Rheumatoid Arthritis

A small number of patients using infliximab (Remicade) have had very severe hepatic reactions, according to a revision of the package prescribing information.

In announcing the new safety information, the Food and Drug Administration and Centocor Inc. said there have been 35 cases of severe hepatic reactions in patients using infliximab reported in postmarketing data and 3 cases reported in clinical trials.

The reactions have included acute liver failure, jaundice, hepatitis, and cholestasis. Some cases were fatal or resulted in liver transplantation. They occurred from 2 weeks after starting therapy to more than a year after initiation. A causal relationship with infliximab has not been established, but treatment with the biologic can induce autoantibodies and autoimmune hepatitis has been diagnosed in some of the cases.

According to the warning, patients with signs of liver dysfunction should be evaluated. If jaundice or elevations in liver enzymes (greater than 5 times the upper limit of normal) occur, the biologic should be stopped and an investigation undertaken.

In clinical trials, mild to moderate elevations in liver enzymes were noted, without progression to severe hepatic injury.

In addition to the hepatic-reaction warning, Centocor added a warning that patients receiving infliximab may be at an increased risk of developing pneumonia, based on data from clinical trials data in rheumatoid arthritis patients.

Infliximab is approved for rheumatoid arthritis and Crohn's disease; in December, it was approved for ankylosing spondylitis.

A small number of patients using infliximab (Remicade) have had very severe hepatic reactions, according to a revision of the package prescribing information.

In announcing the new safety information, the Food and Drug Administration and Centocor Inc. said there have been 35 cases of severe hepatic reactions in patients using infliximab reported in postmarketing data and 3 cases reported in clinical trials.

The reactions have included acute liver failure, jaundice, hepatitis, and cholestasis. Some cases were fatal or resulted in liver transplantation. They occurred from 2 weeks after starting therapy to more than a year after initiation. A causal relationship with infliximab has not been established, but treatment with the biologic can induce autoantibodies and autoimmune hepatitis has been diagnosed in some of the cases.

According to the warning, patients with signs of liver dysfunction should be evaluated. If jaundice or elevations in liver enzymes (greater than 5 times the upper limit of normal) occur, the biologic should be stopped and an investigation undertaken.

In clinical trials, mild to moderate elevations in liver enzymes were noted, without progression to severe hepatic injury.

In addition to the hepatic-reaction warning, Centocor added a warning that patients receiving infliximab may be at an increased risk of developing pneumonia, based on data from clinical trials data in rheumatoid arthritis patients.

Infliximab is approved for rheumatoid arthritis and Crohn's disease; in December, it was approved for ankylosing spondylitis.

A small number of patients using infliximab (Remicade) have had very severe hepatic reactions, according to a revision of the package prescribing information.

In announcing the new safety information, the Food and Drug Administration and Centocor Inc. said there have been 35 cases of severe hepatic reactions in patients using infliximab reported in postmarketing data and 3 cases reported in clinical trials.

The reactions have included acute liver failure, jaundice, hepatitis, and cholestasis. Some cases were fatal or resulted in liver transplantation. They occurred from 2 weeks after starting therapy to more than a year after initiation. A causal relationship with infliximab has not been established, but treatment with the biologic can induce autoantibodies and autoimmune hepatitis has been diagnosed in some of the cases.

According to the warning, patients with signs of liver dysfunction should be evaluated. If jaundice or elevations in liver enzymes (greater than 5 times the upper limit of normal) occur, the biologic should be stopped and an investigation undertaken.

In clinical trials, mild to moderate elevations in liver enzymes were noted, without progression to severe hepatic injury.

In addition to the hepatic-reaction warning, Centocor added a warning that patients receiving infliximab may be at an increased risk of developing pneumonia, based on data from clinical trials data in rheumatoid arthritis patients.

Infliximab is approved for rheumatoid arthritis and Crohn's disease; in December, it was approved for ankylosing spondylitis.

SAN ANTONIO — Rheumatoid arthritis patients who are on tumor necrosis factor-inhibitor therapy have a fourfold greater risk of developing deep postoperative infections, according to a Johns Hopkins University review of patients who had undergone orthopedic procedures.

The findings, although not definitive, suggest that these agents should be stopped before surgery, Jon T. Giles, M.D., said at the annual meeting of the American College of Rheumatology.

Based on each agent's half-life, Dr. Giles recommended that etanercept be discontinued 2 weeks before surgery, infliximab 8 weeks before surgery, and adalimumab 4 weeks before surgery.

“In addition, we recommend avoidance of TNF inhibitors for 2 weeks after surgery,” he said.

Even without adding the biologics, patients with rheumatoid arthritis already have a higher risk of postoperative infection, noted Dr. Giles of Johns Hopkins University, Baltimore. Compared with a 1% rate of infection among people in the general population undergoing orthopedic procedures, infection rates among rheumatoid arthritis patients are two- to fourfold higher.

Dr. Giles's investigation involved 91 RA patients who had undergone a bone or joint surgical procedure in a Johns Hopkins clinic during a 5-year period from the beginning of 1999. Half of those patients had large joint arthroplasty procedures, and the rest were divided between fusion or resection procedures with no implanted materials and small joint procedures.

Among the 35 patients identified to be on biologic therapy at the time of surgery, seven developed early, deep, postoperative infections, including two cases of osteomyelitis, three cases of septic arthritis, and two cases of paraspinal abscess. There were three infections among the 56 patients not taking a biologic.

Patients on TNF-inhibitor therapy had an unadjusted 4.4 odds ratio for developing infection, compared with those patients not on the biologics; after adjustments for age, gender, and disease duration, the odds ratio rose to 4.6. After adjustment for prednisone use, diabetes, and presence of rheumatoid factor, the odds ratio was 5.3.

Given the study's small numbers, it could not be determined if the risk of infection varied by the type of surgery, site of surgery, or particular biologic agent used.

