Rheumatoid Arthritis

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

Treatment with adalimumab significantly improved quality of life and functioning among patients with moderate to severe psoriatic arthritis at 24 weeks, reported Dr. Dafna D. Gladman.

Previous analyses from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest randomized controlled trial of a tumor necrosis factor (TNF)-α inhibitor in psoriatic arthritis, have demonstrated that treatment with this drug significantly improves joint and skin manifestations and reduces radiographic disease progression.

But because psoriatic arthritis primarily afflicts patients in the productive years, 30–55 years, restoring function and reducing work-related disability also could help ease the economic burden of this disease, according to Dr. Gladman of the University of Toronto Rheumatic Disease Unit.

Among the 313 patients in ADEPT, those receiving adalimumab had a mean decrease of 0.4 points from a baseline score of 1.0 on the disease-specific Health Assessment Questionnaire Disability Index, which has a range of 0 to 3, while those receiving placebo had a decrease of 0.1 points, Dr. Gladman and colleagues reported (Ann. Rheum. Dis. [Epub doi: 10.1136/ard.2006.057901

By week 12, 33.8% of patients in the active treatment group had complete resolution of functional loss, compared with 14.3% of those in the placebo group, with similar results being seen at week 24, according to the investigators. Statistically significant and clinically important improvements also were seen at week 24 in seven of the eight domains of the Short Form 36 Health Survey among the adalimumab-treated patients, whereas patients receiving placebo did not experience clinically important improvements in any domain.

The investigators acknowledged that a limitation of their study was its short duration, but noted that data from the long-term, open-label extension of ADEPT are being assessed.

Risedronate appears to be no better than placebo at improving symptoms and slowing structural changes associated with osteoarthritis, but the drug did significantly reduce markers of bone resorption and cartilage degradation, providing some measure of hope that the drug may still prove useful in treating this disorder.

“In the groups that were receiving placebo, there was worsening of their cartilage degradation marker [C-terminal crosslinking telopeptide of type II collagen, or CTX-II], whereas there was a dose-dependent reduction in all of the rise dronate treated patients. To date, CTX-II is the leading biomarker for osteoarthritis in terms of one that may be predictive of patients who are at risk for progression,” Dr. Clifton O. Bingham III, the study's lead author and a rheumatologist at Johns Hopkins University, Baltimore, said.

Whether these changes in biomarkers will translate into a later clinically relevant change in joint preservation is unknown. “The fact that we are able to now show that certain treatments can affect this biomarker is really a very important piece for us in order to move forward in the development of therapeutics,” said Dr. Bingham, who reported receiving consulting fees from Procter & Gamble Pharmaceuticals Inc., maker of risedronate (Actonel).

The study was conducted at 42 sites in North America and at 44 sites in the European Union (Arthritis Rheum. 2006;54:3494–507). Patients were randomized to receive placebo or oral risedronate in dosages of 5 mg/day, 15 mg/day, 35 mg/week (Europe only), or 50 mg/week (North America only).

Patients aged 40–80 years were screened for inclusion if they had signal knee pain resulting from osteoarthritis (OA) most days during at least 1 month in a 3-month period, and had one of the following: morning knee stiffness lasting more than 30 minutes, or knee crepitus according to the American College of Rheumatology criteria for knee OA.

Patients were excluded if they had known inflammatory arthritis; body mass index (kg/m

All patients underwent radiography of the knee to confirm OA. For inclusion, patients had to have at least one osteophyte and minimal joint space width of 2–4 mm, inclusive, in the medial tibiofemoral compartment, and a medial compartment that was narrower than the lateral. Radiographic assessment was performed at baseline, 1 year, and 2 years.

Nonnarcotic analgesics, NSAIDs, or COX-2 inhibitors were allowed and monitored during the study. Patients underwent a stepped reduction and washout period for these medications prior to study visits, including the baseline visit. Patients were provided with 500 mg acetaminophen (North America) or paracetamol (Europe) and 50 mg diclofenac to be used as needed from 5 to 3 days prior to a visit. All pain medications were stopped 2 days prior to a visit.

The two primary end points were the effect of risedronate on structure and symptoms compared with placebo after 2 years. Patient symptoms were measured by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and by Patient Global Assessment (PGA) scores. Structure was assessed by measuring joint-space narrowing in the medial tibiofemoral compartment.

