Rheumatoid Arthritis

BOSTON — A strong and statistically significant correlation between systemic C-reactive protein levels and inflammatory infiltrates in the joints of individuals with osteoarthritis in a recent study offers clues into the mechanistic link between the systemic inflammatory marker and disease activity, Dr. Carla R. Scanzello said at the 10th World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Previous studies have demonstrated an association between systemic C-reactive protein (CRP) levels and disease progression, clinical severity, and pain in osteoarthritis.

But these findings are the first to link CRP levels to local inflammatory findings, Dr. Scanzello reported in a poster presentation.

To investigate the relationship between systemic CRP levels and local joint inflammation, Dr. Scanzello, with lead investigator Dr. Andrew Pearle and colleagues at the Hospital for Special Surgery in New York, evaluated the appearance, histology, and interleukin-6 (IL-6) levels in synovial fluid from 52 patients with ideopathic arthritis.

The investigators collected plasma and synovial membrane specimens from these patients, all of whom were scheduled to undergo total knee or hip arthroplasty or knee arthroscopy for osteoarthritis.

The researchers also collected joint fluid samples from a subgroup of 26 of these patients prior to surgery.

Synovial membrane inflammation was graded intraoperatively and by subsequent histologic examination, and synovial fluid IL-6 levels and plasma CRP levels were measured using a high-sensitivity enzyme-linked immunosorbent assay.

Of the full cohort, 26 patients had low-grade inflammatory infiltrates on histologic analysis and 4 patients had high-grade infiltrates.

The mean CRP level in the patients with inflammatory infiltrates was 4.7 μg/mL, which was significantly higher than the mean of 1.7 μg/mL in patients without inflammation. In addition, the degree of inflammation had a statistically significant correlation with systemic CRP levels (r = 0.42), Dr. Scanzello commented.

While there was no significant difference between patients with and without synovial infiltrates in mean age, body mass index, or gender, “there was a trend toward slightly higher BMI in the group with histologic infiltrates,” Dr. Scanzello said.

With respect to measures of IL-6, a known regulator of the acute phase response, “the plasma IL-6 levels were difficult to detect in most of the osteoarthritis patients.”

However, the average synovial fluid IL-6 level in the patients from whom synovial fluid samples were collected was 88.02 pg/mL, according to Dr. Scanzello.

There was a significant correlation between those levels and systemic CRP levels (r = 0.63), she said.

The investigators observed modest but statistically significant correlations between CRP levels and BMI, and multiple linear regression analysis revealed that both BMI and degree of inflammation were significantly associated with CRP levels.

While the significance of the BMI connection is unclear, “it's possible that patients with elevated BMI are more likely to develop inflammation within the joint,” said Dr. Scanzello.

The correlation between CRP and inflammatory infiltrates found in this investigation, taken together with results from earlier studies linking high CRP levels with more rapid disease progression and more severe pain, suggests that “osteoarthritis patients with elevated high-sensitivity CRP may make up a subgroup of patients with synovial inflammation and with a more aggressive form of disease,” Dr. Scanzello concluded.

BOSTON — A strong and statistically significant correlation between systemic C-reactive protein levels and inflammatory infiltrates in the joints of individuals with osteoarthritis in a recent study offers clues into the mechanistic link between the systemic inflammatory marker and disease activity, Dr. Carla R. Scanzello said at the 10th World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Previous studies have demonstrated an association between systemic C-reactive protein (CRP) levels and disease progression, clinical severity, and pain in osteoarthritis.

But these findings are the first to link CRP levels to local inflammatory findings, Dr. Scanzello reported in a poster presentation.

To investigate the relationship between systemic CRP levels and local joint inflammation, Dr. Scanzello, with lead investigator Dr. Andrew Pearle and colleagues at the Hospital for Special Surgery in New York, evaluated the appearance, histology, and interleukin-6 (IL-6) levels in synovial fluid from 52 patients with ideopathic arthritis.

The investigators collected plasma and synovial membrane specimens from these patients, all of whom were scheduled to undergo total knee or hip arthroplasty or knee arthroscopy for osteoarthritis.

The researchers also collected joint fluid samples from a subgroup of 26 of these patients prior to surgery.

Synovial membrane inflammation was graded intraoperatively and by subsequent histologic examination, and synovial fluid IL-6 levels and plasma CRP levels were measured using a high-sensitivity enzyme-linked immunosorbent assay.

Of the full cohort, 26 patients had low-grade inflammatory infiltrates on histologic analysis and 4 patients had high-grade infiltrates.

The mean CRP level in the patients with inflammatory infiltrates was 4.7 μg/mL, which was significantly higher than the mean of 1.7 μg/mL in patients without inflammation. In addition, the degree of inflammation had a statistically significant correlation with systemic CRP levels (r = 0.42), Dr. Scanzello commented.

While there was no significant difference between patients with and without synovial infiltrates in mean age, body mass index, or gender, “there was a trend toward slightly higher BMI in the group with histologic infiltrates,” Dr. Scanzello said.

With respect to measures of IL-6, a known regulator of the acute phase response, “the plasma IL-6 levels were difficult to detect in most of the osteoarthritis patients.”

However, the average synovial fluid IL-6 level in the patients from whom synovial fluid samples were collected was 88.02 pg/mL, according to Dr. Scanzello.

There was a significant correlation between those levels and systemic CRP levels (r = 0.63), she said.

The investigators observed modest but statistically significant correlations between CRP levels and BMI, and multiple linear regression analysis revealed that both BMI and degree of inflammation were significantly associated with CRP levels.

While the significance of the BMI connection is unclear, “it's possible that patients with elevated BMI are more likely to develop inflammation within the joint,” said Dr. Scanzello.

The correlation between CRP and inflammatory infiltrates found in this investigation, taken together with results from earlier studies linking high CRP levels with more rapid disease progression and more severe pain, suggests that “osteoarthritis patients with elevated high-sensitivity CRP may make up a subgroup of patients with synovial inflammation and with a more aggressive form of disease,” Dr. Scanzello concluded.

BOSTON — A strong and statistically significant correlation between systemic C-reactive protein levels and inflammatory infiltrates in the joints of individuals with osteoarthritis in a recent study offers clues into the mechanistic link between the systemic inflammatory marker and disease activity, Dr. Carla R. Scanzello said at the 10th World Congress on Osteoarthritis sponsored by the Osteoarthritis Research Society International.