SAN ANTONIO — Rheumatoid arthritis patients who are on tumor necrosis factor-inhibitor therapy have a fourfold greater risk of developing deep postoperative infections, according to a Johns Hopkins University review of patients who had undergone orthopedic procedures.

The findings, although not definitive, suggest that these agents should be stopped before surgery, Jon T. Giles, M.D., said at the annual meeting of the American College of Rheumatology.

Based on each agent's half-life, Dr. Giles recommended that etanercept be discontinued 2 weeks before surgery, infliximab 8 weeks before surgery, and adalimumab 4 weeks before surgery.

“In addition, we recommend avoidance of TNF inhibitors for 2 weeks after surgery,” he said.

Even without adding the biologics, patients with rheumatoid arthritis already have a higher risk of postoperative infection, noted Dr. Giles of Johns Hopkins University, Baltimore. Compared with a 1% rate of infection among people in the general population undergoing orthopedic procedures, infection rates among rheumatoid arthritis patients are two- to fourfold higher.

Dr. Giles's investigation involved 91 RA patients who had undergone a bone or joint surgical procedure in a Johns Hopkins clinic during a 5-year period from the beginning of 1999. Half of those patients had large joint arthroplasty procedures, and the rest were divided between fusion or resection procedures with no implanted materials and small joint procedures.

Among the 35 patients identified to be on biologic therapy at the time of surgery, seven developed early, deep, postoperative infections, including two cases of osteomyelitis, three cases of septic arthritis, and two cases of paraspinal abscess. There were three infections among the 56 patients not taking a biologic.

Patients on TNF-inhibitor therapy had an unadjusted 4.4 odds ratio for developing infection, compared with those patients not on the biologics; after adjustments for age, gender, and disease duration, the odds ratio rose to 4.6. After adjustment for prednisone use, diabetes, and presence of rheumatoid factor, the odds ratio was 5.3.

Given the study's small numbers, it could not be determined if the risk of infection varied by the type of surgery, site of surgery, or particular biologic agent used.

SAN ANTONIO — Rheumatoid arthritis patients who are on tumor necrosis factor-inhibitor therapy have a fourfold greater risk of developing deep postoperative infections, according to a Johns Hopkins University review of patients who had undergone orthopedic procedures.

The findings, although not definitive, suggest that these agents should be stopped before surgery, Jon T. Giles, M.D., said at the annual meeting of the American College of Rheumatology.

Based on each agent's half-life, Dr. Giles recommended that etanercept be discontinued 2 weeks before surgery, infliximab 8 weeks before surgery, and adalimumab 4 weeks before surgery.

“In addition, we recommend avoidance of TNF inhibitors for 2 weeks after surgery,” he said.

Even without adding the biologics, patients with rheumatoid arthritis already have a higher risk of postoperative infection, noted Dr. Giles of Johns Hopkins University, Baltimore. Compared with a 1% rate of infection among people in the general population undergoing orthopedic procedures, infection rates among rheumatoid arthritis patients are two- to fourfold higher.

Dr. Giles's investigation involved 91 RA patients who had undergone a bone or joint surgical procedure in a Johns Hopkins clinic during a 5-year period from the beginning of 1999. Half of those patients had large joint arthroplasty procedures, and the rest were divided between fusion or resection procedures with no implanted materials and small joint procedures.

Among the 35 patients identified to be on biologic therapy at the time of surgery, seven developed early, deep, postoperative infections, including two cases of osteomyelitis, three cases of septic arthritis, and two cases of paraspinal abscess. There were three infections among the 56 patients not taking a biologic.

Patients on TNF-inhibitor therapy had an unadjusted 4.4 odds ratio for developing infection, compared with those patients not on the biologics; after adjustments for age, gender, and disease duration, the odds ratio rose to 4.6. After adjustment for prednisone use, diabetes, and presence of rheumatoid factor, the odds ratio was 5.3.

Given the study's small numbers, it could not be determined if the risk of infection varied by the type of surgery, site of surgery, or particular biologic agent used.

The U.S. Food and Drug Administration has accepted Centocor Inc.'s application to approve infliximab (Remicade) for the treatment of psoriatic arthritis.

Already approved for use in rheumatoid arthritis and Crohn's disease in North America, the European Union, and Japan, infliximab was recently approved for use in psoriatic arthritis by the European Commission.

Centocor, a wholly owned subsidiary of Johnson & Johnson, based its application on two double-blind, placebo-controlled studies involving a total of 304 patients with psoriatic arthritis. In one study, 65% of the patients on infliximab (5 mg/kg) achieved at least a 20% improvement, according to American College of Rheumatology (ACR20) criteria at week 16.

In the second study, some patients taking 5 mg/kg of infliximab began showing improvement as early as week 2. By week 14, 58% of the patients taking infliximab and only 11% of the patients taking placebo achieved ACR20 improvement. The Psoriasis Area and Severity Index score improved by 75% in 63.9% of the infliximab patients and only 2.3% of the placebo patients. Both differences were statistically significant.

Patients with psoriatic arthritis tolerated infliximab well in these studies, with an elevation in liver function tests being the most common abnormality associated with the drug, which inhibits tumor necrosis factor alpha. Investigators noted no deaths, cases of tuberculosis, or other opportunistic infections among the patients taking infliximab in these studies.

The U.S. Food and Drug Administration has accepted Centocor Inc.'s application to approve infliximab (Remicade) for the treatment of psoriatic arthritis.

Already approved for use in rheumatoid arthritis and Crohn's disease in North America, the European Union, and Japan, infliximab was recently approved for use in psoriatic arthritis by the European Commission.

Centocor, a wholly owned subsidiary of Johnson & Johnson, based its application on two double-blind, placebo-controlled studies involving a total of 304 patients with psoriatic arthritis. In one study, 65% of the patients on infliximab (5 mg/kg) achieved at least a 20% improvement, according to American College of Rheumatology (ACR20) criteria at week 16.

