic meningitis, seizures, ischemic optic neuropathy, and demyelinating peripheral neuropathies,” according to Dr. Cohen.

“CNS demyelination can occur anytime after an anti-TNF agent is started, and clinical manifestations reflect the anatomic site of involvement. Demyelination has been reported with all TNF antagonists and thus appears to be a class effect.”

In terms of the nervous system, Dr. Cohen recommends avoiding TNF blockade for patients who are known to have MS or who might be at risk of MS; nor should TNF inhibitor infusions be given to patients who have had a previous clinically isolated CNS syndrome without the formal diagnosis of MS or to patients who have cranial MRIs that look suggestive of MS but do not yet have clinical manifestations, advised Dr. Cohen.

“If you're forced to use TNF blockade because your patient has inflammatory bowel disease, RA [rheumatoid arthritis], or psoriasis that is not responding well to other [treatments], you need to watch closely for potential CNS demyelination, and that should include both clinical monitoring and periodic MRI. If a patient develops a CNS complication, TNF blockade should be interrupted and the investigation should include neurologic assessment to clarify the nature of the complication. That evaluation should include lumbar puncture, and treatment should include a corticosteroid. If the patient continues to have CNS demyelinating events following discontinuation of TNF blockade, you've probably unmasked incipient MS, in which case I would consider disease-modifying therapy for MS,” Dr. Cohen said.

The neurologist advised against looking for MS in every patient prior to starting a TNF inhibitor for treatment of inflammatory bowel disease, rheumatoid arthritis, or psoriasis. “In particular, I would not obtain an MRI unless there was some clinical suggestion of potential [for MS].” However, uveitis is a different story: “Uveitis is a manifestation that can occur in MS, so I would look very carefully for any indication of MS involvement” before beginning TNF blockade.

CLEVELAND — Tumor necrosis factor-α blockade should not be instituted in patients with known multiple sclerosis and should be used with caution in patients with family histories or other risk factors for MS, according to Jeffrey A. Cohen, M.D., a neurologist at the Cleveland Clinic.

In addition, physicians should be alert to uncommon central nervous system manifestations in patients receiving tumor necrosis factor (TNF) blockade for their inflammatory diseases, he said at a meeting on the treatment of autoimmune and inflammatory disorders.

TNF inhibitors currently approved by the Food and Drug Administration include the monoclonal antibodies infliximab (Remicade) and adalimumab (Humira) and the fusion protein etanercept (Enbrel).

TNF blockade both prevents and abrogates demyelinating disease in vitro and in animal studies. However, in humans, TNF blockade actually increased MS activity, said Dr. Cohen, citing data from two studies of infliximab and the discontinued lenercept. “In addition, treatment of other diseases for which TNF inhibitors are highly effective, including rheumatoid arthritis, Crohn's disease, and psoriasis, on rare occasions leads to CNS inflammatory demyelinating syndromes,” said Dr. Cohen at a summit sponsored by the Cleveland Clinic.

Failure of a TNF antagonist therapy in MS may be due to pleiotropic aspects of TNF actions, he noted. “In the CNS, TNF mediates cellular apoptosis and tissue damage, has important immunoregulatory functions, and is involved in tissue repair and regeneration. This experience reminds us that in the development of novel therapeutics, one must be cautious in extrapolating from animal models to human disease and from the results in one human disease to another,” he said.

Discussion of restarting therapy in patients who have been taken off a TNF inhibition because they developed a CNS manifestation involved a hypothetical case representing a composite of patients created for teaching purposes: a 32-year-old woman with a 5-year history of active Crohn's disease unresponsive to 6-mercaptopurine, mesalamine (Pentasa), and budesonide. She was started on infliximab and responded after the third infusion with complete resolution of abdominal pain and cramping and with a marked reduction in the frequency of bowel movements.

“After 12 months of therapy, she developed gait imbalance and numbness and tingling of the hands and feet that worsened over several weeks, making it difficult for her to walk,” Dr. Cohen said. The patient's Crohn's disease remained quiescent. A cranial nerve exam was normal, and the woman had normal strength, mild spasticity in the legs, diffuse hyperreflexia with right Babinski's sign, mild ataxia of the arms and legs, decreased position sense in the hands and feet, and moderate gait ataxia.

The patient's erythrocyte sedimentation rate was 55, she did not have a lupus anticoagulant, her B₁₂ and copper were normal, and an antibody test was negative. An MRI of the cervical spine showed an ovoid lesion in the spinal cord at C3–4 with mild diffuse enhancement. A lumbar puncture showed mild mononuclear cell pleocytosis, normal glucose, mildly elevated protein, normal IgG index, and no oligoclonal bands Dr. Cohen said.

Infliximab therapy was discontinued, and the woman was treated with intravenous methylprednisolone for three days, with the dose tapered over 2 weeks. “Within 12 weeks, the neurologic symptoms had completely resolved,” said Dr. Cohen. “Repeat MRI showed resolution of enhancement of the spinal cord lesion and no other lesions in the brain or spinal cord. Her original Crohn's symptoms recurred, however, and did not respond to MTX [methotrexate] or budesonide. Her symptoms improved on prednisone 60 mg/day but returned when the dose was tapered. She said she had felt much better on infliximab and asked about the possibility of restarting it,” said Dr. Cohen. “The decision to restart infliximab must be based on weighing the risks from Crohn's disease and whether other treatment options exist versus the risk of a recurrent neurologic complication.”

“The differential diagnosis of neurologic manifestations in patients with immune mediated inflammatory disorders treated with TNF inhibitors is broad and includes neurologic complications of the underlying disease, neoplastic or infectious complications of TNF inhibitors, and direct neurologic complications of TNF inhibitors. Reported neurologic complications of TNF inhibitors include CNS demyelinating syndromes, aseptic meningitis, seizures, ischemic optic neuropathy, and demyelinating peripheral neuropathies,” according to Dr. Cohen.

“CNS demyelination can occur anytime after an anti-TNF agent is started, and clinical manifestations reflect the anatomic site of involvement. Demyelination has been reported with all TNF antagonists and thus appears to be a class effect.”

In terms of the nervous system, Dr. Cohen recommends avoiding TNF blockade for patients who are known to have MS or who might be at risk of MS; nor should TNF inhibitor infusions be given to patients who have had a previous clinically isolated CNS syndrome without the formal diagnosis of MS or to patients who have cranial MRIs that look suggestive of MS but do not yet have clinical manifestations, advised Dr. Cohen.

“If you're forced to use TNF blockade because your patient has inflammatory bowel disease, RA [rheumatoid arthritis], or psoriasis that is not responding well to other [treatments], you need to watch closely for potential CNS demyelination, and that should include both clinical monitoring and periodic MRI. If a patient develops a CNS complication, TNF blockade should be interrupted and the investigation should include neurologic assessment to clarify the nature of the complication. That evaluation should include lumbar puncture, and treatment should include a corticosteroid. If the patient continues to have CNS demyelinating events following discontinuation of TNF blockade, you've probably unmasked incipient MS, in which case I would consider disease-modifying therapy for MS,” Dr. Cohen said.

The neurologist advised against looking for MS in every patient prior to starting a TNF inhibitor for treatment of inflammatory bowel disease, rheumatoid arthritis, or psoriasis. “In particular, I would not obtain an MRI unless there was some clinical suggestion of potential [for MS].” However, uveitis is a different story: “Uveitis is a manifestation that can occur in MS, so I would look very carefully for any indication of MS involvement” before beginning TNF blockade.