Previous studies have demonstrated an association between systemic C-reactive protein (CRP) levels and disease progression, clinical severity, and pain in osteoarthritis.

But these findings are the first to link CRP levels to local inflammatory findings, Dr. Scanzello reported in a poster presentation.

To investigate the relationship between systemic CRP levels and local joint inflammation, Dr. Scanzello, with lead investigator Dr. Andrew Pearle and colleagues at the Hospital for Special Surgery in New York, evaluated the appearance, histology, and interleukin-6 (IL-6) levels in synovial fluid from 52 patients with ideopathic arthritis.

The investigators collected plasma and synovial membrane specimens from these patients, all of whom were scheduled to undergo total knee or hip arthroplasty or knee arthroscopy for osteoarthritis.

The researchers also collected joint fluid samples from a subgroup of 26 of these patients prior to surgery.

Synovial membrane inflammation was graded intraoperatively and by subsequent histologic examination, and synovial fluid IL-6 levels and plasma CRP levels were measured using a high-sensitivity enzyme-linked immunosorbent assay.

Of the full cohort, 26 patients had low-grade inflammatory infiltrates on histologic analysis and 4 patients had high-grade infiltrates.

The mean CRP level in the patients with inflammatory infiltrates was 4.7 μg/mL, which was significantly higher than the mean of 1.7 μg/mL in patients without inflammation. In addition, the degree of inflammation had a statistically significant correlation with systemic CRP levels (r = 0.42), Dr. Scanzello commented.

While there was no significant difference between patients with and without synovial infiltrates in mean age, body mass index, or gender, “there was a trend toward slightly higher BMI in the group with histologic infiltrates,” Dr. Scanzello said.

With respect to measures of IL-6, a known regulator of the acute phase response, “the plasma IL-6 levels were difficult to detect in most of the osteoarthritis patients.”

However, the average synovial fluid IL-6 level in the patients from whom synovial fluid samples were collected was 88.02 pg/mL, according to Dr. Scanzello.

There was a significant correlation between those levels and systemic CRP levels (r = 0.63), she said.

The investigators observed modest but statistically significant correlations between CRP levels and BMI, and multiple linear regression analysis revealed that both BMI and degree of inflammation were significantly associated with CRP levels.

While the significance of the BMI connection is unclear, “it's possible that patients with elevated BMI are more likely to develop inflammation within the joint,” said Dr. Scanzello.

The correlation between CRP and inflammatory infiltrates found in this investigation, taken together with results from earlier studies linking high CRP levels with more rapid disease progression and more severe pain, suggests that “osteoarthritis patients with elevated high-sensitivity CRP may make up a subgroup of patients with synovial inflammation and with a more aggressive form of disease,” Dr. Scanzello concluded.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

The Food and Drug Administration's MedWatch program has announced a voluntary recall of one lot of Methotrexate for Injection (preservative free) due to the presence of low levels of ethylene glycol.

Bedford Laboratories, a division of Ben Venue Laboratories Inc., last month announced a recall of Methotrexate for Injection (preservative free), USP 1 gram per vial (NDC 55390–143–01), Lot &num;859142, exp. 09/07. The company was informed by the manufacturer that the active drug substance used to create this lot contained low levels of ethylene glycol, a solvent used in antifreeze among other products.<[par]>

Methotrexate is an antimetabolite used in the treatment of adult rheumatoid arthritis, severe psoriasis, and certain neoplastic diseases.

Methotrexate for Injection was distributed to wholesalers and hospitals throughout the United States in October and November 2005.

Bedford Laboratories instructed customers to discontinue distribution and use of this lot, and to call the company at 800-562-4797 with any questions.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN DIEGO — Rheumatoid arthritis patients have a high rate of ischemic heart disease and high associated mortality, even compared with their siblings, Dr. Namita Kumar said at the annual meeting of the American College of Rheumatology.

The data from a review of death certificates clearly suggest that the increased coronary artery disease death risk seen among rheumatoid arthritis patients, compared with their unaffected siblings, is not due to genetics or upbringing but, rather, to the disease or its treatment, Dr. Kumar noted.

The investigators reviewed certificates from a cohort of rheumatoid arthritis patients and their same-sex, arthritis-free siblings who were involved in a study from 1980 to 1992. They found that during the study period the patients with rheumatoid arthritis were almost twice as likely as their siblings to die. The most common cause of death listed among participants with rheumatoid arthritis was coronary artery disease; in contrast, the most common cause of death for their siblings was malignancy. Fifty-four percent of the 257 rheumatoid arthritis patients died during the period, compared with 28% of the 371 same-sex siblings.

The age of death was not dissimilar (72 years versus 73 years). But the three major causes of death in the rheumatoid arthritis patients were coronary artery disease (35%), all-cause infection (34%), and malignancy (19%). The major causes of death in the siblings were malignancy (38%), all-cause infection (25%), and coronary artery disease (22%).

A similar percentage of patients and their siblings died from stroke (8% versus 10%), noted Dr. Kumar of Freeman Hospital, Newcastle upon Tyne, England.

Genetics, family history, and the environment do not account for the prevalence of ischemic heart disease in rheumatoid arthritis [patients], she said.

SAN ANTONIO — New prosthetic joint options for rheumatoid arthritis patients are a welcome alternative to conventional silicone implants for relieving pain and restoring function and stability, according to experts at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

New ball-and-joint prostheses relieve arthritic pain and restore articular and bony anatomy, providing more natural hand or forearm-wrist function and appearance and greater stability than provided by silicone implants, which break apart over time and may cause inflammation, said Dr. Richard A. Berger, a professor of orthopedics at the Mayo Clinic College of Medicine, Rochester, Minn., and consultant to Avanta Orthopaedics, San Diego.

Experience with silicone joint implants since their approval in the 1980s have shown that over time the implants tend to break apart, an outcome that can aggravate further inflammatory processes already underway in the joint, said Dr. Berger.