In the second study, some patients taking 5 mg/kg of infliximab began showing improvement as early as week 2. By week 14, 58% of the patients taking infliximab and only 11% of the patients taking placebo achieved ACR20 improvement. The Psoriasis Area and Severity Index score improved by 75% in 63.9% of the infliximab patients and only 2.3% of the placebo patients. Both differences were statistically significant.

Patients with psoriatic arthritis tolerated infliximab well in these studies, with an elevation in liver function tests being the most common abnormality associated with the drug, which inhibits tumor necrosis factor alpha. Investigators noted no deaths, cases of tuberculosis, or other opportunistic infections among the patients taking infliximab in these studies.

The U.S. Food and Drug Administration has accepted Centocor Inc.'s application to approve infliximab (Remicade) for the treatment of psoriatic arthritis.

Already approved for use in rheumatoid arthritis and Crohn's disease in North America, the European Union, and Japan, infliximab was recently approved for use in psoriatic arthritis by the European Commission.

Centocor, a wholly owned subsidiary of Johnson & Johnson, based its application on two double-blind, placebo-controlled studies involving a total of 304 patients with psoriatic arthritis. In one study, 65% of the patients on infliximab (5 mg/kg) achieved at least a 20% improvement, according to American College of Rheumatology (ACR20) criteria at week 16.

In the second study, some patients taking 5 mg/kg of infliximab began showing improvement as early as week 2. By week 14, 58% of the patients taking infliximab and only 11% of the patients taking placebo achieved ACR20 improvement. The Psoriasis Area and Severity Index score improved by 75% in 63.9% of the infliximab patients and only 2.3% of the placebo patients. Both differences were statistically significant.

Patients with psoriatic arthritis tolerated infliximab well in these studies, with an elevation in liver function tests being the most common abnormality associated with the drug, which inhibits tumor necrosis factor alpha. Investigators noted no deaths, cases of tuberculosis, or other opportunistic infections among the patients taking infliximab in these studies.

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

SAN ANTONIO — Adding the selective costimulatory modulator abatacept to methotrexate in patients with rheumatoid arthritis who do not respond adequately to methotrexate alone resulted in “robust clinical efficacy” that persisted for 2 years, according to the findings of an extension study.

Among patients who completed 2 years of treatment, response rates were similar at 2 years to what they were at 1 year, Joel M. Kremer, M.D., said in a poster session at the annual meeting of the American College of Rheumatology. (See chart.)

In the initial double-blind phase of the trial, 115 participants whose mean age was 55.6 years and whose mean disease duration was 10 years were randomized to receive intravenous abatacept (10 mg/kg monthly) plus methotrexate in a stable dose of 10 to 30 mg/week for 1 year.

Those who completed the yearlong blinded phase were eligible to enroll in the long-term open trial, which used a fixed dose of abatacept (about 10 mg/kg) along with methotrexate.

A total of 84 patients entered the open phase and 75 completed the full 2 years. High rates of retention in the trial, along with improved ACR scores, demonstrated consistent and sustained clinical efficacy, said Dr. Kremer, director of research at the Center for Rheumatology, Albany, N.Y.

In addition to the standard American College of Rheumatology (ACR) 20, 50, and 70 responses, ACR 90 responses were assessed. This score was achieved by more than 13% of patients at year 1 and almost 15% at year 2.

During the double-blind phase of the study, the most common adverse events were nasopharyngitis, headache, nausea, and cough. There were no new emerging safety issues during the long-term extension phase, he said.

Abatacept is the first in a new class of agents that inhibit the full activation of T cells. It blocks the engagement of the costimulatory molecule CD28, resulting in the inhibition of cytokines that activate inflammatory cells.

Dr. Kremer disclosed that he receives research grants and consulting fees from multiple sponsors, including Bristol-Myers Squibb Co., the manufacturer of abatacept.

PARIS — Combining agents with complementary mechanisms and pharmacokinetic profiles may hold promise even for patients with severe psoriatic arthritis who have been failed by every other form of therapy.

German researchers used that approach, combining leflunomide (Arava) and etanercept (Enbrel) in two severely affected patients, with excellent results.

Jochen Schmitt, M.D., and Gottfried Wozel, M.D., of the department of dermatology at University Hospital Carl Gustav Carus of Dresden University of Technology presented their findings at the European Congress on Psoriasis 2004.

Confronted with patients who had severe swollen and tender joints, extensive psoriatic plaques, and profoundly affected quality of life and for whom an array of therapeutic options had failed, they decided to combine leflunomide and etanercept.

“The rationale of the combination is based on the predominant role of T cells and proinflammatory cytokines such as TNF-α in the pathogenesis of psoriasis,” they noted in a poster presentation.

“The active metabolite of leflunomide interferes with T-cell proliferation by inhibition of dihydroorotate dehydrogenase, a key enzyme of pyrimidine de novo synthesis,” and etanercept, a TNF-αreceptor, P75 fusion protein, blocks biologic activity to TNF-αaccording to the investigators.

Leflunomide was prescribed at an initial dosage of 100 mg for 3 days, then tapered to 20 mg and then to 10 mg. Patients received etanercept in 25-mg, twice-weekly subcutaneous injections.

The response was dramatic during the course of the 8-week study period and a follow-up period that extended 20 more weeks. The first patient went from 32 swollen and 30 tender joints, a Psoriasis Area and Severity Index (PASI) score of 52.6; and a Dermatology Life Quality Assessment score (DLQI) of 19, to 9 swollen and 8 tender joints, a PASI score of 1.8, and a DLQI score of 3.

The second patient was less severely affected at baseline but exhibited a complete remission. Specifically, she went from nine swollen and nine tender joints to zero; her PASI score dropped from 17.6 to 0, and her DLQI score declined from 3 to 0.

