Rheumatoid Arthritis

CHICAGO — The cardiovascular risk of celecoxib is a function of both dose and dosing schedule, as well as a patient's baseline cardiovascular risk, according to a new National Cancer Institute-sponsored pooled analysis of six randomized trials.

Individuals at higher baseline cardiovascular risk, according to the Framingham risk score, had substantially higher relative as well as absolute risk of celecoxib-related cardiovascular events than did those patients at low baseline risk, Dr. Scott D. Solomon explained at the annual meeting of the American College of Cardiology.

“These data should help guide rational clinical decisions regarding celecoxib use,” said Dr. Solomon of the Brigham and Women's Hospital, Boston.

“The data may provide a measure of confidence in prescribing celecoxib in patients with very low baseline cardiovascular risk, but would argue for caution in prescribing celecoxib in patients with high baseline cardiovascular risk,” Dr. Solomon commented.

Of the dosing regimens evaluated in the pooled analysis, 400 mg once daily was associated with a significantly lower event rate than was 200 mg b.i.d., which in turn was safer than 400 mg b.i.d., the cardiologist added.

Dr. Solomon presented the results of the Cross Trial Safety Analysis, involving 7,950 patients with 16,070 patient-years of follow-up in six placebo-controlled trials.

All of the trials investigated celecoxib for conditions other than arthritis.

Three studies evaluated the cyclooxygenase-2 (COX-2)-selective NSAID for secondary prevention of colonic polyps; the others involved degenerative eye disease, secondary prevention of breast cancer, and prevention of Alzheimer's disease.

All but one study was sponsored by the NIH.

The rate of the primary study end point—the combination of cardiovascular death, MI, stroke, heart failure, or a thromboembolic event—was 1.1-fold greater in patients on 400 mg of celecoxib once daily than in those on placebo, 1.8-fold greater in patients on 200 mg b.i.d., and 3.1-fold greater in those on 400 mg b.i.d.

The cardiovascular risk associated with the COX-2 inhibitor was unaffected by concomitant use of low-dose aspirin.

The event rate associated with 400 mg of celecoxib once daily wasn't significantly different than with placebo.

However, there were relatively few cardiovascular events in patients on this regimen, making for wide confidence intervals.

Thus, it was theoretically possible that 400 mg once daily was associated with anything from a 40% reduction in cardiovascular events to a twofold increase, Dr. Solomon noted.

Why did celecoxib at 200 mg b.i.d. carry a significantly higher event rate than did 400 mg once daily? The leading hypothesis involves the fact that the drug suppresses prostacyclin for about 12 hours.

Once-daily dosing thus provides the arteries with a respite from the drug's effects, he said.

All doses studied in the analysis are substantially higher than the 200-mg, once daily dosage for which 80%–90% of all celecoxib prescriptions are written. That's the standard dosage in osteoarthritis. But the higher doses are routinely used for patients with rheumatoid arthritis, familial adenomatous polyposis, and acute pain and dysmenorrhea.

The study findings raise the question of whether celecoxib should ever be given to patients with coronary heart disease, or diabetes (considered a CHD risk factor), or rheumatoid arthritis (which is drawing increasing attention as a possible new CHD risk factor).

The trouble with issuing a blanket prohibition in these circumstances, Dr. Solomon said, is that patients who require pain relief have to take something—and it's unclear whether conventional NSAIDs are safer.

Indeed, celecoxib's black box warning states, “All NSAIDs may have a similar risk.”

The answer to that key question is expected to come from the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial. PRECISION is an ongoing Pfizer Inc.-sponsored randomized trial involving 21,000 patients with osteoarthritis or rheumatoid arthritis with, or at increased risk for, cardiovascular disease.

The end points are symptom relief and cardiovascular, renal, and GI safety. The celecoxib dosage is 200 mg once daily, with some patients being titrated to b.i.d. therapy.

“I am a little bit reassured by the data [in the pooled analysis] with the 400-mg once-a-day dose,” commented PRECISION principal investigator Dr. Stephen Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation.

The data 'should help guide rational clinical decisions regarding celecoxib use.' DR. SOLOMON

CHICAGO — The cardiovascular risk of celecoxib is a function of both dose and dosing schedule, as well as a patient's baseline cardiovascular risk, according to a new National Cancer Institute-sponsored pooled analysis of six randomized trials.

Individuals at higher baseline cardiovascular risk, according to the Framingham risk score, had substantially higher relative as well as absolute risk of celecoxib-related cardiovascular events than did those patients at low baseline risk, Dr. Scott D. Solomon explained at the annual meeting of the American College of Cardiology.

“These data should help guide rational clinical decisions regarding celecoxib use,” said Dr. Solomon of the Brigham and Women's Hospital, Boston.

“The data may provide a measure of confidence in prescribing celecoxib in patients with very low baseline cardiovascular risk, but would argue for caution in prescribing celecoxib in patients with high baseline cardiovascular risk,” Dr. Solomon commented.

Of the dosing regimens evaluated in the pooled analysis, 400 mg once daily was associated with a significantly lower event rate than was 200 mg b.i.d., which in turn was safer than 400 mg b.i.d., the cardiologist added.

Dr. Solomon presented the results of the Cross Trial Safety Analysis, involving 7,950 patients with 16,070 patient-years of follow-up in six placebo-controlled trials.

All of the trials investigated celecoxib for conditions other than arthritis.

Three studies evaluated the cyclooxygenase-2 (COX-2)-selective NSAID for secondary prevention of colonic polyps; the others involved degenerative eye disease, secondary prevention of breast cancer, and prevention of Alzheimer's disease.

All but one study was sponsored by the NIH.

The rate of the primary study end point—the combination of cardiovascular death, MI, stroke, heart failure, or a thromboembolic event—was 1.1-fold greater in patients on 400 mg of celecoxib once daily than in those on placebo, 1.8-fold greater in patients on 200 mg b.i.d., and 3.1-fold greater in those on 400 mg b.i.d.

The cardiovascular risk associated with the COX-2 inhibitor was unaffected by concomitant use of low-dose aspirin.

The event rate associated with 400 mg of celecoxib once daily wasn't significantly different than with placebo.

However, there were relatively few cardiovascular events in patients on this regimen, making for wide confidence intervals.

Thus, it was theoretically possible that 400 mg once daily was associated with anything from a 40% reduction in cardiovascular events to a twofold increase, Dr. Solomon noted.

Why did celecoxib at 200 mg b.i.d. carry a significantly higher event rate than did 400 mg once daily? The leading hypothesis involves the fact that the drug suppresses prostacyclin for about 12 hours.

Once-daily dosing thus provides the arteries with a respite from the drug's effects, he said.

All doses studied in the analysis are substantially higher than the 200-mg, once daily dosage for which 80%–90% of all celecoxib prescriptions are written. That's the standard dosage in osteoarthritis. But the higher doses are routinely used for patients with rheumatoid arthritis, familial adenomatous polyposis, and acute pain and dysmenorrhea.

The study findings raise the question of whether celecoxib should ever be given to patients with coronary heart disease, or diabetes (considered a CHD risk factor), or rheumatoid arthritis (which is drawing increasing attention as a possible new CHD risk factor).

The trouble with issuing a blanket prohibition in these circumstances, Dr. Solomon said, is that patients who require pain relief have to take something—and it's unclear whether conventional NSAIDs are safer.

Indeed, celecoxib's black box warning states, “All NSAIDs may have a similar risk.”

The answer to that key question is expected to come from the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial. PRECISION is an ongoing Pfizer Inc.-sponsored randomized trial involving 21,000 patients with osteoarthritis or rheumatoid arthritis with, or at increased risk for, cardiovascular disease.

The end points are symptom relief and cardiovascular, renal, and GI safety. The celecoxib dosage is 200 mg once daily, with some patients being titrated to b.i.d. therapy.

“I am a little bit reassured by the data [in the pooled analysis] with the 400-mg once-a-day dose,” commented PRECISION principal investigator Dr. Stephen Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation.