The newer implants promise both to remain structurally intact and to restore articular and bony anatomy, providing a more normal appearance to disfigured hands, said Dr. Robert D. Beckenbaugh, professor of orthopedics at the Mayo Clinic College of Medicine and consultant to Ascension Orthopedics Inc., Austin, Tex.

Dr. Berger noted that the Avanta uHead, replicating the distal ulnar head in the forearm, and the Scheker, a distal radioulnar joint (Aptis Medical, Louisville, Ky.), serve the same purpose but are used in patients with a different degree of problems. The uHead implant is a simple ball on a stem used to replace the end of the ulna when the patient has sufficient bone stock and soft tissue, he said. The Scheker ball-and-socket is used in patients with advanced degenerative rheumatoid disease because it connects directly to the ulnar rather than requiring bone stock or soft tissue to hold it in place.

The Avanta uHead joint is fabricated from a cobalt chrome-molybdenum alloy, and the stem is coated with titanium to promote osseointegration. Provided in right and left configurations and several sizes, the device stem is designed for snap-fit or can be cemented into the socket, which Dr. Berger noted improves the interface in rheumatoid disease patients with soft bone tissue, resulting in a more stable joint than without cement.

The Scheker prosthesis consists of a metal radial plate, socket, and ulna stem as well as an ultra-high-molecular-weight polyethylene ball for complete replacement of the joint, resulting in renewed range of motion that enables patients to use their hands for turning and lifting.

An initial clinical trial by Dr. Berger and Dr. William P. Cooney III, also a professor of orthopedics at Mayo Clinic College of Medicine, followed 26 patients with 28 ulnar head replacement arthroplasties for 30 months. Patients were an average of 51 years old, and all of them presented with pain, instability, or weakness or a combination of symptoms. Eighteen patients got “press-fit” implants, and 10 got cemented implants. At follow-up, 80% of patients were satisfied and reported no pain; 100% experienced improvement in symptoms, but 15% still had mild pain and one patient reported no pain relief. Postoperative pronation and supination of the forearm were 75 degrees and 70 degrees, respectively, and grip strength improved by 10%. There were two acute complications—an ulna shaft nondisplaced split fracture during impaction of the device and an acute dorsal sensory ulnar nerve neuropraxia—and four chronic complications: a neuroma, two cases of residual instability, and one case of implant loosening, all of which required revision surgery. The Mayo Clinic wrist score was used to assess outcomes, which were excellent in 4 patients, good in 18, and poor in 6.

Other options for treatment of hands disabled by arthritis or trauma are pyrocarbon implants for the proximal interphalangeal (PIP), trapeziometacarpal, and metacarpophalangeal (MCP) joints. Both the PIP pyrocarbon total joint and the MCP pyrocarbon total joint prostheses (Ascension Orthopedics) are made from a low-friction pyrolytic carbon-coated graphite substrate compound that has low wear properties and is biologically compatible with bone tissue, said Dr. Beckenbaugh.

The pyrocarbon PIP joint is a bicondylar, semiconstrained prosthesis for total joint replacement with anatomically shaped stems that press-fit into the intramedullary canal to achieve fixation by direct implant-to-bone apposition. The distal component has a bicupped design that allows slight sliding of the proximal condylar component and dorsal extensor to resist subluxation. Distal and proximal components come in four sizes, which can be matched with smaller or larger opposites to best fit the medullary canal of the patient's proximal and middle phalanx.

The pyrocarbon MCP joint replacement builds on pyrolytic carbon arthroplasty technology developed in 1977 but abandoned 10 years later for lack of funding. The new device uses the original MCP implant's simple ball-and-socket design, which had demonstrated very satisfactory results. A few modifications have been made; for example, the stems were enlarged and shaped to be a better physiologic fit with the medullary canal than the original design, the dorsal surface of the joint design was extended 10% to increase stability against volar subluxation, and the pyrolytic carbon material was strengthened through an improved manufacturing process.

Dr. Beckenbaugh pointed out that the success of ball-and-socket implants requires the capability to construct a stable soft tissue envelope to allow bony fixation by appositional bone growth. While these implants may be ideal for osteoarthritis, posttraumatic arthritis, and some rheumatoid patients, the old silicone or cemented implants may be preferred for rheumatoid patients with soft medullary tissue and thin cortical bone.

He said that the greatest potential problem with ball-and-socket design is subluxation and/or recurrent ulnar deviation, which can be prevented with careful surgical technique and postoperative care. The new devices require a longer postoperative immobilization (usually 3–4 weeks), compared with silicone arthroplasty, to allow soft tissue to heal and create stability before motion therapy is begun.

All of the protheses discussed by Dr. Berger and Dr. Beckenbaugh have received approval from the Food and Drug Administration for use in the United States and the CE Mark for approval in Europe.

Hand disabled by rheumatoid arthritis before use of PIP Pyrocarbon Implants.

Surgical placement of the PIP Pyrocarbon Implants enable hand flexion in same patient. Photos courtesy Dr. Robert D. Beckenbaugh

SAN ANTONIO — New prosthetic joint options for rheumatoid arthritis patients are a welcome alternative to conventional silicone implants for relieving pain and restoring function and stability, according to experts at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

New ball-and-joint prostheses relieve arthritic pain and restore articular and bony anatomy, providing more natural hand or forearm-wrist function and appearance and greater stability than provided by silicone implants, which break apart over time and may cause inflammation, said Dr. Richard A. Berger, a professor of orthopedics at the Mayo Clinic College of Medicine, Rochester, Minn., and consultant to Avanta Orthopaedics, San Diego.

Experience with silicone joint implants since their approval in the 1980s have shown that over time the implants tend to break apart, an outcome that can aggravate further inflammatory processes already underway in the joint, said Dr. Berger.

The newer implants promise both to remain structurally intact and to restore articular and bony anatomy, providing a more normal appearance to disfigured hands, said Dr. Robert D. Beckenbaugh, professor of orthopedics at the Mayo Clinic College of Medicine and consultant to Ascension Orthopedics Inc., Austin, Tex.

Dr. Berger noted that the Avanta uHead, replicating the distal ulnar head in the forearm, and the Scheker, a distal radioulnar joint (Aptis Medical, Louisville, Ky.), serve the same purpose but are used in patients with a different degree of problems. The uHead implant is a simple ball on a stem used to replace the end of the ulna when the patient has sufficient bone stock and soft tissue, he said. The Scheker ball-and-socket is used in patients with advanced degenerative rheumatoid disease because it connects directly to the ulnar rather than requiring bone stock or soft tissue to hold it in place.