Joint-space narrowing of the target knee was evaluated at the narrowest point in the medial tibiofemoral compartment at baseline and at 1 and 2 years follow-up. Radiographs were performed using a semiflexed view of the knee (fluoroscopically assisted). Radiographs were obtained at 13 regional radiographic facilities in Europe and 12 in the United States. All radiographs were sent to a quality control center in Amsterdam for review and then to the central analysis facility in London, where films were digitized and semiautomated computer measurements of minimal medial joint-space width were performed. The test-retest standard deviation—the difference between radiographs obtained 2 days apart—for this technique was approximately 0.2 mm.

Urine samples were also collected at baseline and at 6 months, 12 months, and 24 months. Samples were analyzed for N-terminal crosslinking telopeptide of type I collagen (NTX-I) to assess bone resorption and for CTX-II.

In the North American cohort, 301 participants were randomized to placebo, 306 to 5 mg/day risedronate, 302 to 15 mg/day, and 314 to 50 mg/week. In the European cohort, 312 participants were randomized to placebo, 322 to 5 mg/day risedronate, 307 to 15 mg/day, and 310 to 35 mg/week.

“In both the European and North American studies, no significant differences between treatment groups were noted in the mean change from baseline in total WOMAC score, scores for WOMAC components, or PGA scores,” the researchers said. Notably, those patients treated with placebo had a mean reduction of about 20% from baseline in total WOMAC scores.

“In all treatment groups, including the placebo, there was a clinically detectable improvement in pain that occurred at the 6-month point and was maintained over 2 years,” said Dr. Bingham. The results for the placebo patients highlight the importance of accounting for placebo benefit in osteoarthritis studies. Not only did placebo improvement occur, but it was maintained over time.

So either improvement is part of the natural course of the disease or there is a clinical benefit simply in entering a clinical trial. Regardless, this effect needs to be taken into consideration in designing future osteoarthritis trials, said Dr. Bingham, who is also with the division of allergy and immunology at Johns Hopkins University.

In terms of structure, 13% of participants had radiographic progression. There were no statistically significant differences in any treatment group in either cohort.

“When you looked at the people who were showing what was unequivocally progression … there was no drug effect that was demonstrated but interestingly that group of people was only a very small percentage of the entire study population,” said Dr. Bingham.

The radiographic findings also have implications for future trial design: If only a small number of people are going to show substantial worsening in terms of joint structure, then—in order to study an OA drug by looking at structure as an outcome—greater numbers of patients are needed to be able to demonstrate a potential treatment effect, he said.

In both cohorts, a dose-dependent decrease in the level of NTX-I was observed within 6 months for those on risedronate, and it continued through 24 months. The mean percent change from baseline to 24 months for all dosages of risedronate was statistically different from the placebo group. In the North American group, those on placebo had a mean increase in NTX-I of 7.3%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 50 mg/week had NTX-I level decreases of 21.6%, 39.2%, and 29.2%, respectively. In the European cohort, those on placebo had a mean increase in NTX-I of 3.0%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 35 mg/week had NTX-I level decreases of 29.0%, 41.7%, and 28.2%, respectively.

The results for CTX-II levels were similar, with those on placebo having increases over 24 months, whereas those on risedronate had early decreases. At 15 mg/day risedronate, reductions of 17.9% and 19.6% from baseline were seen in North American and European patients respectively. In comparison, the North American and European placebo groups had increases of CTX-II levels of 26.3% and 10.1%, respectively.

The biomarker results suggest—from a pathobiologic perspective—that an agent that acts on subchondral bone, interrupts the turnover of bone, and improves bone structure can consequently improve cartilage stability. This suggests a fundamental interaction between bone and cartilage. This could be important because treatments already are available that interrupt bone turnover.

These study results indicate that “potentially the bone is an important therapeutic target in patients with osteoarthritis,” said Dr. Bingham.

Risedronate appears to be no better than placebo at improving symptoms and slowing structural changes associated with osteoarthritis, but the drug did significantly reduce markers of bone resorption and cartilage degradation, providing some measure of hope that the drug may still prove useful in treating this disorder.

“In the groups that were receiving placebo, there was worsening of their cartilage degradation marker [C-terminal crosslinking telopeptide of type II collagen, or CTX-II], whereas there was a dose-dependent reduction in all of the rise dronate treated patients. To date, CTX-II is the leading biomarker for osteoarthritis in terms of one that may be predictive of patients who are at risk for progression,” Dr. Clifton O. Bingham III, the study's lead author and a rheumatologist at Johns Hopkins University, Baltimore, said.