The data 'should help guide rational clinical decisions regarding celecoxib use.' DR. SOLOMON

CHICAGO — The cardiovascular risk of celecoxib is a function of both dose and dosing schedule, as well as a patient's baseline cardiovascular risk, according to a new National Cancer Institute-sponsored pooled analysis of six randomized trials.

Individuals at higher baseline cardiovascular risk, according to the Framingham risk score, had substantially higher relative as well as absolute risk of celecoxib-related cardiovascular events than did those patients at low baseline risk, Dr. Scott D. Solomon explained at the annual meeting of the American College of Cardiology.

“These data should help guide rational clinical decisions regarding celecoxib use,” said Dr. Solomon of the Brigham and Women's Hospital, Boston.

“The data may provide a measure of confidence in prescribing celecoxib in patients with very low baseline cardiovascular risk, but would argue for caution in prescribing celecoxib in patients with high baseline cardiovascular risk,” Dr. Solomon commented.

Of the dosing regimens evaluated in the pooled analysis, 400 mg once daily was associated with a significantly lower event rate than was 200 mg b.i.d., which in turn was safer than 400 mg b.i.d., the cardiologist added.

Dr. Solomon presented the results of the Cross Trial Safety Analysis, involving 7,950 patients with 16,070 patient-years of follow-up in six placebo-controlled trials.

All of the trials investigated celecoxib for conditions other than arthritis.

Three studies evaluated the cyclooxygenase-2 (COX-2)-selective NSAID for secondary prevention of colonic polyps; the others involved degenerative eye disease, secondary prevention of breast cancer, and prevention of Alzheimer's disease.

All but one study was sponsored by the NIH.

The rate of the primary study end point—the combination of cardiovascular death, MI, stroke, heart failure, or a thromboembolic event—was 1.1-fold greater in patients on 400 mg of celecoxib once daily than in those on placebo, 1.8-fold greater in patients on 200 mg b.i.d., and 3.1-fold greater in those on 400 mg b.i.d.

The cardiovascular risk associated with the COX-2 inhibitor was unaffected by concomitant use of low-dose aspirin.

The event rate associated with 400 mg of celecoxib once daily wasn't significantly different than with placebo.

However, there were relatively few cardiovascular events in patients on this regimen, making for wide confidence intervals.

Thus, it was theoretically possible that 400 mg once daily was associated with anything from a 40% reduction in cardiovascular events to a twofold increase, Dr. Solomon noted.

Why did celecoxib at 200 mg b.i.d. carry a significantly higher event rate than did 400 mg once daily? The leading hypothesis involves the fact that the drug suppresses prostacyclin for about 12 hours.

Once-daily dosing thus provides the arteries with a respite from the drug's effects, he said.

All doses studied in the analysis are substantially higher than the 200-mg, once daily dosage for which 80%–90% of all celecoxib prescriptions are written. That's the standard dosage in osteoarthritis. But the higher doses are routinely used for patients with rheumatoid arthritis, familial adenomatous polyposis, and acute pain and dysmenorrhea.

The study findings raise the question of whether celecoxib should ever be given to patients with coronary heart disease, or diabetes (considered a CHD risk factor), or rheumatoid arthritis (which is drawing increasing attention as a possible new CHD risk factor).

The trouble with issuing a blanket prohibition in these circumstances, Dr. Solomon said, is that patients who require pain relief have to take something—and it's unclear whether conventional NSAIDs are safer.

Indeed, celecoxib's black box warning states, “All NSAIDs may have a similar risk.”

The answer to that key question is expected to come from the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial. PRECISION is an ongoing Pfizer Inc.-sponsored randomized trial involving 21,000 patients with osteoarthritis or rheumatoid arthritis with, or at increased risk for, cardiovascular disease.

The end points are symptom relief and cardiovascular, renal, and GI safety. The celecoxib dosage is 200 mg once daily, with some patients being titrated to b.i.d. therapy.

“I am a little bit reassured by the data [in the pooled analysis] with the 400-mg once-a-day dose,” commented PRECISION principal investigator Dr. Stephen Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation.

The data 'should help guide rational clinical decisions regarding celecoxib use.' DR. SOLOMON

NEW YORK — Increasing experience with the biologic agents in psoriatic arthritis is showing that these drugs are effective across all domains of this complex disease.

Tumor necrosis factor (TNF) inhibitors in particular have proven beneficial in the treatment of the peripheral arthritis, skin and nail disease, axial disease, dactylitis, and enthesitis associated with psoriatic arthritis (PsA).

Traditional disease-modifying antirheumatic drugs such as methotrexate, in contrast, may be useful for the arthritis and skin and nail disease, but are less effective for the other disease manifestations, according to Dr. Philip Mease, of the University of Washington, chief of rheumatology research, Swedish Medical Center, and head, Seattle Rheumatology Associates.

This difference in therapeutic efficacy may relate to important differences in pathophysiology between PsA and rheumatoid arthritis (RA).

For example, the synovitis in PsA is associated with less sublining infiltrate and with greater vascularity than in RA. There is also an increased expression of toll-like receptors 2 and 4 and an increased number of polymorphonuclear leukocytes, suggesting a greater role for the innate immune system and possibly microbial antigen stimulation, Dr. Mease said at a rheumatology meeting sponsored by New York University.

In PsA there also is a role for unique lineages of monocytes effector cells that differentiate into macrophages, osteoclasts, Langerhans cells, and dendritic cells via specific microenvironmental signals, he said.

Trials of anti-TNF drugs in PsA have permitted, but not required, both background methotrexate, nonsteroidal anti-inflammatories, and low-dose prednisone, and patients with oligoarticular disease have been included.

For infliximab, newly published 98-week data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) demonstrate a similar degree of sustained effectiveness.

In the open-label extension phase of the current trial, 62% of the 78 patients continuing on the drug at week 98 had achieved an American College of Rheumatology 20 (ACR20) response, while 45% and 35% had ACR50 and ACR70 responses, respectively.

Among those whose baseline PASI score was 2.5 or greater, 64% achieved a 75% improvement (J. Rheumatol., First Release March 15, 2008).

Similar results also have been seen with adalimumab, with 70% of patients reaching a PASI 75 response and improvements in disability being sustained out to week 48 (Arthritis Rheum. 2007;56:476–88).

For etanercept, 2-year data demonstrated sustained effectiveness in ACR scores over time and inhibition of progression of radiologic damage. Approximately 40% of patients achieved Psoriasis Area Severity Index (PASI) 75 responses (J. Rheumatol. 2006;33:712–21).

But unanswered questions remain regarding the use of anti-TNF drugs for PsA, such as whether additional benefits result from adding methotrexate, Dr. Mease said.

Because the trials thus far have been inconsistent as to whether background methotrexate was used, what is needed to answer this question is a trial that enrolls methotrexate-naive patients and randomizes them to methotrexate monotherapy, anti-TNF monotherapy, or the combination, he said.

“We also don't know what the impact of these drugs will be on PsA comorbidities,” he said.

RA registries are showing benefits in terms of cardiovascular outcomes, and this may also be the case in PsA. The answers will only come from sources such as the Consortium of Rheumatology Researchers of North America (CORRONA) database, which is collecting long-term data not only on outcomes in RA but also on PsA, osteoarthritis, and osteoporosis.

It also remains to be seen if other comorbidities associated with PsA will benefit from anti-TNF therapy, including infection, lymphoma, and depression.

“A further question is what we should do about patients who are inadequately responding to these anti-TNFs,” he said. A variety of other therapies are being assessed, including other anti-TNFs such as golimumab, intra-articular anti-TNF agents, other cytokine targets such as interleukin-12/interleukin-23, B-cell ablation with rituximab, and small molecules such as the JAK3 inhibitor.

Another new area of exploration in the spondylarthropathies is the use of anti-TNF drugs in preradiographic ankylosing spondylitis (AS), Dr. Mease noted.

In an open-label extension study of 22 patients with early axial spondylarthritis but without radiographic sacroiliitis, 46% of patients receiving adalimumab had a sustained 40% improvement in the Assessments in Ankylosing Spondylitis 40 (ASAS40) criteria (Ann. Rheum. Dis. 2007;66[suppl II]:64–5).