The researchers commented on the two drugs' complementary pharmacokinetic profiles.

“Leflunomide's active metabolite exhibits an extremely long half-life in vivo. Etanercept features an early onset of efficacy. Thus, in severe psoriasis, it might be reasonable to use leflunomide as a basic agent and to add etanercept when a relapse occurs,” Dr. Schmitt said.

PARIS — Combining agents with complementary mechanisms and pharmacokinetic profiles may hold promise even for patients with severe psoriatic arthritis who have been failed by every other form of therapy.

German researchers used that approach, combining leflunomide (Arava) and etanercept (Enbrel) in two severely affected patients, with excellent results.

Jochen Schmitt, M.D., and Gottfried Wozel, M.D., of the department of dermatology at University Hospital Carl Gustav Carus of Dresden University of Technology presented their findings at the European Congress on Psoriasis 2004.

Confronted with patients who had severe swollen and tender joints, extensive psoriatic plaques, and profoundly affected quality of life and for whom an array of therapeutic options had failed, they decided to combine leflunomide and etanercept.

“The rationale of the combination is based on the predominant role of T cells and proinflammatory cytokines such as TNF-α in the pathogenesis of psoriasis,” they noted in a poster presentation.

“The active metabolite of leflunomide interferes with T-cell proliferation by inhibition of dihydroorotate dehydrogenase, a key enzyme of pyrimidine de novo synthesis,” and etanercept, a TNF-αreceptor, P75 fusion protein, blocks biologic activity to TNF-αaccording to the investigators.

Leflunomide was prescribed at an initial dosage of 100 mg for 3 days, then tapered to 20 mg and then to 10 mg. Patients received etanercept in 25-mg, twice-weekly subcutaneous injections.

The response was dramatic during the course of the 8-week study period and a follow-up period that extended 20 more weeks. The first patient went from 32 swollen and 30 tender joints, a Psoriasis Area and Severity Index (PASI) score of 52.6; and a Dermatology Life Quality Assessment score (DLQI) of 19, to 9 swollen and 8 tender joints, a PASI score of 1.8, and a DLQI score of 3.

The second patient was less severely affected at baseline but exhibited a complete remission. Specifically, she went from nine swollen and nine tender joints to zero; her PASI score dropped from 17.6 to 0, and her DLQI score declined from 3 to 0.

The researchers commented on the two drugs' complementary pharmacokinetic profiles.

“Leflunomide's active metabolite exhibits an extremely long half-life in vivo. Etanercept features an early onset of efficacy. Thus, in severe psoriasis, it might be reasonable to use leflunomide as a basic agent and to add etanercept when a relapse occurs,” Dr. Schmitt said.

PARIS — Combining agents with complementary mechanisms and pharmacokinetic profiles may hold promise even for patients with severe psoriatic arthritis who have been failed by every other form of therapy.

German researchers used that approach, combining leflunomide (Arava) and etanercept (Enbrel) in two severely affected patients, with excellent results.

Jochen Schmitt, M.D., and Gottfried Wozel, M.D., of the department of dermatology at University Hospital Carl Gustav Carus of Dresden University of Technology presented their findings at the European Congress on Psoriasis 2004.

Confronted with patients who had severe swollen and tender joints, extensive psoriatic plaques, and profoundly affected quality of life and for whom an array of therapeutic options had failed, they decided to combine leflunomide and etanercept.

“The rationale of the combination is based on the predominant role of T cells and proinflammatory cytokines such as TNF-α in the pathogenesis of psoriasis,” they noted in a poster presentation.

“The active metabolite of leflunomide interferes with T-cell proliferation by inhibition of dihydroorotate dehydrogenase, a key enzyme of pyrimidine de novo synthesis,” and etanercept, a TNF-αreceptor, P75 fusion protein, blocks biologic activity to TNF-αaccording to the investigators.

Leflunomide was prescribed at an initial dosage of 100 mg for 3 days, then tapered to 20 mg and then to 10 mg. Patients received etanercept in 25-mg, twice-weekly subcutaneous injections.

The response was dramatic during the course of the 8-week study period and a follow-up period that extended 20 more weeks. The first patient went from 32 swollen and 30 tender joints, a Psoriasis Area and Severity Index (PASI) score of 52.6; and a Dermatology Life Quality Assessment score (DLQI) of 19, to 9 swollen and 8 tender joints, a PASI score of 1.8, and a DLQI score of 3.

The second patient was less severely affected at baseline but exhibited a complete remission. Specifically, she went from nine swollen and nine tender joints to zero; her PASI score dropped from 17.6 to 0, and her DLQI score declined from 3 to 0.

The researchers commented on the two drugs' complementary pharmacokinetic profiles.

“Leflunomide's active metabolite exhibits an extremely long half-life in vivo. Etanercept features an early onset of efficacy. Thus, in severe psoriasis, it might be reasonable to use leflunomide as a basic agent and to add etanercept when a relapse occurs,” Dr. Schmitt said.

BUDAPEST, HUNGARY — Infliximab, in combination with methotrexate, shows promising results in reducing the severity of psoriatic spondyloarthropathy, based on the results of a 2-year open-label study presented at the 4th International Congress on Autoimmunity.

Most of the 16 patients in the study showed improvement on several measures, according to Juan J. Scali, M.D., of Durand Hospital, Buenos Aires.

The patients in the study—nine men and seven women with a mean age of 38 years—had severe manifestations of the disease, little or no response to methotrexate, and a mean disease duration of 16 years. Seven patients were positive for HLA-B27, which is associated with ankylosing spondylitis.

Patients were given 5 mg of infliximab (Remicade) per kg of body weight as an intravenous infusion at baseline, at 2 and 6 weeks, and then once a month. They were continued on methotrexate 15 mg/wk.