Whether these changes in biomarkers will translate into a later clinically relevant change in joint preservation is unknown. “The fact that we are able to now show that certain treatments can affect this biomarker is really a very important piece for us in order to move forward in the development of therapeutics,” said Dr. Bingham, who reported receiving consulting fees from Procter & Gamble Pharmaceuticals Inc., maker of risedronate (Actonel).

The study was conducted at 42 sites in North America and at 44 sites in the European Union (Arthritis Rheum. 2006;54:3494–507). Patients were randomized to receive placebo or oral risedronate in dosages of 5 mg/day, 15 mg/day, 35 mg/week (Europe only), or 50 mg/week (North America only).

Patients aged 40–80 years were screened for inclusion if they had signal knee pain resulting from osteoarthritis (OA) most days during at least 1 month in a 3-month period, and had one of the following: morning knee stiffness lasting more than 30 minutes, or knee crepitus according to the American College of Rheumatology criteria for knee OA.

Patients were excluded if they had known inflammatory arthritis; body mass index (kg/m

All patients underwent radiography of the knee to confirm OA. For inclusion, patients had to have at least one osteophyte and minimal joint space width of 2–4 mm, inclusive, in the medial tibiofemoral compartment, and a medial compartment that was narrower than the lateral. Radiographic assessment was performed at baseline, 1 year, and 2 years.

Nonnarcotic analgesics, NSAIDs, or COX-2 inhibitors were allowed and monitored during the study. Patients underwent a stepped reduction and washout period for these medications prior to study visits, including the baseline visit. Patients were provided with 500 mg acetaminophen (North America) or paracetamol (Europe) and 50 mg diclofenac to be used as needed from 5 to 3 days prior to a visit. All pain medications were stopped 2 days prior to a visit.

The two primary end points were the effect of risedronate on structure and symptoms compared with placebo after 2 years. Patient symptoms were measured by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and by Patient Global Assessment (PGA) scores. Structure was assessed by measuring joint-space narrowing in the medial tibiofemoral compartment.

Joint-space narrowing of the target knee was evaluated at the narrowest point in the medial tibiofemoral compartment at baseline and at 1 and 2 years follow-up. Radiographs were performed using a semiflexed view of the knee (fluoroscopically assisted). Radiographs were obtained at 13 regional radiographic facilities in Europe and 12 in the United States. All radiographs were sent to a quality control center in Amsterdam for review and then to the central analysis facility in London, where films were digitized and semiautomated computer measurements of minimal medial joint-space width were performed. The test-retest standard deviation—the difference between radiographs obtained 2 days apart—for this technique was approximately 0.2 mm.

Urine samples were also collected at baseline and at 6 months, 12 months, and 24 months. Samples were analyzed for N-terminal crosslinking telopeptide of type I collagen (NTX-I) to assess bone resorption and for CTX-II.

In the North American cohort, 301 participants were randomized to placebo, 306 to 5 mg/day risedronate, 302 to 15 mg/day, and 314 to 50 mg/week. In the European cohort, 312 participants were randomized to placebo, 322 to 5 mg/day risedronate, 307 to 15 mg/day, and 310 to 35 mg/week.

“In both the European and North American studies, no significant differences between treatment groups were noted in the mean change from baseline in total WOMAC score, scores for WOMAC components, or PGA scores,” the researchers said. Notably, those patients treated with placebo had a mean reduction of about 20% from baseline in total WOMAC scores.

“In all treatment groups, including the placebo, there was a clinically detectable improvement in pain that occurred at the 6-month point and was maintained over 2 years,” said Dr. Bingham. The results for the placebo patients highlight the importance of accounting for placebo benefit in osteoarthritis studies. Not only did placebo improvement occur, but it was maintained over time.

So either improvement is part of the natural course of the disease or there is a clinical benefit simply in entering a clinical trial. Regardless, this effect needs to be taken into consideration in designing future osteoarthritis trials, said Dr. Bingham, who is also with the division of allergy and immunology at Johns Hopkins University.

In terms of structure, 13% of participants had radiographic progression. There were no statistically significant differences in any treatment group in either cohort.

“When you looked at the people who were showing what was unequivocally progression … there was no drug effect that was demonstrated but interestingly that group of people was only a very small percentage of the entire study population,” said Dr. Bingham.