The impact of anti-TNF drugs on PsA comorbidities is unknown, but good CV outcomes are seen in RA registries. DR. MEASE

NEW YORK — Increasing experience with the biologic agents in psoriatic arthritis is showing that these drugs are effective across all domains of this complex disease.

Tumor necrosis factor (TNF) inhibitors in particular have proven beneficial in the treatment of the peripheral arthritis, skin and nail disease, axial disease, dactylitis, and enthesitis associated with psoriatic arthritis (PsA).

Traditional disease-modifying antirheumatic drugs such as methotrexate, in contrast, may be useful for the arthritis and skin and nail disease, but are less effective for the other disease manifestations, according to Dr. Philip Mease, of the University of Washington, chief of rheumatology research, Swedish Medical Center, and head, Seattle Rheumatology Associates.

This difference in therapeutic efficacy may relate to important differences in pathophysiology between PsA and rheumatoid arthritis (RA).

For example, the synovitis in PsA is associated with less sublining infiltrate and with greater vascularity than in RA. There is also an increased expression of toll-like receptors 2 and 4 and an increased number of polymorphonuclear leukocytes, suggesting a greater role for the innate immune system and possibly microbial antigen stimulation, Dr. Mease said at a rheumatology meeting sponsored by New York University.

In PsA there also is a role for unique lineages of monocytes effector cells that differentiate into macrophages, osteoclasts, Langerhans cells, and dendritic cells via specific microenvironmental signals, he said.

Trials of anti-TNF drugs in PsA have permitted, but not required, both background methotrexate, nonsteroidal anti-inflammatories, and low-dose prednisone, and patients with oligoarticular disease have been included.

For infliximab, newly published 98-week data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) demonstrate a similar degree of sustained effectiveness.

In the open-label extension phase of the current trial, 62% of the 78 patients continuing on the drug at week 98 had achieved an American College of Rheumatology 20 (ACR20) response, while 45% and 35% had ACR50 and ACR70 responses, respectively.

Among those whose baseline PASI score was 2.5 or greater, 64% achieved a 75% improvement (J. Rheumatol., First Release March 15, 2008).

Similar results also have been seen with adalimumab, with 70% of patients reaching a PASI 75 response and improvements in disability being sustained out to week 48 (Arthritis Rheum. 2007;56:476–88).

For etanercept, 2-year data demonstrated sustained effectiveness in ACR scores over time and inhibition of progression of radiologic damage. Approximately 40% of patients achieved Psoriasis Area Severity Index (PASI) 75 responses (J. Rheumatol. 2006;33:712–21).

But unanswered questions remain regarding the use of anti-TNF drugs for PsA, such as whether additional benefits result from adding methotrexate, Dr. Mease said.

Because the trials thus far have been inconsistent as to whether background methotrexate was used, what is needed to answer this question is a trial that enrolls methotrexate-naive patients and randomizes them to methotrexate monotherapy, anti-TNF monotherapy, or the combination, he said.

“We also don't know what the impact of these drugs will be on PsA comorbidities,” he said.

RA registries are showing benefits in terms of cardiovascular outcomes, and this may also be the case in PsA. The answers will only come from sources such as the Consortium of Rheumatology Researchers of North America (CORRONA) database, which is collecting long-term data not only on outcomes in RA but also on PsA, osteoarthritis, and osteoporosis.

It also remains to be seen if other comorbidities associated with PsA will benefit from anti-TNF therapy, including infection, lymphoma, and depression.

“A further question is what we should do about patients who are inadequately responding to these anti-TNFs,” he said. A variety of other therapies are being assessed, including other anti-TNFs such as golimumab, intra-articular anti-TNF agents, other cytokine targets such as interleukin-12/interleukin-23, B-cell ablation with rituximab, and small molecules such as the JAK3 inhibitor.

Another new area of exploration in the spondylarthropathies is the use of anti-TNF drugs in preradiographic ankylosing spondylitis (AS), Dr. Mease noted.

In an open-label extension study of 22 patients with early axial spondylarthritis but without radiographic sacroiliitis, 46% of patients receiving adalimumab had a sustained 40% improvement in the Assessments in Ankylosing Spondylitis 40 (ASAS40) criteria (Ann. Rheum. Dis. 2007;66[suppl II]:64–5).

The impact of anti-TNF drugs on PsA comorbidities is unknown, but good CV outcomes are seen in RA registries. DR. MEASE

NEW YORK — Increasing experience with the biologic agents in psoriatic arthritis is showing that these drugs are effective across all domains of this complex disease.

Tumor necrosis factor (TNF) inhibitors in particular have proven beneficial in the treatment of the peripheral arthritis, skin and nail disease, axial disease, dactylitis, and enthesitis associated with psoriatic arthritis (PsA).

Traditional disease-modifying antirheumatic drugs such as methotrexate, in contrast, may be useful for the arthritis and skin and nail disease, but are less effective for the other disease manifestations, according to Dr. Philip Mease, of the University of Washington, chief of rheumatology research, Swedish Medical Center, and head, Seattle Rheumatology Associates.

This difference in therapeutic efficacy may relate to important differences in pathophysiology between PsA and rheumatoid arthritis (RA).

For example, the synovitis in PsA is associated with less sublining infiltrate and with greater vascularity than in RA. There is also an increased expression of toll-like receptors 2 and 4 and an increased number of polymorphonuclear leukocytes, suggesting a greater role for the innate immune system and possibly microbial antigen stimulation, Dr. Mease said at a rheumatology meeting sponsored by New York University.

In PsA there also is a role for unique lineages of monocytes effector cells that differentiate into macrophages, osteoclasts, Langerhans cells, and dendritic cells via specific microenvironmental signals, he said.

Trials of anti-TNF drugs in PsA have permitted, but not required, both background methotrexate, nonsteroidal anti-inflammatories, and low-dose prednisone, and patients with oligoarticular disease have been included.

For infliximab, newly published 98-week data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT) demonstrate a similar degree of sustained effectiveness.

In the open-label extension phase of the current trial, 62% of the 78 patients continuing on the drug at week 98 had achieved an American College of Rheumatology 20 (ACR20) response, while 45% and 35% had ACR50 and ACR70 responses, respectively.

Among those whose baseline PASI score was 2.5 or greater, 64% achieved a 75% improvement (J. Rheumatol., First Release March 15, 2008).

Similar results also have been seen with adalimumab, with 70% of patients reaching a PASI 75 response and improvements in disability being sustained out to week 48 (Arthritis Rheum. 2007;56:476–88).

For etanercept, 2-year data demonstrated sustained effectiveness in ACR scores over time and inhibition of progression of radiologic damage. Approximately 40% of patients achieved Psoriasis Area Severity Index (PASI) 75 responses (J. Rheumatol. 2006;33:712–21).

But unanswered questions remain regarding the use of anti-TNF drugs for PsA, such as whether additional benefits result from adding methotrexate, Dr. Mease said.

Because the trials thus far have been inconsistent as to whether background methotrexate was used, what is needed to answer this question is a trial that enrolls methotrexate-naive patients and randomizes them to methotrexate monotherapy, anti-TNF monotherapy, or the combination, he said.

“We also don't know what the impact of these drugs will be on PsA comorbidities,” he said.

RA registries are showing benefits in terms of cardiovascular outcomes, and this may also be the case in PsA. The answers will only come from sources such as the Consortium of Rheumatology Researchers of North America (CORRONA) database, which is collecting long-term data not only on outcomes in RA but also on PsA, osteoarthritis, and osteoporosis.

It also remains to be seen if other comorbidities associated with PsA will benefit from anti-TNF therapy, including infection, lymphoma, and depression.

“A further question is what we should do about patients who are inadequately responding to these anti-TNFs,” he said. A variety of other therapies are being assessed, including other anti-TNFs such as golimumab, intra-articular anti-TNF agents, other cytokine targets such as interleukin-12/interleukin-23, B-cell ablation with rituximab, and small molecules such as the JAK3 inhibitor.