Patients were evaluated using the psoriatic arthritis response criteria (PsARC) and the American College of Rheumatology (ACR) response criteria (20, 50, and 70). With PsARC, a patient must show improvement in two of the four measures—at least 30% reduction of tender joint count, at least a 30% reduction of swollen joint count, a decrease of at least 1 point on the physician global assessment, and a decrease of at least 1 point on the patient global assessment on a visual analog scale—to be a considered a responder. When the ACR response criteria are used, the patient must show a 20%, 50%, or 70% improvement in tender joint count, swollen joint count, and three of five other measures—patient assessment, physician assessment, erythrocyte sedimentation rate, pain scale, or functional questionnaire.

At the end of 24 months, 88%, 56%, and 31% of patients responded to treatment using the ACR 20, 50, and 70. With PsARC, 88% of patients had improvement at the end of the first year and 74% at the end of the second year.

Psoriasis activity was also measured using the Psoriasis Area and Severity Index (PASI). Patients were considered to have active disease with a PASI score of 16 or greater. At 1 year, 90% of patients showed an improvement in PASI scores, which dropped to 80% at 2 years. Also, 70% of patients had a favorable opinion of their response at the end of 2 years. Infliximab had good safety overall; no patients had allergic reactions or adverse events, he said.

Dr. Scali noted that the best results were seen at around 20 months. He recommended 6–12 months of infliximab therapy, followed by methotrexate alone.

BUDAPEST, HUNGARY — Infliximab, in combination with methotrexate, shows promising results in reducing the severity of psoriatic spondyloarthropathy, based on the results of a 2-year open-label study presented at the 4th International Congress on Autoimmunity.

Most of the 16 patients in the study showed improvement on several measures, according to Juan J. Scali, M.D., of Durand Hospital, Buenos Aires.

The patients in the study—nine men and seven women with a mean age of 38 years—had severe manifestations of the disease, little or no response to methotrexate, and a mean disease duration of 16 years. Seven patients were positive for HLA-B27, which is associated with ankylosing spondylitis.

Patients were given 5 mg of infliximab (Remicade) per kg of body weight as an intravenous infusion at baseline, at 2 and 6 weeks, and then once a month. They were continued on methotrexate 15 mg/wk.

Patients were evaluated using the psoriatic arthritis response criteria (PsARC) and the American College of Rheumatology (ACR) response criteria (20, 50, and 70). With PsARC, a patient must show improvement in two of the four measures—at least 30% reduction of tender joint count, at least a 30% reduction of swollen joint count, a decrease of at least 1 point on the physician global assessment, and a decrease of at least 1 point on the patient global assessment on a visual analog scale—to be a considered a responder. When the ACR response criteria are used, the patient must show a 20%, 50%, or 70% improvement in tender joint count, swollen joint count, and three of five other measures—patient assessment, physician assessment, erythrocyte sedimentation rate, pain scale, or functional questionnaire.

At the end of 24 months, 88%, 56%, and 31% of patients responded to treatment using the ACR 20, 50, and 70. With PsARC, 88% of patients had improvement at the end of the first year and 74% at the end of the second year.

Psoriasis activity was also measured using the Psoriasis Area and Severity Index (PASI). Patients were considered to have active disease with a PASI score of 16 or greater. At 1 year, 90% of patients showed an improvement in PASI scores, which dropped to 80% at 2 years. Also, 70% of patients had a favorable opinion of their response at the end of 2 years. Infliximab had good safety overall; no patients had allergic reactions or adverse events, he said.

Dr. Scali noted that the best results were seen at around 20 months. He recommended 6–12 months of infliximab therapy, followed by methotrexate alone.

BUDAPEST, HUNGARY — Infliximab, in combination with methotrexate, shows promising results in reducing the severity of psoriatic spondyloarthropathy, based on the results of a 2-year open-label study presented at the 4th International Congress on Autoimmunity.

Most of the 16 patients in the study showed improvement on several measures, according to Juan J. Scali, M.D., of Durand Hospital, Buenos Aires.

The patients in the study—nine men and seven women with a mean age of 38 years—had severe manifestations of the disease, little or no response to methotrexate, and a mean disease duration of 16 years. Seven patients were positive for HLA-B27, which is associated with ankylosing spondylitis.

Patients were given 5 mg of infliximab (Remicade) per kg of body weight as an intravenous infusion at baseline, at 2 and 6 weeks, and then once a month. They were continued on methotrexate 15 mg/wk.

Patients were evaluated using the psoriatic arthritis response criteria (PsARC) and the American College of Rheumatology (ACR) response criteria (20, 50, and 70). With PsARC, a patient must show improvement in two of the four measures—at least 30% reduction of tender joint count, at least a 30% reduction of swollen joint count, a decrease of at least 1 point on the physician global assessment, and a decrease of at least 1 point on the patient global assessment on a visual analog scale—to be a considered a responder. When the ACR response criteria are used, the patient must show a 20%, 50%, or 70% improvement in tender joint count, swollen joint count, and three of five other measures—patient assessment, physician assessment, erythrocyte sedimentation rate, pain scale, or functional questionnaire.

At the end of 24 months, 88%, 56%, and 31% of patients responded to treatment using the ACR 20, 50, and 70. With PsARC, 88% of patients had improvement at the end of the first year and 74% at the end of the second year.

Psoriasis activity was also measured using the Psoriasis Area and Severity Index (PASI). Patients were considered to have active disease with a PASI score of 16 or greater. At 1 year, 90% of patients showed an improvement in PASI scores, which dropped to 80% at 2 years. Also, 70% of patients had a favorable opinion of their response at the end of 2 years. Infliximab had good safety overall; no patients had allergic reactions or adverse events, he said.

Dr. Scali noted that the best results were seen at around 20 months. He recommended 6–12 months of infliximab therapy, followed by methotrexate alone.

CHICAGO — Baseline plasma matrix metalloproteinase 3 levels predicted joint space narrowing over 16 months in patients with knee osteoarthritis, according to findings from a pilot study.