The Avanta uHead joint is fabricated from a cobalt chrome-molybdenum alloy, and the stem is coated with titanium to promote osseointegration. Provided in right and left configurations and several sizes, the device stem is designed for snap-fit or can be cemented into the socket, which Dr. Berger noted improves the interface in rheumatoid disease patients with soft bone tissue, resulting in a more stable joint than without cement.

The Scheker prosthesis consists of a metal radial plate, socket, and ulna stem as well as an ultra-high-molecular-weight polyethylene ball for complete replacement of the joint, resulting in renewed range of motion that enables patients to use their hands for turning and lifting.

An initial clinical trial by Dr. Berger and Dr. William P. Cooney III, also a professor of orthopedics at Mayo Clinic College of Medicine, followed 26 patients with 28 ulnar head replacement arthroplasties for 30 months. Patients were an average of 51 years old, and all of them presented with pain, instability, or weakness or a combination of symptoms. Eighteen patients got “press-fit” implants, and 10 got cemented implants. At follow-up, 80% of patients were satisfied and reported no pain; 100% experienced improvement in symptoms, but 15% still had mild pain and one patient reported no pain relief. Postoperative pronation and supination of the forearm were 75 degrees and 70 degrees, respectively, and grip strength improved by 10%. There were two acute complications—an ulna shaft nondisplaced split fracture during impaction of the device and an acute dorsal sensory ulnar nerve neuropraxia—and four chronic complications: a neuroma, two cases of residual instability, and one case of implant loosening, all of which required revision surgery. The Mayo Clinic wrist score was used to assess outcomes, which were excellent in 4 patients, good in 18, and poor in 6.

Other options for treatment of hands disabled by arthritis or trauma are pyrocarbon implants for the proximal interphalangeal (PIP), trapeziometacarpal, and metacarpophalangeal (MCP) joints. Both the PIP pyrocarbon total joint and the MCP pyrocarbon total joint prostheses (Ascension Orthopedics) are made from a low-friction pyrolytic carbon-coated graphite substrate compound that has low wear properties and is biologically compatible with bone tissue, said Dr. Beckenbaugh.

The pyrocarbon PIP joint is a bicondylar, semiconstrained prosthesis for total joint replacement with anatomically shaped stems that press-fit into the intramedullary canal to achieve fixation by direct implant-to-bone apposition. The distal component has a bicupped design that allows slight sliding of the proximal condylar component and dorsal extensor to resist subluxation. Distal and proximal components come in four sizes, which can be matched with smaller or larger opposites to best fit the medullary canal of the patient's proximal and middle phalanx.

The pyrocarbon MCP joint replacement builds on pyrolytic carbon arthroplasty technology developed in 1977 but abandoned 10 years later for lack of funding. The new device uses the original MCP implant's simple ball-and-socket design, which had demonstrated very satisfactory results. A few modifications have been made; for example, the stems were enlarged and shaped to be a better physiologic fit with the medullary canal than the original design, the dorsal surface of the joint design was extended 10% to increase stability against volar subluxation, and the pyrolytic carbon material was strengthened through an improved manufacturing process.

Dr. Beckenbaugh pointed out that the success of ball-and-socket implants requires the capability to construct a stable soft tissue envelope to allow bony fixation by appositional bone growth. While these implants may be ideal for osteoarthritis, posttraumatic arthritis, and some rheumatoid patients, the old silicone or cemented implants may be preferred for rheumatoid patients with soft medullary tissue and thin cortical bone.

He said that the greatest potential problem with ball-and-socket design is subluxation and/or recurrent ulnar deviation, which can be prevented with careful surgical technique and postoperative care. The new devices require a longer postoperative immobilization (usually 3–4 weeks), compared with silicone arthroplasty, to allow soft tissue to heal and create stability before motion therapy is begun.

All of the protheses discussed by Dr. Berger and Dr. Beckenbaugh have received approval from the Food and Drug Administration for use in the United States and the CE Mark for approval in Europe.

Hand disabled by rheumatoid arthritis before use of PIP Pyrocarbon Implants.

Surgical placement of the PIP Pyrocarbon Implants enable hand flexion in same patient. Photos courtesy Dr. Robert D. Beckenbaugh

SAN ANTONIO — New prosthetic joint options for rheumatoid arthritis patients are a welcome alternative to conventional silicone implants for relieving pain and restoring function and stability, according to experts at the joint annual meeting of the American Society for Surgery of the Hand and the American Society of Hand Therapists.

New ball-and-joint prostheses relieve arthritic pain and restore articular and bony anatomy, providing more natural hand or forearm-wrist function and appearance and greater stability than provided by silicone implants, which break apart over time and may cause inflammation, said Dr. Richard A. Berger, a professor of orthopedics at the Mayo Clinic College of Medicine, Rochester, Minn., and consultant to Avanta Orthopaedics, San Diego.

Experience with silicone joint implants since their approval in the 1980s have shown that over time the implants tend to break apart, an outcome that can aggravate further inflammatory processes already underway in the joint, said Dr. Berger.

The newer implants promise both to remain structurally intact and to restore articular and bony anatomy, providing a more normal appearance to disfigured hands, said Dr. Robert D. Beckenbaugh, professor of orthopedics at the Mayo Clinic College of Medicine and consultant to Ascension Orthopedics Inc., Austin, Tex.

Dr. Berger noted that the Avanta uHead, replicating the distal ulnar head in the forearm, and the Scheker, a distal radioulnar joint (Aptis Medical, Louisville, Ky.), serve the same purpose but are used in patients with a different degree of problems. The uHead implant is a simple ball on a stem used to replace the end of the ulna when the patient has sufficient bone stock and soft tissue, he said. The Scheker ball-and-socket is used in patients with advanced degenerative rheumatoid disease because it connects directly to the ulnar rather than requiring bone stock or soft tissue to hold it in place.