Another new area of exploration in the spondylarthropathies is the use of anti-TNF drugs in preradiographic ankylosing spondylitis (AS), Dr. Mease noted.

In an open-label extension study of 22 patients with early axial spondylarthritis but without radiographic sacroiliitis, 46% of patients receiving adalimumab had a sustained 40% improvement in the Assessments in Ankylosing Spondylitis 40 (ASAS40) criteria (Ann. Rheum. Dis. 2007;66[suppl II]:64–5).

The impact of anti-TNF drugs on PsA comorbidities is unknown, but good CV outcomes are seen in RA registries. DR. MEASE

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

MONT TREMBLANT, QUE. — Abatacept and infliximab exhibit different characteristics in their propensity to elicit autoantibody seroconversion and in their immunogenicity profiles in patients with rheumatoid arthritis, according to findings from a new analysis of data from a multicenter phase III trial.

As with all immunomodulatory agents, the development of autoimmune disorders and the formation of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) is of concern in patients who are being treated with abatacept or infliximab, said Dr. Jacques Brown of le Centre Hospitalier Universitaire de Quebec.

Recombinant biologic agents also have the potential to elicit immunogenicity, and the associated antibodies might mediate drug clearance or prevent its binding to its pharmacologic target.

Moreover, antibodies against anti-tumor necrosis factor therapy have been associated with decreased efficacy and an increased risk of infusion reactions, according to Dr. Brown.

The current analysis investigated 431 patients with rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive either abatacept, 10 mg/kg, on days 1, 15, and 29, and every 4 weeks thereafter; or infliximab, 3 mg/kg on days 1, 15, 43, and 85, and every 56 days thereafter for 6 months; or placebo.

Patients' mean age was 49 years and mean disease duration was 8 years. All had active disease, with a mean Disease Activity Score 28 of 6.8, tender joint counts above 30 and swollen joint counts above 20, and poor physical function on the Health Assessment Questionnaire Disability Index.

At baseline, 87% of the patients who were receiving abatacept were rheumatoid-factor positive, as were 85% of those patients who were randomized to the infliximab group.

At 6 months, 2% of the abatacept group, 5% of the placebo group, and 32% of the infliximab group had become ANA positive, whereas 1%, 4%, and 39% of these groups had seroconverted to positivity for anti-dsDNA antibodies, Dr. Brown reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

By 1 year, 7% of patients in the abatacept group and 48% of the infliximab group had become ANA positive, whereas 2% of the abatacept group and 48% of the infliximab group had become anti-dsDNA positive.

The patients initially randomized to placebo were switched to abatacept at 6 months and were not included in this analysis.

During the 6-month double-blind phase of the trial, none of the abatacept-treated patients developed antibodies against the drug, whereas 62% of the infliximab-treated patients had developed anti-infliximab antibodies.

During the double-blind phase, one patient in each group developed an autoimmune disorder.

One patient on abatacept developed vasculitis, one patient receiving placebo developed leukocytoclastic vasculitis, and one patient on infliximab developed sicca syndrome.

By 1 year, one additional patient who originally was randomized to placebo and later was switched to abatacept developed vasculitis.

Infusion reactions, which most commonly consisted of hypotension, headache, and nausea, were seen in 5%, 10%, and 18% of patients in the abatacept, placebo, and infliximab groups, respectively.

By 1 year these reactions were seen in 7% and 25% of the abatacept and infliximab groups.

The profiles of ANA and anti-dsDNA antibodies were markedly different in the two active treatment groups, although this difference did not translate into an increase in autoimmunity, with very few patients developing autoimmune disorders.

Furthermore, because vasculitis and sicca syndrome are associated with rheumatoid arthritis, it is difficult to determine whether the association is with the disease or with the use of biologic agents, Dr. Brown wrote.

The clinical impact of these differences remains to be elucidated, he added.

The study was sponsored by Bristol-Myers Squibb Co.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

MONT TREMBLANT, QUE. — Patients with rheumatoid arthritis treated with abatacept for 2 years reported improvements in fatigue, pain severity, and sleep, three key concerns for these patients, Dr. Anthony S. Russell reported at the annual meeting of the Canadian Rheumatology Association.

Several years ago at a meeting of the international network known as OMERACT, which formerly stood for Outcome Measures in Rheumatoid Arthritis Clinical Trials but now simply refers to Outcome Measures in Rheumatology, patients with rheumatoid arthritis (RA) were asked about their treatment priorities.

“Patients wanted to know if treatment will make them feel better, if it will get rid of pain and fatigue, and help them sleep,” said Dr. Russell of the University of Alberta, Edmonton.

Accordingly, these concerns were addressed during the open-label phase of two randomized trials of abatacept, a costimulatory modulator that inhibits full T-cell activation and reduces the proliferation of subsequent downstream inflammatory mediators such as interleukin-6 and C-reactive protein (J. Rheumatol. 2006;33:2162-6).

The two trials were the 12-month AIM (Abatacept in Inadequate Responders to Methotrexate) study and the 6-month ATTAIN (Abatacept Trial in Treatment of Anti-Tumor Necrosis Factor Inadequate Responders) study, both of which were sponsored by Bristol-Myers Squibb Co., makers of Orencia (abatacept). Patients who completed the double-blind phase of these trials and achieved at least an ACR 20 response were eligible to enroll in the 2-year open-label extension phase.

The treatment regimen in the blinded phase of the trials involved administration of a fixed dose of abatacept (approximately 10 mg/kg) on days 1, 15, 29, and every 4 weeks thereafter. Every 4-week administration was continued throughout the open-label phase.

To assess fatigue severity, patients were asked, “How much fatigue have you had because of your RA over the past week?” and rated this on a 100-mm visual analog scale (VAS).

Pain severity also was measured on a 100-mm VAS, and sleep quality was assessed using the Medical Outcomes Study Sleep Scale and a sleep problems index.

A total of 378 patients entered the long-term phase of AIM, as did 218 in ATTAIN.

Mean age of patients in AIM was 51 years, 77% were women, and the mean duration of RA was 8 years.

In ATTAIN, patients' mean age was 53 years, 77% were women, and the mean duration of RA was 12 years.

In both trials, the mean number of tender joints was 31 and the mean number of swollen joints was 22. The mean C-reactive protein level was 3.2 mg/dL in AIM and 4.6 mg/dL in ATTAIN.

At baseline in AIM, 44% of patients reported VAS scores higher than 70 for both fatigue and pain, and 9% had this degree of severity for sleep problems. After 2 years of abatacept treatment, these percentages were reduced to 10%, 4%, and 2%, respectively, Dr. Russell reported in a poster session.

Also after 2 years of treatment VAS scores below 30 were reported by 53%, 64%, and 49% for fatigue, pain, and sleep problems, respectively.

“Pain and fatigue improved markedly,” he said.

Similar results were seen in ATTAIN, despite the fact that patients in that trial were somewhat sicker.

All had failed at least one tumor necrosis factor inhibitor, and many had failed two, Dr. Russell said.

At baseline in ATTAIN, VAS scores of 70 and higher were reported by 68% of study participants for fatigue, by 58% of participants for pain, and by 13% for sleep problems.

After 2 years, these percentages had decreased to 24%, 9%, and 4%, respectively, while scores below 30 were reported by 33%, 51%, and 39%.

“By providing around-the-clock improvements in quality of life—pain and fatigue during the daytime and sleep quality during the night—abatacept has the potential to provide meaningful patient-centered benefits in moderate to severe RA,” Dr. Russell wrote.

“We can say to patients, yes, we listened to your concerns,” he said during the poster presentation.

Patients with rheumatoid arthritis are at an increased risk of contracting infections that are severe enough to require hospitalization, compared with people without rheumatoid arthritis, and the use of oral corticosteroids exacerbates that risk, according to results from a recent study.

The results further emphasize the notion that patients should be adequately informed about the heightened risk of infection with glucocorticoids.