However, the predictive accuracy of MMP-3 declines somewhat between 16 months and 30 months, Steve A. Mazzuca, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

MMP-3, which is produced by chondrocytes and synoviocytes, has been implicated in the degradation of articular cartilage in osteoarthritis (OA). Compared with healthy subjects, patients with knee OA have higher concentrations of MMP-3 in their synovial fluid and blood.

“We are unable to answer the question right now if MMP-3 is an adequate surrogate for joint space narrowing, but it does correlate in real time,” said Dr. Mazzuca, professor and senior scientist at Indiana University, Indianapolis.

The 30-month study, led by Stefan Lohmander, M.D., of Lund (Sweden) University, involved 120 obese women 45–64 years old with unilateral knee OA.

Study participants were selected from a larger randomized trial of doxycycline, a disease-modifying OA drug. An equal number of patients had progressive radiographic knee OA and stable disease.

During the follow-up period, mean joint space narrowing in the index knee was 0.97 mm among those with progressive disease. There was the slightest increase, 0.03 mm, in joint space width in those with stable disease.

After adjustment for age, baseline joint space width, and treatment, a regression analysis showed that patients with the highest MMP-3 concentrations at baseline (more than 11.85 ng/mL) were more than three times as likely to progress to joint space narrowing in both knees at 16 months than patients with the lowest MMP-3 concentrations (1.5 ng/mL to 6.42 ng/mL) at baseline (odds ratio 3.48).

The association was less striking at 30 months, although the risk of progression remained significantly higher among patients with the highest MMP-3 levels (OR 2.09), Dr. Mazzuca reported at the congress, sponsored by the Osteoarthritis Research Society International.

The study also evaluated whether plasma MMP-3 values could have served as a surrogate marker in the original doxycycline trial. Serial MMP-3 levels examined at two time intervals (0–16 months and 16–30 months) found that both mean and maximal MMP-3 levels were significantly related to joint space narrowing in patients treated with placebo. For the doxycycline group, there was not a significant association at the first time interval, and a reverse association at the second interval. Dr. Mazzuca concluded that serum MMP-3 correlates with concurrent joint space narrowing in knees not treated with doxycycline.

CHICAGO — Baseline plasma matrix metalloproteinase 3 levels predicted joint space narrowing over 16 months in patients with knee osteoarthritis, according to findings from a pilot study.

However, the predictive accuracy of MMP-3 declines somewhat between 16 months and 30 months, Steve A. Mazzuca, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

MMP-3, which is produced by chondrocytes and synoviocytes, has been implicated in the degradation of articular cartilage in osteoarthritis (OA). Compared with healthy subjects, patients with knee OA have higher concentrations of MMP-3 in their synovial fluid and blood.

“We are unable to answer the question right now if MMP-3 is an adequate surrogate for joint space narrowing, but it does correlate in real time,” said Dr. Mazzuca, professor and senior scientist at Indiana University, Indianapolis.

The 30-month study, led by Stefan Lohmander, M.D., of Lund (Sweden) University, involved 120 obese women 45–64 years old with unilateral knee OA.

Study participants were selected from a larger randomized trial of doxycycline, a disease-modifying OA drug. An equal number of patients had progressive radiographic knee OA and stable disease.

During the follow-up period, mean joint space narrowing in the index knee was 0.97 mm among those with progressive disease. There was the slightest increase, 0.03 mm, in joint space width in those with stable disease.

After adjustment for age, baseline joint space width, and treatment, a regression analysis showed that patients with the highest MMP-3 concentrations at baseline (more than 11.85 ng/mL) were more than three times as likely to progress to joint space narrowing in both knees at 16 months than patients with the lowest MMP-3 concentrations (1.5 ng/mL to 6.42 ng/mL) at baseline (odds ratio 3.48).

The association was less striking at 30 months, although the risk of progression remained significantly higher among patients with the highest MMP-3 levels (OR 2.09), Dr. Mazzuca reported at the congress, sponsored by the Osteoarthritis Research Society International.

The study also evaluated whether plasma MMP-3 values could have served as a surrogate marker in the original doxycycline trial. Serial MMP-3 levels examined at two time intervals (0–16 months and 16–30 months) found that both mean and maximal MMP-3 levels were significantly related to joint space narrowing in patients treated with placebo. For the doxycycline group, there was not a significant association at the first time interval, and a reverse association at the second interval. Dr. Mazzuca concluded that serum MMP-3 correlates with concurrent joint space narrowing in knees not treated with doxycycline.

CHICAGO — Baseline plasma matrix metalloproteinase 3 levels predicted joint space narrowing over 16 months in patients with knee osteoarthritis, according to findings from a pilot study.

However, the predictive accuracy of MMP-3 declines somewhat between 16 months and 30 months, Steve A. Mazzuca, Ph.D., reported at the 2004 World Congress on Osteoarthritis.

MMP-3, which is produced by chondrocytes and synoviocytes, has been implicated in the degradation of articular cartilage in osteoarthritis (OA). Compared with healthy subjects, patients with knee OA have higher concentrations of MMP-3 in their synovial fluid and blood.

“We are unable to answer the question right now if MMP-3 is an adequate surrogate for joint space narrowing, but it does correlate in real time,” said Dr. Mazzuca, professor and senior scientist at Indiana University, Indianapolis.

The 30-month study, led by Stefan Lohmander, M.D., of Lund (Sweden) University, involved 120 obese women 45–64 years old with unilateral knee OA.

Study participants were selected from a larger randomized trial of doxycycline, a disease-modifying OA drug. An equal number of patients had progressive radiographic knee OA and stable disease.

During the follow-up period, mean joint space narrowing in the index knee was 0.97 mm among those with progressive disease. There was the slightest increase, 0.03 mm, in joint space width in those with stable disease.