The Avanta uHead joint is fabricated from a cobalt chrome-molybdenum alloy, and the stem is coated with titanium to promote osseointegration. Provided in right and left configurations and several sizes, the device stem is designed for snap-fit or can be cemented into the socket, which Dr. Berger noted improves the interface in rheumatoid disease patients with soft bone tissue, resulting in a more stable joint than without cement.

The Scheker prosthesis consists of a metal radial plate, socket, and ulna stem as well as an ultra-high-molecular-weight polyethylene ball for complete replacement of the joint, resulting in renewed range of motion that enables patients to use their hands for turning and lifting.

An initial clinical trial by Dr. Berger and Dr. William P. Cooney III, also a professor of orthopedics at Mayo Clinic College of Medicine, followed 26 patients with 28 ulnar head replacement arthroplasties for 30 months. Patients were an average of 51 years old, and all of them presented with pain, instability, or weakness or a combination of symptoms. Eighteen patients got “press-fit” implants, and 10 got cemented implants. At follow-up, 80% of patients were satisfied and reported no pain; 100% experienced improvement in symptoms, but 15% still had mild pain and one patient reported no pain relief. Postoperative pronation and supination of the forearm were 75 degrees and 70 degrees, respectively, and grip strength improved by 10%. There were two acute complications—an ulna shaft nondisplaced split fracture during impaction of the device and an acute dorsal sensory ulnar nerve neuropraxia—and four chronic complications: a neuroma, two cases of residual instability, and one case of implant loosening, all of which required revision surgery. The Mayo Clinic wrist score was used to assess outcomes, which were excellent in 4 patients, good in 18, and poor in 6.

Other options for treatment of hands disabled by arthritis or trauma are pyrocarbon implants for the proximal interphalangeal (PIP), trapeziometacarpal, and metacarpophalangeal (MCP) joints. Both the PIP pyrocarbon total joint and the MCP pyrocarbon total joint prostheses (Ascension Orthopedics) are made from a low-friction pyrolytic carbon-coated graphite substrate compound that has low wear properties and is biologically compatible with bone tissue, said Dr. Beckenbaugh.

The pyrocarbon PIP joint is a bicondylar, semiconstrained prosthesis for total joint replacement with anatomically shaped stems that press-fit into the intramedullary canal to achieve fixation by direct implant-to-bone apposition. The distal component has a bicupped design that allows slight sliding of the proximal condylar component and dorsal extensor to resist subluxation. Distal and proximal components come in four sizes, which can be matched with smaller or larger opposites to best fit the medullary canal of the patient's proximal and middle phalanx.

The pyrocarbon MCP joint replacement builds on pyrolytic carbon arthroplasty technology developed in 1977 but abandoned 10 years later for lack of funding. The new device uses the original MCP implant's simple ball-and-socket design, which had demonstrated very satisfactory results. A few modifications have been made; for example, the stems were enlarged and shaped to be a better physiologic fit with the medullary canal than the original design, the dorsal surface of the joint design was extended 10% to increase stability against volar subluxation, and the pyrolytic carbon material was strengthened through an improved manufacturing process.

Dr. Beckenbaugh pointed out that the success of ball-and-socket implants requires the capability to construct a stable soft tissue envelope to allow bony fixation by appositional bone growth. While these implants may be ideal for osteoarthritis, posttraumatic arthritis, and some rheumatoid patients, the old silicone or cemented implants may be preferred for rheumatoid patients with soft medullary tissue and thin cortical bone.

He said that the greatest potential problem with ball-and-socket design is subluxation and/or recurrent ulnar deviation, which can be prevented with careful surgical technique and postoperative care. The new devices require a longer postoperative immobilization (usually 3–4 weeks), compared with silicone arthroplasty, to allow soft tissue to heal and create stability before motion therapy is begun.

All of the protheses discussed by Dr. Berger and Dr. Beckenbaugh have received approval from the Food and Drug Administration for use in the United States and the CE Mark for approval in Europe.

Hand disabled by rheumatoid arthritis before use of PIP Pyrocarbon Implants.

Surgical placement of the PIP Pyrocarbon Implants enable hand flexion in same patient. Photos courtesy Dr. Robert D. Beckenbaugh

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.

SAN DIEGO — Adalimumab produces at least a 20% improvement in ankylosing spondylitis symptoms in half of patients who take the biologic for 24 weeks, according to an international placebo-controlled trial sponsored by the manufacturer.

“Adalimumab is clearly effective in ankylosing spondylitis,” Dr. Desiree van der Heijde said at the annual meeting of the American College of Rheumatology.

Although a direct comparison with infliximab was not made, the magnitude and likelihood of improvement seen with adalimumab in this trial are on par with what has been reported with infliximab in earlier studies, said Dr. van der Heijde, a professor of rheumatology at Maastricht University, the Netherlands.

The investigation included 208 patients treated with adalimumab (40 mg every other week) and 107 patients treated with placebo.

At 12 weeks, 58% of treated patients had a 20% improvement in their Assessments in Ankylosing Spondylitis score (ASAS 20) compared with 22% of placebo-treated patients; 38% had a 50% or better improvement (ASAS 50), compared with 11% of placebo-treated patients.

At 24 weeks, 50% of treated patients achieved a score of ASAS 20, compared with 20% of patients in the placebo group; 35% achieved a score of ASAS 50, compared with 12% of placebo-treated patients.

The study, which was funded by Abbott Laboratories, found no significant difference in adverse events, except for injection site reactions, which were noted in 11% of adalimumab-treated patients, compared with 3% of placebo-treated patients.

SAN DIEGO — Weight loss can profoundly improve function and pain in patients with knee osteoarthritis.

And even relatively minor weight loss of 15 lb in a moderately obese person can produce more improvement than an NSAID, Susan J. Bartlett, Ph.D., said at the annual meeting of the American College of Rheumatology.

“The more you lose, the greater the improvement,” said Dr. Bartlett, a rheumatologist at Johns Hopkins University, Baltimore.

Dr. Bartlett reported on a trial in which 48 patients who had knee osteoarthritis meeting American College of Rheumatology (ACR) criteria for significant impairment and were mildly or moderately obese (average body mass index 33 kg/m

The weight loss program consisted of 17 weekly classes on weight loss. Participants were encouraged to adopt a diet of 1,200–1,400 calories a day for women and 1,600–1,800 calories a day for men and to walk for exercise, gradually increasing to 30 minutes daily.