“Patients should be routinely vaccinated against influenza, [and also] receive a pneumococcal vaccine,” Dr. Mark Hochberg, coinvestigator and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore, said in an interview.

The researchers conducted a retrospective cohort study based on records from 61 health plans across the United States from Jan. 1, 1999, through July 31, 2006.

A total of 24,530 patients were included in the RA cohort (inclusion criteria for this group were age over 18 years with at least two physician visits more than 2 months apart for RA with an ICD-9-CM diagnosis code of 714), and a random sample of 500,000 people were included in the non-RA cohort (age over 18 years and no RA diagnosis code at follow-up).

Patients in the RA cohort were more likely to be female than in the non-RA cohort, and a greater portion of RA patients were aged 45-64 years than in the non-RA cohort (66% vs. 39%, respectively).

During the study period, “there were 1,993 cases of a first hospitalized infection in the RA cohort, while 11,977 cases were observed in the non-RA cohort,” wrote the authors.

This translated to 3,864 cases per 100,000 person-years in the RA cohort and 1,250 cases per 100,000 years in the non-RA cohort and—adjusted for age, sex, and calendar year—gave a hazard ratio of 2.31 for hospitalized infection (95% confidence interval, 2.20-2.43).

Adjusted again for comorbid conditions and for prescription medication use, the hazard ratio was still 2.03 (95% CI, 1.93-2.13).

The most common infection in both groups was pneumonia, followed by urinary tract infections and after that, skin infections (J. Rheumatol. 2008;35:387-93).

The study investigators then performed a nested case-control analysis using all 1,993 hospitalized infection cases in the RA cohort and 9,965 RA controls, to ascertain whether the use of RA drugs further increased the patients' risk of infection.

Adjusted for age, sex, other current RA medication use, and a number of other chronic conditions, as well as the number of hospitalizations between the cohort entry and the index date, the researchers found a slightly increased risk when patients were taking biological disease modifying antirheumatic drugs (DMARDs).

These drugs included infliximab, etanercept, adalimumab, and anakinra (rate ratio 1.21, 95% CI 1.02-1.43).

However, the greatest risk for infection was conferred by current use of oral corticosteroids, and that risk was dose related.

Use of the drugs at less than or equal to 5 mg/day (in prednisone equivalents) was associated with a 1.32 relative risk of infection; use of between 6 mg/day and 10 mg/day, with a 1.94 relative risk.

And use of greater than 10 mg/day had a relative risk for infection of 2.98 (95% CI, 2.41-3.69).

In conclusion, the researchers wrote that methotrexate and hydroxychloroquine were actually associated with decreased risk of hospitalized infection, “whereas for sulfasalazine, leflunomide, and other traditional DMARDs, there was no association.”

The authors wrote that their study was limited by the possibility of misclassification of patients into the RA cohort and also by their inability to assess disease severity and patients' history of prior events.

The study received support from Bristol Myers Squibb Co.

Patients with rheumatoid arthritis are at an increased risk of contracting infections that are severe enough to require hospitalization, compared with people without rheumatoid arthritis, and the use of oral corticosteroids exacerbates that risk, according to results from a recent study.

The results further emphasize the notion that patients should be adequately informed about the heightened risk of infection with glucocorticoids.

“Patients should be routinely vaccinated against influenza, [and also] receive a pneumococcal vaccine,” Dr. Mark Hochberg, coinvestigator and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore, said in an interview.

The researchers conducted a retrospective cohort study based on records from 61 health plans across the United States from Jan. 1, 1999, through July 31, 2006.

A total of 24,530 patients were included in the RA cohort (inclusion criteria for this group were age over 18 years with at least two physician visits more than 2 months apart for RA with an ICD-9-CM diagnosis code of 714), and a random sample of 500,000 people were included in the non-RA cohort (age over 18 years and no RA diagnosis code at follow-up).

Patients in the RA cohort were more likely to be female than in the non-RA cohort, and a greater portion of RA patients were aged 45-64 years than in the non-RA cohort (66% vs. 39%, respectively).

During the study period, “there were 1,993 cases of a first hospitalized infection in the RA cohort, while 11,977 cases were observed in the non-RA cohort,” wrote the authors.

This translated to 3,864 cases per 100,000 person-years in the RA cohort and 1,250 cases per 100,000 years in the non-RA cohort and—adjusted for age, sex, and calendar year—gave a hazard ratio of 2.31 for hospitalized infection (95% confidence interval, 2.20-2.43).

Adjusted again for comorbid conditions and for prescription medication use, the hazard ratio was still 2.03 (95% CI, 1.93-2.13).

The most common infection in both groups was pneumonia, followed by urinary tract infections and after that, skin infections (J. Rheumatol. 2008;35:387-93).

The study investigators then performed a nested case-control analysis using all 1,993 hospitalized infection cases in the RA cohort and 9,965 RA controls, to ascertain whether the use of RA drugs further increased the patients' risk of infection.

Adjusted for age, sex, other current RA medication use, and a number of other chronic conditions, as well as the number of hospitalizations between the cohort entry and the index date, the researchers found a slightly increased risk when patients were taking biological disease modifying antirheumatic drugs (DMARDs).

These drugs included infliximab, etanercept, adalimumab, and anakinra (rate ratio 1.21, 95% CI 1.02-1.43).

However, the greatest risk for infection was conferred by current use of oral corticosteroids, and that risk was dose related.

Use of the drugs at less than or equal to 5 mg/day (in prednisone equivalents) was associated with a 1.32 relative risk of infection; use of between 6 mg/day and 10 mg/day, with a 1.94 relative risk.

And use of greater than 10 mg/day had a relative risk for infection of 2.98 (95% CI, 2.41-3.69).

In conclusion, the researchers wrote that methotrexate and hydroxychloroquine were actually associated with decreased risk of hospitalized infection, “whereas for sulfasalazine, leflunomide, and other traditional DMARDs, there was no association.”

The authors wrote that their study was limited by the possibility of misclassification of patients into the RA cohort and also by their inability to assess disease severity and patients' history of prior events.

The study received support from Bristol Myers Squibb Co.

Patients with rheumatoid arthritis are at an increased risk of contracting infections that are severe enough to require hospitalization, compared with people without rheumatoid arthritis, and the use of oral corticosteroids exacerbates that risk, according to results from a recent study.

The results further emphasize the notion that patients should be adequately informed about the heightened risk of infection with glucocorticoids.

“Patients should be routinely vaccinated against influenza, [and also] receive a pneumococcal vaccine,” Dr. Mark Hochberg, coinvestigator and head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore, said in an interview.

The researchers conducted a retrospective cohort study based on records from 61 health plans across the United States from Jan. 1, 1999, through July 31, 2006.

A total of 24,530 patients were included in the RA cohort (inclusion criteria for this group were age over 18 years with at least two physician visits more than 2 months apart for RA with an ICD-9-CM diagnosis code of 714), and a random sample of 500,000 people were included in the non-RA cohort (age over 18 years and no RA diagnosis code at follow-up).

Patients in the RA cohort were more likely to be female than in the non-RA cohort, and a greater portion of RA patients were aged 45-64 years than in the non-RA cohort (66% vs. 39%, respectively).

During the study period, “there were 1,993 cases of a first hospitalized infection in the RA cohort, while 11,977 cases were observed in the non-RA cohort,” wrote the authors.

This translated to 3,864 cases per 100,000 person-years in the RA cohort and 1,250 cases per 100,000 years in the non-RA cohort and—adjusted for age, sex, and calendar year—gave a hazard ratio of 2.31 for hospitalized infection (95% confidence interval, 2.20-2.43).

Adjusted again for comorbid conditions and for prescription medication use, the hazard ratio was still 2.03 (95% CI, 1.93-2.13).

The most common infection in both groups was pneumonia, followed by urinary tract infections and after that, skin infections (J. Rheumatol. 2008;35:387-93).

The study investigators then performed a nested case-control analysis using all 1,993 hospitalized infection cases in the RA cohort and 9,965 RA controls, to ascertain whether the use of RA drugs further increased the patients' risk of infection.