After adjustment for age, baseline joint space width, and treatment, a regression analysis showed that patients with the highest MMP-3 concentrations at baseline (more than 11.85 ng/mL) were more than three times as likely to progress to joint space narrowing in both knees at 16 months than patients with the lowest MMP-3 concentrations (1.5 ng/mL to 6.42 ng/mL) at baseline (odds ratio 3.48).

The association was less striking at 30 months, although the risk of progression remained significantly higher among patients with the highest MMP-3 levels (OR 2.09), Dr. Mazzuca reported at the congress, sponsored by the Osteoarthritis Research Society International.

The study also evaluated whether plasma MMP-3 values could have served as a surrogate marker in the original doxycycline trial. Serial MMP-3 levels examined at two time intervals (0–16 months and 16–30 months) found that both mean and maximal MMP-3 levels were significantly related to joint space narrowing in patients treated with placebo. For the doxycycline group, there was not a significant association at the first time interval, and a reverse association at the second interval. Dr. Mazzuca concluded that serum MMP-3 correlates with concurrent joint space narrowing in knees not treated with doxycycline.

CHICAGO — The association between knee pain and the presence of pathologic features varies by the different compartments of the knee, Kathryn Wildy, M.D., reported at the 2004 World Congress on Osteoarthritis.

Using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system, a semiquantitative method that systematically scores 11 structural features, including articular cartilage, subarticular marrow edema, cysts, and bone attrition in eight different locations in the knee, Dr. Wildy and colleagues demonstrated how MRI studies that show the worst pathologically affected compartment, or even the total knee, often fail to correspond to the pain.

“When you look at the total knee, you probably are losing the story. We're looking at each compartment, rather than just the worst compartment, and you need to look at the different regions within each compartment,” Dr. Wildy said at the meeting sponsored by the Osteoarthritis Research Society International.

In their multicenter study involving 263 elderly men and women with discordant knee pain, axial, coronal, and sagittal plane studies were obtained on fast spin echo MRI and the WORMS system was used to score pathologic features of the knee. The patient's nonpainful knee served as a control.

Knee pain was defined as pain on most days of the month in the past year or moderate pain on the Western Ontario and McMaster University Osteoarthritis (WOMAC) index in the past 30 days; the mean WOMAC score was 6.2 for the painful knee and 0.4 for the nonpainful knee.

In this community-based population, the severity of cartilage damage, osteophytes, and synovitis were each independently associated with knee pain, reported Dr. Wildy, who led the study while at the University of Pittsburgh.

In the medial tibiofemoral compartment, bone attrition and bone marrow edema scores greater than 0 were significantly associated with knee pain; in the lateral tibiofemoral compartment the presence of all measured features was significantly associated with pain.

In the patellofemoral compartment, no feature was associated with pain. For the total knee, cartilage damage, bone attrition, and bone marrow edema scores greater than 0 were associated with knee pain, said Dr. Wildy, who now practices in Omaha, Neb.

Interaction between features revealed that bone marrow edema, which was common in the painful knees, was significantly associated with pain when accompanied by high cartilage damage in either the total knee (OR 3.27) or the medial tibiofemoral compartment (OR 2.0).

CHICAGO — The association between knee pain and the presence of pathologic features varies by the different compartments of the knee, Kathryn Wildy, M.D., reported at the 2004 World Congress on Osteoarthritis.

Using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system, a semiquantitative method that systematically scores 11 structural features, including articular cartilage, subarticular marrow edema, cysts, and bone attrition in eight different locations in the knee, Dr. Wildy and colleagues demonstrated how MRI studies that show the worst pathologically affected compartment, or even the total knee, often fail to correspond to the pain.

“When you look at the total knee, you probably are losing the story. We're looking at each compartment, rather than just the worst compartment, and you need to look at the different regions within each compartment,” Dr. Wildy said at the meeting sponsored by the Osteoarthritis Research Society International.

In their multicenter study involving 263 elderly men and women with discordant knee pain, axial, coronal, and sagittal plane studies were obtained on fast spin echo MRI and the WORMS system was used to score pathologic features of the knee. The patient's nonpainful knee served as a control.

Knee pain was defined as pain on most days of the month in the past year or moderate pain on the Western Ontario and McMaster University Osteoarthritis (WOMAC) index in the past 30 days; the mean WOMAC score was 6.2 for the painful knee and 0.4 for the nonpainful knee.

In this community-based population, the severity of cartilage damage, osteophytes, and synovitis were each independently associated with knee pain, reported Dr. Wildy, who led the study while at the University of Pittsburgh.

In the medial tibiofemoral compartment, bone attrition and bone marrow edema scores greater than 0 were significantly associated with knee pain; in the lateral tibiofemoral compartment the presence of all measured features was significantly associated with pain.

In the patellofemoral compartment, no feature was associated with pain. For the total knee, cartilage damage, bone attrition, and bone marrow edema scores greater than 0 were associated with knee pain, said Dr. Wildy, who now practices in Omaha, Neb.

Interaction between features revealed that bone marrow edema, which was common in the painful knees, was significantly associated with pain when accompanied by high cartilage damage in either the total knee (OR 3.27) or the medial tibiofemoral compartment (OR 2.0).

CHICAGO — The association between knee pain and the presence of pathologic features varies by the different compartments of the knee, Kathryn Wildy, M.D., reported at the 2004 World Congress on Osteoarthritis.

Using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system, a semiquantitative method that systematically scores 11 structural features, including articular cartilage, subarticular marrow edema, cysts, and bone attrition in eight different locations in the knee, Dr. Wildy and colleagues demonstrated how MRI studies that show the worst pathologically affected compartment, or even the total knee, often fail to correspond to the pain.

“When you look at the total knee, you probably are losing the story. We're looking at each compartment, rather than just the worst compartment, and you need to look at the different regions within each compartment,” Dr. Wildy said at the meeting sponsored by the Osteoarthritis Research Society International.