At intervention's end, patients had lost an average 15 lb and had a mean 49% decrease in their Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index total scores. WOMAC pain scores declined by a mean 39%, stiffness scores by 45%, and function scores by 49%.

Those improvements are greater than those reported for NSAID treatment in a recent trial comparing various COX-2 inhibitors with acetaminophen (J. Rheumatol. 2005;32:1093–105), Dr. Bartlett said.

The controls lost no weight and had no improvement in WOMAC.

The ACR's existing recommendations advise weight loss for osteoarthritis patients who are overweight. However, it has not been clear how much weight loss is needed to make a difference before this study, Dr. Bartlett said.

Findings from this study, though based on small numbers, suggest that the association between weight loss and WOMAC score approaches a dose/response, with even minimal loss producing improvement, Dr. Bartlett said.

She noted that research has suggested that there is a 9%–13% increased risk of a person developing knee osteoarthritis for every 2 lb of weight they gain.

SAN DIEGO — Weight loss can profoundly improve function and pain in patients with knee osteoarthritis.

And even relatively minor weight loss of 15 lb in a moderately obese person can produce more improvement than an NSAID, Susan J. Bartlett, Ph.D., said at the annual meeting of the American College of Rheumatology.

“The more you lose, the greater the improvement,” said Dr. Bartlett, a rheumatologist at Johns Hopkins University, Baltimore.

Dr. Bartlett reported on a trial in which 48 patients who had knee osteoarthritis meeting American College of Rheumatology (ACR) criteria for significant impairment and were mildly or moderately obese (average body mass index 33 kg/m

The weight loss program consisted of 17 weekly classes on weight loss. Participants were encouraged to adopt a diet of 1,200–1,400 calories a day for women and 1,600–1,800 calories a day for men and to walk for exercise, gradually increasing to 30 minutes daily.

At intervention's end, patients had lost an average 15 lb and had a mean 49% decrease in their Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index total scores. WOMAC pain scores declined by a mean 39%, stiffness scores by 45%, and function scores by 49%.

Those improvements are greater than those reported for NSAID treatment in a recent trial comparing various COX-2 inhibitors with acetaminophen (J. Rheumatol. 2005;32:1093–105), Dr. Bartlett said.

The controls lost no weight and had no improvement in WOMAC.

The ACR's existing recommendations advise weight loss for osteoarthritis patients who are overweight. However, it has not been clear how much weight loss is needed to make a difference before this study, Dr. Bartlett said.

Findings from this study, though based on small numbers, suggest that the association between weight loss and WOMAC score approaches a dose/response, with even minimal loss producing improvement, Dr. Bartlett said.

She noted that research has suggested that there is a 9%–13% increased risk of a person developing knee osteoarthritis for every 2 lb of weight they gain.

SAN DIEGO — Weight loss can profoundly improve function and pain in patients with knee osteoarthritis.

And even relatively minor weight loss of 15 lb in a moderately obese person can produce more improvement than an NSAID, Susan J. Bartlett, Ph.D., said at the annual meeting of the American College of Rheumatology.

“The more you lose, the greater the improvement,” said Dr. Bartlett, a rheumatologist at Johns Hopkins University, Baltimore.

Dr. Bartlett reported on a trial in which 48 patients who had knee osteoarthritis meeting American College of Rheumatology (ACR) criteria for significant impairment and were mildly or moderately obese (average body mass index 33 kg/m

The weight loss program consisted of 17 weekly classes on weight loss. Participants were encouraged to adopt a diet of 1,200–1,400 calories a day for women and 1,600–1,800 calories a day for men and to walk for exercise, gradually increasing to 30 minutes daily.

At intervention's end, patients had lost an average 15 lb and had a mean 49% decrease in their Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index total scores. WOMAC pain scores declined by a mean 39%, stiffness scores by 45%, and function scores by 49%.

Those improvements are greater than those reported for NSAID treatment in a recent trial comparing various COX-2 inhibitors with acetaminophen (J. Rheumatol. 2005;32:1093–105), Dr. Bartlett said.

The controls lost no weight and had no improvement in WOMAC.

The ACR's existing recommendations advise weight loss for osteoarthritis patients who are overweight. However, it has not been clear how much weight loss is needed to make a difference before this study, Dr. Bartlett said.

Findings from this study, though based on small numbers, suggest that the association between weight loss and WOMAC score approaches a dose/response, with even minimal loss producing improvement, Dr. Bartlett said.

She noted that research has suggested that there is a 9%–13% increased risk of a person developing knee osteoarthritis for every 2 lb of weight they gain.

Anti-tumor necrosis factor-α therapy may not always prevent the new onset or exacerbation of psoriatic skin lesions, according to a case series report involving patients taking the biologics for rheumatoid arthritis.

Infections, β-adrenergic blockers, or lithium were not present in any of the nine patients before the psoriasis erupted, reported Dr. Sonja Kary of Charité University Medicine Berlin, and associates (Arch. Rheum. Dis. [Epub ahead of print], Sept. 8, 2005). The diagnosis of rheumatoid arthritis was definite in all.

HLA typing revealed that one patient had HLA-Cw6, which is linked with psoriasis. Two patients had preexisting, but inactive, psoriasis. Nine patients were treated with adalimumab, etanercept, and infliximab at varying dosages for 4 days to 14 months prior to either new onset (five) or exacerbation (four). Some patients had previously received antimalarials that did not induce psoriasis.

Psoriasis vulgaris was diagnosed in six patients and pustulosis palmoplantaris in three, although pustular symptoms were present in five patients.

Withdrawing or reducing the dose of TNF-α-blocking agents led to improvement in some patients, but this approach was generally limited by the activity of the underlying rheumatoid arthritis. The severity of psoriatic symptoms was reduced when alternative anti-TNF-α agents were used.

Anti-tumor necrosis factor-α therapy may not always prevent the new onset or exacerbation of psoriatic skin lesions, according to a case series report involving patients taking the biologics for rheumatoid arthritis.