Adjusted for age, sex, other current RA medication use, and a number of other chronic conditions, as well as the number of hospitalizations between the cohort entry and the index date, the researchers found a slightly increased risk when patients were taking biological disease modifying antirheumatic drugs (DMARDs).

These drugs included infliximab, etanercept, adalimumab, and anakinra (rate ratio 1.21, 95% CI 1.02-1.43).

However, the greatest risk for infection was conferred by current use of oral corticosteroids, and that risk was dose related.

Use of the drugs at less than or equal to 5 mg/day (in prednisone equivalents) was associated with a 1.32 relative risk of infection; use of between 6 mg/day and 10 mg/day, with a 1.94 relative risk.

And use of greater than 10 mg/day had a relative risk for infection of 2.98 (95% CI, 2.41-3.69).

In conclusion, the researchers wrote that methotrexate and hydroxychloroquine were actually associated with decreased risk of hospitalized infection, “whereas for sulfasalazine, leflunomide, and other traditional DMARDs, there was no association.”

The authors wrote that their study was limited by the possibility of misclassification of patients into the RA cohort and also by their inability to assess disease severity and patients' history of prior events.

The study received support from Bristol Myers Squibb Co.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

MONT TREMBLANT, QUE. — Low-dose infliximab effectively reduced the signs and symptoms of active ankylosing spondylitis over 12 weeks in a double-blind, placebo-controlled trial, and response was maintained in a small group through 50 weeks, according to data from a randomized controlled trial.

In ankylosing spondylitis (AS), infliximab is generally given in doses of 5 mg/kg at weeks 0, 2, 6, and then every 8 weeks. If the drug could be given in 3 mg/kg, as is the case in rheumatoid arthritis, patients and the health care system stand to save a substantial amount of money, Dr. Robert D. Inman reported at the annual meeting of the Canadian Rheumatology Association.

In the CANDLE (Canadian Evaluation of Low-Dose Infliximab in Ankylosing Spondylitis) trial, 76 patients aged 18 years and older were randomized to receive a 3-mg/kg dose of infliximab or placebo intravenously at weeks 0, 2, and 6. The primary end point was the proportion of patients achieving an ASAS (Assessment in Ankylosing Spondylitis Working Group) 20 response at week 12.

About 80% of patients were male. Mean time since the first symptoms appeared was 19 years, and mean time since diagnosis was 11 years. In all, 73% were HLA B27 positive, approximately 10% had a history of inflammatory bowel disease, 34% had a history of uveitis, and 7% had a history of psoriasis.

At week 12, the percentage of patients achieving an ASAS 20 score was 54% in patients receiving infliximab versus 31% in patients receiving placebo.

Additionally, 41% and 21% of infliximab patients achieved ASAS 50 and ASAS 70 responses, respectively, compared with 6% and none of the placebo patients, according to poster presentation results presented by Dr. Inman, professor of medicine and immunology at the University of Toronto.

At week 12, the blind was broken and the infliximab group continued to receive the active treatment, while patients originally in the placebo group began infliximab therapy (3 mg/kg) at weeks 16, 18, 22, and every 8 weeks until week 46.

By week 50, 83% of patients in the original infliximab group and 80% of those who had been randomized to placebo but subsequently switched to the active drug had achieved an ASAS 20 response.

Additionally, 64% and 28% of the original infliximab group had achieved ASAS 50 and 70 responses, respectively, as had 69% and 40% of the original placebo group.

At week 12, patients in the infliximab group reported greater improvement in various domains of the Medical Outcomes Study SF-36 (short form-36), including body pain, vitality, social functioning, and mental health, and significant improvements in all eight domains were reported at weeks 22 and 50.

Most of the adverse events reported in the study were classified as unlikely to be related to the study medication. Only one patient discontinued the study because of an adverse event, Dr. Inman noted.

During the unblinded phase of the study, patients with an inadequate clinical response were permitted to have an increase in dose to 5 mg/kg. At week 22, 38% of patients previously in the placebo group required dose titration, as did 62% of those in the infliximab group.

By week 38, 67% of patients previously in the placebo group and 84% of those in the infliximab group required an increase in their infliximab dose, according to Dr. Inman, who dislcosed that he has served as consultant to Schering-Plough Corp., the study sponsor.

Although most patients did need the higher dose over time, a subset of patients will respond to induction and maintain response at 50 weeks with low-dose infliximab, Dr. Inman wrote.

A subanalysis in CANDLE included 32 patients who underwent spinal MRI at baseline and 12 weeks to evaluate the effects of low-dose infliximab on spinal inflammation as measured by the SPARCC (Spondyloarthritis Research Consortium of Canada) MRI index.

At baseline, the mean SPARCC score was 18.03 in the placebo group and 17.63 in the infliximab group. Three patients had no spinal inflammation evidence at baseline.

At week 12, the mean SPARCC score remained at 18.03 in the placebo group but fell to a mean of 6.22 in the infliximab group, which was a statistically significant difference.

FORT LAUDERDALE, FLA. – Whites with osteoarthritis are twice as likely as are African Americans or Hispanics to have joint replacement surgery, and differences in access to care and socioeconomic status do not explain the disparity, according to a presentation at the World Congress on Osteoarthritis.

Overall, Hispanics are less familiar with the surgery. An educational intervention targeted toward ethnic patients could reduce this disparity, Dr. Maria Suarez-Almazor said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Researchers explored the “striking disparity” in the number of total joint replacement procedures between white and non-white patients in focus groups and a survey of nearly 200 people with knee osteoarthritis.

Willingness to undergo surgery depended upon a need to feel ready for the procedure and a belief that no other options remain, according to focus groups of people with knee osteoarthritis. Inner beliefs, familiarity with the surgery, trust in their physicians, and advice from others who had the procedure were also considered important. There were two focus groups of whites, two groups of African Americans, and two groups of Hispanics.

To assess cultural differences more quantitatively, Dr. Suarez-Almazor and her associates surveyed 198 patients with knee osteoarthritis via telephone or in person.

Findings were adjusted for age, education, and other differences. “Access to care and socioeconomic status alone cannot explain the variation,” Dr. Suarez-Almazor said.

White respondents had considered total knee replacement on their own the most often (42%), compared with 30% of African Americans and 25% of Hispanics, said Dr. Suarez-Almazor, professor in the department of general internal medicine, ambulatory treatment, and emergency care at the University of Texas MD Anderson Cancer Center, Houston.

A total of 100% of whites reported familiarity with total knee replacement surgery compared with 91% of African Americans and 80% of Hispanics. In addition, 80% of whites versus 70% of African Americans and 58% of Hispanics said they had a relative or friend who had the surgery.

Overall, Hispanics and African Americans thought surgery would be less beneficial than did whites. In addition, Hispanics reported they were less likely to undergo the procedure than, compared with whites, even if their osteoarthritis worsened and a doctor recommended the surgery.

FORT LAUDERDALE, FLA. – Whites with osteoarthritis are twice as likely as are African Americans or Hispanics to have joint replacement surgery, and differences in access to care and socioeconomic status do not explain the disparity, according to a presentation at the World Congress on Osteoarthritis.

Overall, Hispanics are less familiar with the surgery. An educational intervention targeted toward ethnic patients could reduce this disparity, Dr. Maria Suarez-Almazor said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Researchers explored the “striking disparity” in the number of total joint replacement procedures between white and non-white patients in focus groups and a survey of nearly 200 people with knee osteoarthritis.

Willingness to undergo surgery depended upon a need to feel ready for the procedure and a belief that no other options remain, according to focus groups of people with knee osteoarthritis. Inner beliefs, familiarity with the surgery, trust in their physicians, and advice from others who had the procedure were also considered important. There were two focus groups of whites, two groups of African Americans, and two groups of Hispanics.

To assess cultural differences more quantitatively, Dr. Suarez-Almazor and her associates surveyed 198 patients with knee osteoarthritis via telephone or in person.

Findings were adjusted for age, education, and other differences. “Access to care and socioeconomic status alone cannot explain the variation,” Dr. Suarez-Almazor said.