The radiographic findings also have implications for future trial design: If only a small number of people are going to show substantial worsening in terms of joint structure, then—in order to study an OA drug by looking at structure as an outcome—greater numbers of patients are needed to be able to demonstrate a potential treatment effect, he said.

In both cohorts, a dose-dependent decrease in the level of NTX-I was observed within 6 months for those on risedronate, and it continued through 24 months. The mean percent change from baseline to 24 months for all dosages of risedronate was statistically different from the placebo group. In the North American group, those on placebo had a mean increase in NTX-I of 7.3%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 50 mg/week had NTX-I level decreases of 21.6%, 39.2%, and 29.2%, respectively. In the European cohort, those on placebo had a mean increase in NTX-I of 3.0%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 35 mg/week had NTX-I level decreases of 29.0%, 41.7%, and 28.2%, respectively.

The results for CTX-II levels were similar, with those on placebo having increases over 24 months, whereas those on risedronate had early decreases. At 15 mg/day risedronate, reductions of 17.9% and 19.6% from baseline were seen in North American and European patients respectively. In comparison, the North American and European placebo groups had increases of CTX-II levels of 26.3% and 10.1%, respectively.

The biomarker results suggest—from a pathobiologic perspective—that an agent that acts on subchondral bone, interrupts the turnover of bone, and improves bone structure can consequently improve cartilage stability. This suggests a fundamental interaction between bone and cartilage. This could be important because treatments already are available that interrupt bone turnover.

These study results indicate that “potentially the bone is an important therapeutic target in patients with osteoarthritis,” said Dr. Bingham.

Risedronate appears to be no better than placebo at improving symptoms and slowing structural changes associated with osteoarthritis, but the drug did significantly reduce markers of bone resorption and cartilage degradation, providing some measure of hope that the drug may still prove useful in treating this disorder.

“In the groups that were receiving placebo, there was worsening of their cartilage degradation marker [C-terminal crosslinking telopeptide of type II collagen, or CTX-II], whereas there was a dose-dependent reduction in all of the rise dronate treated patients. To date, CTX-II is the leading biomarker for osteoarthritis in terms of one that may be predictive of patients who are at risk for progression,” Dr. Clifton O. Bingham III, the study's lead author and a rheumatologist at Johns Hopkins University, Baltimore, said.

Whether these changes in biomarkers will translate into a later clinically relevant change in joint preservation is unknown. “The fact that we are able to now show that certain treatments can affect this biomarker is really a very important piece for us in order to move forward in the development of therapeutics,” said Dr. Bingham, who reported receiving consulting fees from Procter & Gamble Pharmaceuticals Inc., maker of risedronate (Actonel).

The study was conducted at 42 sites in North America and at 44 sites in the European Union (Arthritis Rheum. 2006;54:3494–507). Patients were randomized to receive placebo or oral risedronate in dosages of 5 mg/day, 15 mg/day, 35 mg/week (Europe only), or 50 mg/week (North America only).

Patients aged 40–80 years were screened for inclusion if they had signal knee pain resulting from osteoarthritis (OA) most days during at least 1 month in a 3-month period, and had one of the following: morning knee stiffness lasting more than 30 minutes, or knee crepitus according to the American College of Rheumatology criteria for knee OA.

Patients were excluded if they had known inflammatory arthritis; body mass index (kg/m

All patients underwent radiography of the knee to confirm OA. For inclusion, patients had to have at least one osteophyte and minimal joint space width of 2–4 mm, inclusive, in the medial tibiofemoral compartment, and a medial compartment that was narrower than the lateral. Radiographic assessment was performed at baseline, 1 year, and 2 years.

Nonnarcotic analgesics, NSAIDs, or COX-2 inhibitors were allowed and monitored during the study. Patients underwent a stepped reduction and washout period for these medications prior to study visits, including the baseline visit. Patients were provided with 500 mg acetaminophen (North America) or paracetamol (Europe) and 50 mg diclofenac to be used as needed from 5 to 3 days prior to a visit. All pain medications were stopped 2 days prior to a visit.

The two primary end points were the effect of risedronate on structure and symptoms compared with placebo after 2 years. Patient symptoms were measured by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and by Patient Global Assessment (PGA) scores. Structure was assessed by measuring joint-space narrowing in the medial tibiofemoral compartment.