Infections, β-adrenergic blockers, or lithium were not present in any of the nine patients before the psoriasis erupted, reported Dr. Sonja Kary of Charité University Medicine Berlin, and associates (Arch. Rheum. Dis. [Epub ahead of print], Sept. 8, 2005). The diagnosis of rheumatoid arthritis was definite in all.

HLA typing revealed that one patient had HLA-Cw6, which is linked with psoriasis. Two patients had preexisting, but inactive, psoriasis. Nine patients were treated with adalimumab, etanercept, and infliximab at varying dosages for 4 days to 14 months prior to either new onset (five) or exacerbation (four). Some patients had previously received antimalarials that did not induce psoriasis.

Psoriasis vulgaris was diagnosed in six patients and pustulosis palmoplantaris in three, although pustular symptoms were present in five patients.

Withdrawing or reducing the dose of TNF-α-blocking agents led to improvement in some patients, but this approach was generally limited by the activity of the underlying rheumatoid arthritis. The severity of psoriatic symptoms was reduced when alternative anti-TNF-α agents were used.

Anti-tumor necrosis factor-α therapy may not always prevent the new onset or exacerbation of psoriatic skin lesions, according to a case series report involving patients taking the biologics for rheumatoid arthritis.

Infections, β-adrenergic blockers, or lithium were not present in any of the nine patients before the psoriasis erupted, reported Dr. Sonja Kary of Charité University Medicine Berlin, and associates (Arch. Rheum. Dis. [Epub ahead of print], Sept. 8, 2005). The diagnosis of rheumatoid arthritis was definite in all.

HLA typing revealed that one patient had HLA-Cw6, which is linked with psoriasis. Two patients had preexisting, but inactive, psoriasis. Nine patients were treated with adalimumab, etanercept, and infliximab at varying dosages for 4 days to 14 months prior to either new onset (five) or exacerbation (four). Some patients had previously received antimalarials that did not induce psoriasis.

Psoriasis vulgaris was diagnosed in six patients and pustulosis palmoplantaris in three, although pustular symptoms were present in five patients.

Withdrawing or reducing the dose of TNF-α-blocking agents led to improvement in some patients, but this approach was generally limited by the activity of the underlying rheumatoid arthritis. The severity of psoriatic symptoms was reduced when alternative anti-TNF-α agents were used.

LAS VEGAS — If a patient on a tumor necrosis factor inhibitor such as infliximab or etanercept presents with the signs and symptoms of infection, stop the drug immediately, Dr. Robert Orenstein advised at a dermatology seminar sponsored by the Skin Disease Education Foundation.

“You should do a very aggressive evaluation [because] many of these infections are disseminated at the time they present,” said Dr. Orenstein of the divisions of general internal medicine and infectious diseases at Mayo Medical School, Rochester, Minn. “You should start empiric therapy based upon what you think is going on, and you should withhold the agent until the etiology is completed. Don't use these agents if the patient has an active infection.”

He discussed his approach to patients on a TNF inhibitor who present with the following infections:

P Mycobacterial infections. Obtain a chest x-ray and a purified protein derivative (of tuberculin) skin test. As with AIDS patients, a 5-mm PPD skin test is considered positive.

“You also want to get an excellent history of exposure, particularly [from] people born in foreign countries or people who are at higher risk because of their profession, before you treat them,” Dr. Orenstein said. He noted that the QuantiFERON-TB Gold assay, a commercially available blood test, may be “very helpful” in distinguishing patients with nontuberculous infection from those who are positive for Mycobacterium tuberculosis. It takes 24 hours to get the results.

It remains unclear whether treatment of a latent tuberculosis infection needs to be completed before a patient begins taking a TNF inhibitor. “Most of us would argue that we would like to treat tuberculosis first, and after that use the [TNF] agent. But sometimes that's not a possibility. So in general we would recommend at least 1–2 months of treatment before initiating the biologic agent,” he said.

P Bacterial infections. The best way to prevent bacterial infections is to make sure these patients get Pneumovax and the influenza vaccines. Avoid live virus vaccines, he warned. Do not give the yellow fever vaccine to a patient on one of these agents.

P Viral infections. Make sure these patients are vaccinated for hepatitis A and B. If a patient on a TNF inhibitor presents with disseminated shingles or disseminated herpes simplex, stop the agent. Treat the patient with aggressive antiviral therapy, he added.

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

LAS VEGAS — If a patient on a tumor necrosis factor inhibitor such as infliximab or etanercept presents with the signs and symptoms of infection, stop the drug immediately, Dr. Robert Orenstein advised at a dermatology seminar sponsored by the Skin Disease Education Foundation.

“You should do a very aggressive evaluation [because] many of these infections are disseminated at the time they present,” said Dr. Orenstein of the divisions of general internal medicine and infectious diseases at Mayo Medical School, Rochester, Minn. “You should start empiric therapy based upon what you think is going on, and you should withhold the agent until the etiology is completed. Don't use these agents if the patient has an active infection.”

He discussed his approach to patients on a TNF inhibitor who present with the following infections:

P Mycobacterial infections. Obtain a chest x-ray and a purified protein derivative (of tuberculin) skin test. As with AIDS patients, a 5-mm PPD skin test is considered positive.

“You also want to get an excellent history of exposure, particularly [from] people born in foreign countries or people who are at higher risk because of their profession, before you treat them,” Dr. Orenstein said. He noted that the QuantiFERON-TB Gold assay, a commercially available blood test, may be “very helpful” in distinguishing patients with nontuberculous infection from those who are positive for Mycobacterium tuberculosis. It takes 24 hours to get the results.

It remains unclear whether treatment of a latent tuberculosis infection needs to be completed before a patient begins taking a TNF inhibitor. “Most of us would argue that we would like to treat tuberculosis first, and after that use the [TNF] agent. But sometimes that's not a possibility. So in general we would recommend at least 1–2 months of treatment before initiating the biologic agent,” he said.

P Bacterial infections. The best way to prevent bacterial infections is to make sure these patients get Pneumovax and the influenza vaccines. Avoid live virus vaccines, he warned. Do not give the yellow fever vaccine to a patient on one of these agents.

P Viral infections. Make sure these patients are vaccinated for hepatitis A and B. If a patient on a TNF inhibitor presents with disseminated shingles or disseminated herpes simplex, stop the agent. Treat the patient with aggressive antiviral therapy, he added.