White respondents had considered total knee replacement on their own the most often (42%), compared with 30% of African Americans and 25% of Hispanics, said Dr. Suarez-Almazor, professor in the department of general internal medicine, ambulatory treatment, and emergency care at the University of Texas MD Anderson Cancer Center, Houston.

A total of 100% of whites reported familiarity with total knee replacement surgery compared with 91% of African Americans and 80% of Hispanics. In addition, 80% of whites versus 70% of African Americans and 58% of Hispanics said they had a relative or friend who had the surgery.

Overall, Hispanics and African Americans thought surgery would be less beneficial than did whites. In addition, Hispanics reported they were less likely to undergo the procedure than, compared with whites, even if their osteoarthritis worsened and a doctor recommended the surgery.

FORT LAUDERDALE, FLA. – Whites with osteoarthritis are twice as likely as are African Americans or Hispanics to have joint replacement surgery, and differences in access to care and socioeconomic status do not explain the disparity, according to a presentation at the World Congress on Osteoarthritis.

Overall, Hispanics are less familiar with the surgery. An educational intervention targeted toward ethnic patients could reduce this disparity, Dr. Maria Suarez-Almazor said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Researchers explored the “striking disparity” in the number of total joint replacement procedures between white and non-white patients in focus groups and a survey of nearly 200 people with knee osteoarthritis.

Willingness to undergo surgery depended upon a need to feel ready for the procedure and a belief that no other options remain, according to focus groups of people with knee osteoarthritis. Inner beliefs, familiarity with the surgery, trust in their physicians, and advice from others who had the procedure were also considered important. There were two focus groups of whites, two groups of African Americans, and two groups of Hispanics.

To assess cultural differences more quantitatively, Dr. Suarez-Almazor and her associates surveyed 198 patients with knee osteoarthritis via telephone or in person.

Findings were adjusted for age, education, and other differences. “Access to care and socioeconomic status alone cannot explain the variation,” Dr. Suarez-Almazor said.

White respondents had considered total knee replacement on their own the most often (42%), compared with 30% of African Americans and 25% of Hispanics, said Dr. Suarez-Almazor, professor in the department of general internal medicine, ambulatory treatment, and emergency care at the University of Texas MD Anderson Cancer Center, Houston.

A total of 100% of whites reported familiarity with total knee replacement surgery compared with 91% of African Americans and 80% of Hispanics. In addition, 80% of whites versus 70% of African Americans and 58% of Hispanics said they had a relative or friend who had the surgery.

Overall, Hispanics and African Americans thought surgery would be less beneficial than did whites. In addition, Hispanics reported they were less likely to undergo the procedure than, compared with whites, even if their osteoarthritis worsened and a doctor recommended the surgery.

FORT LAUDERDALE, FLA. – Pain catastrophizing and pain-related fear are associated with increased disability and worse physical functioning among overweight patients with osteoarthritis, according to a study presented at the World Congress on Osteoarthritis.

“In the cognitive-behavioral area, what people are thinking about pain while they are having it can have a significant effect,” said Francis J. Keefe, Ph.D. “We need to be thinking about pain-related cognitions. These can increase the patient perception of pain.”

Researchers assessed pain among 106 patients with knee osteoarthritis. They also evaluated psychological disability, physical impairment, and walking velocity while controlling for pain levels. They measured walking velocity, stride length, and knee range of motion. Mean body mass index was 35 kg/m

Dr. Keefe and his associates sought to assess how pain catastrophizing and pain-related fear might affect psychological and physical functioning in this patient population. It already is well accepted that increased body weight can increase severity of knee osteoarthritis, he said.

People who catastrophize focus on their pain and magnify it. They can misinterpret pain as more threatening than it is and underestimate their ability to manage it. “Pain catastrophizing tends to increase the pain experience and disability. The reason people do this is it tends to pull other people into their situation,” said Dr. Keefe, who is with the medical psychology division, psychiatry and behavioral sciences department, Duke University, Durham, N.C.

Pain-related fear includes excessive fear of experiencing pain during movement, or kinesiophobia. This phenomenon “is especially important in the obese with osteoarthritis if they are afraid to move,” Dr. Keefe said at the meeting, which was sponsored by Osteoarthritis Research Society International.

“Clinicians need to be aware of the effects of pain catastrophizing,” Dr. Keefe said.

All participants completed the Coping Strategies Questionnaire to assess pain catastrophizing, the Tampa Scale for Kinesiophobia to measure pain-related fear, and the Arthritis Self-Efficacy Scale. Self-efficacy for pain management was associated with improved physical functioning in the study.

Catastrophizing and pain-related fear were associated with higher psychological distress and lower pain self-efficacy. Pain-related fear, but not catastrophizing, was associated with worse physical functioning.

“The degree of catastrophizing was among the greatest we've seen,” he said.

Addressing pain catastrophizing among overweight people with knee osteoarthritis might improve psychological functioning, Dr. Keefe said. An intervention aimed at improving pain-related fear could improve physical functioning as well. “Coping skills training or cognitive-behavioral therapy could improve these cognitions, but they are challenging to do.”

Dr. Keefe and his associates plan to launch a new study that will randomize obese patients with osteoarthritis to behavioral weight management, pain coping skills training, both interventions, or control group. A posttreatment evaluation will be followed by reassessment at 6 and 12 months.

FORT LAUDERDALE, FLA. – Pain catastrophizing and pain-related fear are associated with increased disability and worse physical functioning among overweight patients with osteoarthritis, according to a study presented at the World Congress on Osteoarthritis.

“In the cognitive-behavioral area, what people are thinking about pain while they are having it can have a significant effect,” said Francis J. Keefe, Ph.D. “We need to be thinking about pain-related cognitions. These can increase the patient perception of pain.”

Researchers assessed pain among 106 patients with knee osteoarthritis. They also evaluated psychological disability, physical impairment, and walking velocity while controlling for pain levels. They measured walking velocity, stride length, and knee range of motion. Mean body mass index was 35 kg/m

Dr. Keefe and his associates sought to assess how pain catastrophizing and pain-related fear might affect psychological and physical functioning in this patient population. It already is well accepted that increased body weight can increase severity of knee osteoarthritis, he said.

People who catastrophize focus on their pain and magnify it. They can misinterpret pain as more threatening than it is and underestimate their ability to manage it. “Pain catastrophizing tends to increase the pain experience and disability. The reason people do this is it tends to pull other people into their situation,” said Dr. Keefe, who is with the medical psychology division, psychiatry and behavioral sciences department, Duke University, Durham, N.C.

Pain-related fear includes excessive fear of experiencing pain during movement, or kinesiophobia. This phenomenon “is especially important in the obese with osteoarthritis if they are afraid to move,” Dr. Keefe said at the meeting, which was sponsored by Osteoarthritis Research Society International.

“Clinicians need to be aware of the effects of pain catastrophizing,” Dr. Keefe said.

All participants completed the Coping Strategies Questionnaire to assess pain catastrophizing, the Tampa Scale for Kinesiophobia to measure pain-related fear, and the Arthritis Self-Efficacy Scale. Self-efficacy for pain management was associated with improved physical functioning in the study.

Catastrophizing and pain-related fear were associated with higher psychological distress and lower pain self-efficacy. Pain-related fear, but not catastrophizing, was associated with worse physical functioning.

“The degree of catastrophizing was among the greatest we've seen,” he said.

Addressing pain catastrophizing among overweight people with knee osteoarthritis might improve psychological functioning, Dr. Keefe said. An intervention aimed at improving pain-related fear could improve physical functioning as well. “Coping skills training or cognitive-behavioral therapy could improve these cognitions, but they are challenging to do.”

Dr. Keefe and his associates plan to launch a new study that will randomize obese patients with osteoarthritis to behavioral weight management, pain coping skills training, both interventions, or control group. A posttreatment evaluation will be followed by reassessment at 6 and 12 months.

FORT LAUDERDALE, FLA. – Pain catastrophizing and pain-related fear are associated with increased disability and worse physical functioning among overweight patients with osteoarthritis, according to a study presented at the World Congress on Osteoarthritis.