Joint-space narrowing of the target knee was evaluated at the narrowest point in the medial tibiofemoral compartment at baseline and at 1 and 2 years follow-up. Radiographs were performed using a semiflexed view of the knee (fluoroscopically assisted). Radiographs were obtained at 13 regional radiographic facilities in Europe and 12 in the United States. All radiographs were sent to a quality control center in Amsterdam for review and then to the central analysis facility in London, where films were digitized and semiautomated computer measurements of minimal medial joint-space width were performed. The test-retest standard deviation—the difference between radiographs obtained 2 days apart—for this technique was approximately 0.2 mm.

Urine samples were also collected at baseline and at 6 months, 12 months, and 24 months. Samples were analyzed for N-terminal crosslinking telopeptide of type I collagen (NTX-I) to assess bone resorption and for CTX-II.

In the North American cohort, 301 participants were randomized to placebo, 306 to 5 mg/day risedronate, 302 to 15 mg/day, and 314 to 50 mg/week. In the European cohort, 312 participants were randomized to placebo, 322 to 5 mg/day risedronate, 307 to 15 mg/day, and 310 to 35 mg/week.

“In both the European and North American studies, no significant differences between treatment groups were noted in the mean change from baseline in total WOMAC score, scores for WOMAC components, or PGA scores,” the researchers said. Notably, those patients treated with placebo had a mean reduction of about 20% from baseline in total WOMAC scores.

“In all treatment groups, including the placebo, there was a clinically detectable improvement in pain that occurred at the 6-month point and was maintained over 2 years,” said Dr. Bingham. The results for the placebo patients highlight the importance of accounting for placebo benefit in osteoarthritis studies. Not only did placebo improvement occur, but it was maintained over time.

So either improvement is part of the natural course of the disease or there is a clinical benefit simply in entering a clinical trial. Regardless, this effect needs to be taken into consideration in designing future osteoarthritis trials, said Dr. Bingham, who is also with the division of allergy and immunology at Johns Hopkins University.

In terms of structure, 13% of participants had radiographic progression. There were no statistically significant differences in any treatment group in either cohort.

“When you looked at the people who were showing what was unequivocally progression … there was no drug effect that was demonstrated but interestingly that group of people was only a very small percentage of the entire study population,” said Dr. Bingham.

The radiographic findings also have implications for future trial design: If only a small number of people are going to show substantial worsening in terms of joint structure, then—in order to study an OA drug by looking at structure as an outcome—greater numbers of patients are needed to be able to demonstrate a potential treatment effect, he said.

In both cohorts, a dose-dependent decrease in the level of NTX-I was observed within 6 months for those on risedronate, and it continued through 24 months. The mean percent change from baseline to 24 months for all dosages of risedronate was statistically different from the placebo group. In the North American group, those on placebo had a mean increase in NTX-I of 7.3%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 50 mg/week had NTX-I level decreases of 21.6%, 39.2%, and 29.2%, respectively. In the European cohort, those on placebo had a mean increase in NTX-I of 3.0%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 35 mg/week had NTX-I level decreases of 29.0%, 41.7%, and 28.2%, respectively.

The results for CTX-II levels were similar, with those on placebo having increases over 24 months, whereas those on risedronate had early decreases. At 15 mg/day risedronate, reductions of 17.9% and 19.6% from baseline were seen in North American and European patients respectively. In comparison, the North American and European placebo groups had increases of CTX-II levels of 26.3% and 10.1%, respectively.

The biomarker results suggest—from a pathobiologic perspective—that an agent that acts on subchondral bone, interrupts the turnover of bone, and improves bone structure can consequently improve cartilage stability. This suggests a fundamental interaction between bone and cartilage. This could be important because treatments already are available that interrupt bone turnover.

These study results indicate that “potentially the bone is an important therapeutic target in patients with osteoarthritis,” said Dr. Bingham.

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).

The increased lymphoma risk seen in patients with severe rheumatoid arthritis appears to involve a specific subtype of diffuse large B-cell lymphoma that arises from activated peripheral blood B cells.

Dr. Eva Baecklund of Akademiska Hospital in Uppsala, Sweden, and her associates identified 139 RA patients with diffuse large B-cell lymphoma from within a population-based case-control study of 378 RA patients with lymphoma. The RA patients with lymphoma were originally identified from linkage of the nationwide Swedish Inpatient Register with the Swedish Cancer Register.