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

LAS VEGAS — If a patient on a tumor necrosis factor inhibitor such as infliximab or etanercept presents with the signs and symptoms of infection, stop the drug immediately, Dr. Robert Orenstein advised at a dermatology seminar sponsored by the Skin Disease Education Foundation.

“You should do a very aggressive evaluation [because] many of these infections are disseminated at the time they present,” said Dr. Orenstein of the divisions of general internal medicine and infectious diseases at Mayo Medical School, Rochester, Minn. “You should start empiric therapy based upon what you think is going on, and you should withhold the agent until the etiology is completed. Don't use these agents if the patient has an active infection.”

He discussed his approach to patients on a TNF inhibitor who present with the following infections:

P Mycobacterial infections. Obtain a chest x-ray and a purified protein derivative (of tuberculin) skin test. As with AIDS patients, a 5-mm PPD skin test is considered positive.

“You also want to get an excellent history of exposure, particularly [from] people born in foreign countries or people who are at higher risk because of their profession, before you treat them,” Dr. Orenstein said. He noted that the QuantiFERON-TB Gold assay, a commercially available blood test, may be “very helpful” in distinguishing patients with nontuberculous infection from those who are positive for Mycobacterium tuberculosis. It takes 24 hours to get the results.

It remains unclear whether treatment of a latent tuberculosis infection needs to be completed before a patient begins taking a TNF inhibitor. “Most of us would argue that we would like to treat tuberculosis first, and after that use the [TNF] agent. But sometimes that's not a possibility. So in general we would recommend at least 1–2 months of treatment before initiating the biologic agent,” he said.

P Bacterial infections. The best way to prevent bacterial infections is to make sure these patients get Pneumovax and the influenza vaccines. Avoid live virus vaccines, he warned. Do not give the yellow fever vaccine to a patient on one of these agents.

P Viral infections. Make sure these patients are vaccinated for hepatitis A and B. If a patient on a TNF inhibitor presents with disseminated shingles or disseminated herpes simplex, stop the agent. Treat the patient with aggressive antiviral therapy, he added.

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

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant. Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups—28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group—even though there was a slightly higher percentage with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked. The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant. Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups—28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group—even though there was a slightly higher percentage with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked. The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

SAN DIEGO — Vitamin D supplementation did not lessen fibromyalgia symptoms in a small trial, a finding that casts doubt on the theory that vitamin D deficiency underlies some patients' pain and that screening vitamin D levels would identify patients who would benefit from supplementation, Dr. Ann Warner said in a poster presentation at the annual meeting of the American College of Rheumatology.

She performed two studies examining the vitamin D hypothesis. In one study, Dr. Warner, a rheumatologist who practices in Kansas City, Mo., took 50 fibromyalgia patients with insufficient serum levels of vitamin D (a 25-hydroxyvitamin D level less than 20 ng/mL) and randomized them to weekly doses of 50,000 IU of vitamin D or to placebo for 3 months.

The 25 patients who were randomized to supplementation had a higher mean pain score on a visual analog scale at baseline compared with the patients who received placebo (74 mm vs. 61 mm). The mean pain score of patients given supplemental vitamin D improved after 3 months, falling to 64 mm. However, the mean visual analog scale score of the control patients fell to a similar degree, to 54 mm, and neither group's changes were statistically significant. Patients in the control group showed a slight, but significant improvement on the functional pain score, while the supplemented group did not.

In the second study, Dr. Warner compared 25-hydroxyvitamin D levels in 104 patients with osteoarthritis with levels in 184 fibromyalgia patients.

There was no statistically significant difference in mean levels between the groups—28.76 ng/mL for the osteoarthritis group versus 29.16 for the fibromyalgia group—even though there was a slightly higher percentage with fibromyalgia who were insufficient, 29% versus 20%.

In an interview, Dr. Warner said the vitamin D hypothesis achieved some credibility in 2003 when an article in the Mayo Clinic Proceedings reported that 93% of a group of 150 patients with diffuse musculoskeletal pain were vitamin D insufficient. The article was accompanied by an editorial suggesting that vitamin D insufficiency is so common that all patients with diffuse pain should perhaps have their levels checked. The theory seemed to make sense, since vitamin D deficiency causes osteomalacia.

Her studies had some possibly confounding features, Dr. Warner said. In the supplementation study, even the control patients had an improvement in their vitamin D levels during the course of the study because the weather turned warmer. And in the second study, the osteoarthritis patients were significantly older (an average of 60 years versus 54 years).

Still, neither group in the first study had a significant change in their visual analog scale pain scores, and age did not correlate statistically with vitamin D level in the second study.

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week.

His analysis included 100 patients randomly selected from each of the four groups. These patients were selected from the entire 1,200-patient cohort, which included 300 participants in each of the four study arms. The structure and density of trabecular bone in the medial tibial compartment were examined using an x-ray technique developed by Dr. Buckland-Wright.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone.

Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, according to Dr. Buckland-Wright.

The patients with progressive narrowing on placebo and on the 5-mg a day dose continued to have bone loss, and had a greater degree of bone loss than those without progressive narrowing during the trial, who had no evidence of benefit at any dose.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week.

His analysis included 100 patients randomly selected from each of the four groups. These patients were selected from the entire 1,200-patient cohort, which included 300 participants in each of the four study arms. The structure and density of trabecular bone in the medial tibial compartment were examined using an x-ray technique developed by Dr. Buckland-Wright.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone.

Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, according to Dr. Buckland-Wright.

The patients with progressive narrowing on placebo and on the 5-mg a day dose continued to have bone loss, and had a greater degree of bone loss than those without progressive narrowing during the trial, who had no evidence of benefit at any dose.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week.

His analysis included 100 patients randomly selected from each of the four groups. These patients were selected from the entire 1,200-patient cohort, which included 300 participants in each of the four study arms. The structure and density of trabecular bone in the medial tibial compartment were examined using an x-ray technique developed by Dr. Buckland-Wright.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone.

Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, according to Dr. Buckland-Wright.

The patients with progressive narrowing on placebo and on the 5-mg a day dose continued to have bone loss, and had a greater degree of bone loss than those without progressive narrowing during the trial, who had no evidence of benefit at any dose.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.