In their multicenter study involving 263 elderly men and women with discordant knee pain, axial, coronal, and sagittal plane studies were obtained on fast spin echo MRI and the WORMS system was used to score pathologic features of the knee. The patient's nonpainful knee served as a control.

Knee pain was defined as pain on most days of the month in the past year or moderate pain on the Western Ontario and McMaster University Osteoarthritis (WOMAC) index in the past 30 days; the mean WOMAC score was 6.2 for the painful knee and 0.4 for the nonpainful knee.

In this community-based population, the severity of cartilage damage, osteophytes, and synovitis were each independently associated with knee pain, reported Dr. Wildy, who led the study while at the University of Pittsburgh.

In the medial tibiofemoral compartment, bone attrition and bone marrow edema scores greater than 0 were significantly associated with knee pain; in the lateral tibiofemoral compartment the presence of all measured features was significantly associated with pain.

In the patellofemoral compartment, no feature was associated with pain. For the total knee, cartilage damage, bone attrition, and bone marrow edema scores greater than 0 were associated with knee pain, said Dr. Wildy, who now practices in Omaha, Neb.

Interaction between features revealed that bone marrow edema, which was common in the painful knees, was significantly associated with pain when accompanied by high cartilage damage in either the total knee (OR 3.27) or the medial tibiofemoral compartment (OR 2.0).

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Current hormone therapy use in postmenopausal women reduces cartilage turnover, Joanne M. Jordan, M.D., said at the 2004 World Congress on Osteoarthritis.

The study included 168 postmenopausal women, of whom 49% were African American, 23% were current hormone therapy (HT) users, and 63% had knee osteoarthritis (OA).

Rates of type II collagen cleavage measured by levels of the cartilage degradation assay and collagen II synthesis measured by type II procollagen (CPII) synthesis were lower in current HT users than in nonusers.

Taken together, these results demonstrate reduced collagen II turnover in HT users with and without osteoarthritis, Dr. Jordan reported in a poster at the meeting, sponsored by the Osteoarthritis Research Society International.

Dr. Jordan and colleagues at the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill previously reported that current HT use is associated with lower levels of serum cartilage oligomeric matrix protein, another marker of cartilage degradation.

In the current study, led by doctoral student Anca D. Dragomir, separate analyses of covariance models were used to evaluate the relationship between current HRT use and biomarker levels.

After controlling for ethnicity, age, body mass index, and knee OA status, only the reduction in mean CPII associated with current HT use was significantly associated with collagen II synthesis.

There was evidence of an association between current HT use and knee OA status for another biomarker, chondroitin sulphate epitope 846 (CSE 846), thought to be a marker of newly synthesized cartilage proteoglycan. HT users without OA had higher levels of CSE 846, compared with HT users with OA. This suggests that HT use could increase proteoglycan aggrecan production in postmenopausal women with no radiographic evidence of knee or hip OA.

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden

CHICAGO — Tidal irrigation leads to more sustained benefits than intraarticular corticosteroid injections in patients with knee osteoarthritis, particularly in those without an effusion, Nigel K. Arden, M.D., said at the 2004 World Congress on Osteoarthritis.

Both treatments significantly improved pain and function at 2 weeks, according to results from a randomized, single-blinded, parallel group trial involving patients with symptomatic knee OA. But the benefits were maintained only in the irrigation group at 26 weeks.

Tidal irrigation, which involves infusing saline into the knee under local anesthesia to repeatedly distend the capsule, is thought to provide benefit by disrupting intraarticular adhesions and by cleansing away debris and inflammatory cytokines, said Dr. Arden of Southampton (England) University Hospitals NHS Trust.

The 150 study participants were randomized to intraarticular corticosteroid injections with 40 mg triamcinolone and 2 mL of 1% lidocaine or irrigation of the knee with 500–1,000 mL of normal saline.

At 2 weeks, pain scores had improved significantly from baseline, and there were no significant differences between treatment groups. The mean pain score for both groups was 243 at baseline, on a 0–500 scale. At 2 weeks scores fell to 168 in the steroid group and 155 in the irrigation group. At 26 weeks, significant pain relief was maintained only in the irrigation group (mean 173 vs. 232 for the steroid group). A similar pattern was seen for function at 26 weeks.

At baseline, 61% of patients had an effusion, and at 2 weeks' follow-up, there was little difference between treatment groups in this subset of patients.

By 26 weeks, however, only patients treated with tidal irrigation had significant improvement, and this was more marked in patients without an effusion.

Among patients without an effusion, the mean pain score for those treated with irrigation was 164 vs. 262 for patients treated with injections. Among patients with an effusion, the mean pain score for those treated with irrigation was 180 vs. 214 for patients treated with injections.

Patients' overall assessment of treatment was similar at 2 weeks' and 4 weeks' follow-up. But patients' self-assessments significantly favored tidal irrigation at 12 and 24 weeks, Dr. Arden said at the meeting, sponsored by the Osteoarthritis Research Society International.

Such findings in no way account for the placebo effect of the interventions, John D. Bradley, M.D., told this newspaper. Generally, “the more elaborate the intervention, the more potent the placebo effect.”

In their investigation, Dr. Bradley and colleagues at Indiana University, Indianapolis, tracked 180 randomized subjects with knee OA for up to 12 months following randomization to tidal irrigation or a sham procedure, which involved placement of a needle through the soft tissue and down to, but not through, the joint capsule. Both groups received intraarticular anesthesia with bupivacaine.

The investigators concluded that after adjusting for baseline differences between groups, there were no differences between outcomes from the real and the sham procedures (Arthritis Rheum. 2002; 46:100–8).

Dr. Bradley noted that psychological factors and the subjects' guesses regarding the identity of their treatment correlated with their response to treatment.

The controversial procedure is thought to disrupt intraarticular adhesions, and clear away debris and inflammatory cytokines. Courtesy Dr. Nigel K. Arden