“In the cognitive-behavioral area, what people are thinking about pain while they are having it can have a significant effect,” said Francis J. Keefe, Ph.D. “We need to be thinking about pain-related cognitions. These can increase the patient perception of pain.”

Researchers assessed pain among 106 patients with knee osteoarthritis. They also evaluated psychological disability, physical impairment, and walking velocity while controlling for pain levels. They measured walking velocity, stride length, and knee range of motion. Mean body mass index was 35 kg/m

Dr. Keefe and his associates sought to assess how pain catastrophizing and pain-related fear might affect psychological and physical functioning in this patient population. It already is well accepted that increased body weight can increase severity of knee osteoarthritis, he said.

People who catastrophize focus on their pain and magnify it. They can misinterpret pain as more threatening than it is and underestimate their ability to manage it. “Pain catastrophizing tends to increase the pain experience and disability. The reason people do this is it tends to pull other people into their situation,” said Dr. Keefe, who is with the medical psychology division, psychiatry and behavioral sciences department, Duke University, Durham, N.C.

Pain-related fear includes excessive fear of experiencing pain during movement, or kinesiophobia. This phenomenon “is especially important in the obese with osteoarthritis if they are afraid to move,” Dr. Keefe said at the meeting, which was sponsored by Osteoarthritis Research Society International.

“Clinicians need to be aware of the effects of pain catastrophizing,” Dr. Keefe said.

All participants completed the Coping Strategies Questionnaire to assess pain catastrophizing, the Tampa Scale for Kinesiophobia to measure pain-related fear, and the Arthritis Self-Efficacy Scale. Self-efficacy for pain management was associated with improved physical functioning in the study.

Catastrophizing and pain-related fear were associated with higher psychological distress and lower pain self-efficacy. Pain-related fear, but not catastrophizing, was associated with worse physical functioning.

“The degree of catastrophizing was among the greatest we've seen,” he said.

Addressing pain catastrophizing among overweight people with knee osteoarthritis might improve psychological functioning, Dr. Keefe said. An intervention aimed at improving pain-related fear could improve physical functioning as well. “Coping skills training or cognitive-behavioral therapy could improve these cognitions, but they are challenging to do.”

Dr. Keefe and his associates plan to launch a new study that will randomize obese patients with osteoarthritis to behavioral weight management, pain coping skills training, both interventions, or control group. A posttreatment evaluation will be followed by reassessment at 6 and 12 months.

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

FORT LAUDERDALE, FLA. – The walk of a patient with osteoarthritis differs by which knee compartments are affected, according to researchers who linked radiographic findings with sophisticated motion analysis.

Knee osteoarthritis (OA) leads to alterations in gait that can further impair function for patients, Dr. William F. Harvey said at the World Congress on Osteoarthritis. To find out if there are gait alterations unique to the compartments of the knee that are affected by OA, Dr. Harvey and his associates assessed 448 patients in North Carolina enrolled in the Observational Arthritis Study in Seniors (OASIS).

Participants' mean age was 72 years and all were more than 65 years old; all reported knee pain. Just more than half, 51%, were women; 83% were white; and the mean body mass index was 30 kg/m

At baseline, researchers found that 166 patients had grade 0 Kellgren-Lawrence (KL), 51 patients had grade 1 KL, 47 patients had grade 2 KL, 126 patients had grade 3 KL, and 58 patients had grade 4 KL; in general, the higher the KL grade, the worse the meniscal pathology and chondral degradation, Dr. Harvey, a fellow in rheumatology at Boston University, said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Kinematic measures of gait were performed during self-paced walking in the sagittal plane only, with outcomes based on an average of three trials. Peak angular range of motion, mean angular velocity (of the hip, knee, and ankle joints), stride length, walking velocity, cadence, and stance and swing times were measured. Mean values were compared between groups. Results were adjusted for age, race, gender, body mass index, and walking velocity.

Patients with isolated tibio-femoral (159 participants), and both tibiofemoral and patellofemoral osteoarthritis (72 participants) had a significantly lower knee range of motion and mean angular velocity, compared with those with no osteoarthritis (206 participants), Dr. Harvey said. The mean knee range of motion angle was 54 degrees in the tibiofemoral group and 53 degrees in the combined group, compared with 57 degrees in the unaffected group. The mean value for the patellofemoral osteoarthritis group, 58 degrees, was not statistically significant because of the small number of patients in the category.

In addition, there was a statistically significant difference in mean angular velocity of the knee between the same groups. Those with tibiofemoral osteoarthritis and both compartments affected had a lower mean angular velocity, compared with those without osteoarthritis, Dr. Harvey said. Expressed as degrees per second, the values were 104 in the tibiofemoral group, 100 in the group with both compartments affected, and 117 in the comparison, disease-free, group without disease. Again, the 110 degrees per second finding in the patellofemoral group was not significant.

Stance time was another variable that was significantly different between groups. The patellofemoral group and doubly affected group spent more time in stance versus swing, compared with the tibiofemoral osteoarthritis group or the unaffected patients.

The study was funded by Wake Forest University and a grant from the National Institutes of Health.

ELSEVIER GLOBAL MEDICAL NEWS

RHEUMATOLOGY NEWS and “The Pink Sheet” are published by Elsevier.

Companies marketing unapproved drugs that contain injectable colchicine to treat gout have 30 days to stop manufacturing and 180 days to stop shipping the drug, which has caused 23 reported deaths, according to the U.S. Food and Drug Administration.

All injectable colchicine drugs on the market 180 days after the FDA's announcement on Feb. 6 must have the agency's approval. Refusal could result in regulatory action, including seizure, injunction, or other legal action, according to the FDA statement. The enforcement measure marks the seventh action taken by the agency against companies marketing and selling unapproved drugs since issuing its Compliance Policy Guide. Colchicine tablets will remain on the market for now.

Injectable colchicine has been approved for treatment of gout in the U.S. since the 1950s. It is rarely administered because its use results in harmful adverse events or death.

For more information on the FDA's action, please go to http://www.fda.gov/cder/drug/unapproved_drugs/colchicine_qa.htm

RHEUMATOLOGY NEWS and “The Pink Sheet” are published by Elsevier.

Companies marketing unapproved drugs that contain injectable colchicine to treat gout have 30 days to stop manufacturing and 180 days to stop shipping the drug, which has caused 23 reported deaths, according to the U.S. Food and Drug Administration.

All injectable colchicine drugs on the market 180 days after the FDA's announcement on Feb. 6 must have the agency's approval. Refusal could result in regulatory action, including seizure, injunction, or other legal action, according to the FDA statement. The enforcement measure marks the seventh action taken by the agency against companies marketing and selling unapproved drugs since issuing its Compliance Policy Guide. Colchicine tablets will remain on the market for now.

Injectable colchicine has been approved for treatment of gout in the U.S. since the 1950s. It is rarely administered because its use results in harmful adverse events or death.

For more information on the FDA's action, please go to http://www.fda.gov/cder/drug/unapproved_drugs/colchicine_qa.htm

RHEUMATOLOGY NEWS and “The Pink Sheet” are published by Elsevier.

Companies marketing unapproved drugs that contain injectable colchicine to treat gout have 30 days to stop manufacturing and 180 days to stop shipping the drug, which has caused 23 reported deaths, according to the U.S. Food and Drug Administration.

All injectable colchicine drugs on the market 180 days after the FDA's announcement on Feb. 6 must have the agency's approval. Refusal could result in regulatory action, including seizure, injunction, or other legal action, according to the FDA statement. The enforcement measure marks the seventh action taken by the agency against companies marketing and selling unapproved drugs since issuing its Compliance Policy Guide. Colchicine tablets will remain on the market for now.

Injectable colchicine has been approved for treatment of gout in the U.S. since the 1950s. It is rarely administered because its use results in harmful adverse events or death.

For more information on the FDA's action, please go to http://www.fda.gov/cder/drug/unapproved_drugs/colchicine_qa.htm