Diffuse large B-cell lymphoma (DLBCL) can be classified into two major subtypes based on gene expression profiles. One tumor subtype expresses genes characteristic of germinal center (GC) B cells. The other tumor subtype (non-GC) expresses genes seen in activated peripheral blood B cells.

In this study, the cases of DLBCL were classified as GC or non-GC based on immunohistochemistry using a three-marker system. CD10, Bcl-6, and interferon regulatory factor 4 (IRF-4, also known as multiple myeloma oncogene 1) were tested. Staining of 30% or more of tumor cells was defined as positive.

Investigators reviewed the original slides and paraffin-embedded lymphoma tissues from pathology laboratories and reclassified the tumors according to the World Health Organization classification system. Immunohistochemical staining for CD10, Bcl-6, and IRF-4 antibodies was performed on paraffin-imbedded tissue. Gene expression profiling could not be performed because of the lack of frozen tissue.

All tumors that stained positive for CD10, whether positive or negative for Bcl-6, were classified as GC-like. Tumors that stained negative for both CD10 and Bcl-6 were classified as non-GC-like. Tumors that showed negative staining for CD10 but positive staining for Bcl-6 were tested for IRF-4. CD10-negative/Bcl-6-positive tumor cells that showed positive staining for IRF-4 were classified as non-GC subtype, and those that showed negative IRF-4 staining were classified as GC subtype.

DLBCL tumors from 42 patients (30%) were identified as GC subtype, and DLBCL tumors from 97 patients (70%) were identified as non-GC subtype. Women were the majority in both the GC and non-GC groups (57% and 60%, respectively). The mean age of RA onset was around 50 years in each group. The mean age at lymphoma diagnosis was 70 years (range: 32–84 years) for patients with GC subtype DLBCL, compared with 71 years (range: 48–89) for patients with non-GC subtype DLBCL.

There were no significant differences between the two groups in RA functional class, disease activity, or RA treatment. Compared with patients with GC subtype DLBCL tumors, a higher proportion of patients with non-GC subtype DLBCL tumors had RA disease activity in functional classes III and IV, but the trend did not reach statistical significance (P = .07).

Tumor stage differed significantly in patients with non-GC subtype tumors, compared with those with GC subtype tumors (P = .005). A higher proportion of patients with non-GC subtype DLBCL tumors (60 patients; 64%) had disseminated lymphoma (Ann Arbor stage IV), compared with patients with GC DLBCL tumors (15 patients; 38%). Among patients in whom extranodal involvement could be assessed, significantly more patients with non-GC DLCBL tumors (72/93; 77%) had extranodal involvement, compared with patients with GC DLCBL tumors (25/39; 64%; P = .03).

In RA patients with advanced lymphoma, the prognosis was worse if the tumor subtype was non-GC.

The 5-year overall survival was 33% for patients with GC-subtype DLCBL tumors, compared with 16% for patients with non-GC subtype DLCBL tumors, the investigators wrote (Arthritis Rheum. 2006;12:3774–81).

PRAGUE — In patients with osteoarthritis—and even in healthy subjects—standard walking shoes result in significantly more knee adduction compared with barefoot walking or walking with a specially designed “unloading” shoe, reported Dr. Najia Shakoor in a poster at the 2006 World Congress on Osteoarthritis.

“High [dynamic] loading has been associated with both the presence and progression of OA,” Dr. Shakoor commented in an interview, noting that increased loading results in increased adduction.

In a previous study, Dr. Shakoor and colleagues from Rush Medical College, Chicago, demonstrated that in subjects with knee OA, walking barefoot significantly decreases peak external knee adduction compared with walking in standard walking shoes (Arthritis Rheum. 2006;54:2923–7).

The group subsequently designed a shoe to mimic the unloading characteristics of barefoot walking and tested it in a cohort of 26 healthy subjects.

The 18 females and 8 males, with a mean age of 42 years, received gait evaluations while wearing their self-selected normal walking shoes.

All subjects also had a gait analysis while walking barefoot, and 19 were analyzed while they wore the specially designed unloading shoes. “The shoes are very flat and thin-soled, with a soft upper that wraps around the foot like a glove,” said Dr. Shakoor.

“There are slit lines in the sole to conform to the major natural flexion points of the foot.”

Although a provisional patent has been filed and the group hopes the shoes will one day be marketed as a therapeutic intervention, they do not currently have any company affiliations.

Overall, a significant 13% reduction in subjects' external knee adduction was noted during their walking while barefoot and with the unloading shoes, compared with walking in their normal walking shoes.

The researchers also have data showing similar unloading effects of the shoes in patients with OA, according to Dr. Shakoor, speaking at the conference, which was sponsored by the Osteoarthritis Research Society International.

A man undergoes gait analysis in his normal walking shoes. Courtesy Dr. Najia Shakoor

PRAGUE — In patients with osteoarthritis—and even in healthy subjects—standard walking shoes result in significantly more knee adduction compared with barefoot walking or walking with a specially designed “unloading” shoe, reported Dr. Najia Shakoor in a poster at the 2006 World Congress on Osteoarthritis.

“High [dynamic] loading has been associated with both the presence and progression of OA,” Dr. Shakoor commented in an interview, noting that increased loading results in increased adduction.

In a previous study, Dr. Shakoor and colleagues from Rush Medical College, Chicago, demonstrated that in subjects with knee OA, walking barefoot significantly decreases peak external knee adduction compared with walking in standard walking shoes (Arthritis Rheum. 2006;54:2923–7).

The group subsequently designed a shoe to mimic the unloading characteristics of barefoot walking and tested it in a cohort of 26 healthy subjects.

The 18 females and 8 males, with a mean age of 42 years, received gait evaluations while wearing their self-selected normal walking shoes.

All subjects also had a gait analysis while walking barefoot, and 19 were analyzed while they wore the specially designed unloading shoes. “The shoes are very flat and thin-soled, with a soft upper that wraps around the foot like a glove,” said Dr. Shakoor.

“There are slit lines in the sole to conform to the major natural flexion points of the foot.”

Although a provisional patent has been filed and the group hopes the shoes will one day be marketed as a therapeutic intervention, they do not currently have any company affiliations.

Overall, a significant 13% reduction in subjects' external knee adduction was noted during their walking while barefoot and with the unloading shoes, compared with walking in their normal walking shoes.

The researchers also have data showing similar unloading effects of the shoes in patients with OA, according to Dr. Shakoor, speaking at the conference, which was sponsored by the Osteoarthritis Research Society International.

A man undergoes gait analysis in his normal walking shoes. Courtesy Dr. Najia Shakoor

PRAGUE — In patients with osteoarthritis—and even in healthy subjects—standard walking shoes result in significantly more knee adduction compared with barefoot walking or walking with a specially designed “unloading” shoe, reported Dr. Najia Shakoor in a poster at the 2006 World Congress on Osteoarthritis.

“High [dynamic] loading has been associated with both the presence and progression of OA,” Dr. Shakoor commented in an interview, noting that increased loading results in increased adduction.

In a previous study, Dr. Shakoor and colleagues from Rush Medical College, Chicago, demonstrated that in subjects with knee OA, walking barefoot significantly decreases peak external knee adduction compared with walking in standard walking shoes (Arthritis Rheum. 2006;54:2923–7).

The group subsequently designed a shoe to mimic the unloading characteristics of barefoot walking and tested it in a cohort of 26 healthy subjects.

The 18 females and 8 males, with a mean age of 42 years, received gait evaluations while wearing their self-selected normal walking shoes.

All subjects also had a gait analysis while walking barefoot, and 19 were analyzed while they wore the specially designed unloading shoes. “The shoes are very flat and thin-soled, with a soft upper that wraps around the foot like a glove,” said Dr. Shakoor.

“There are slit lines in the sole to conform to the major natural flexion points of the foot.”

Although a provisional patent has been filed and the group hopes the shoes will one day be marketed as a therapeutic intervention, they do not currently have any company affiliations.

Overall, a significant 13% reduction in subjects' external knee adduction was noted during their walking while barefoot and with the unloading shoes, compared with walking in their normal walking shoes.

The researchers also have data showing similar unloading effects of the shoes in patients with OA, according to Dr. Shakoor, speaking at the conference, which was sponsored by the Osteoarthritis Research Society International.

A man undergoes gait analysis in his normal walking shoes. Courtesy Dr. Najia Shakoor

PRAGUE — Individually calibrated shoes that provide dynamic wedging can significantly improve pain and function in patients with knee osteoarthritis—sometimes immediately, according to a study reported Dr. Yuval Ran at the 2006 World Congress on Osteoarthritis.

“We have clearly demonstrated clinical efficacy. Immediate relief of pain in some patients enabled them to walk painlessly during real-life activity thus reacquiring neuromuscular skills and balance,” he said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Ran, from the Assaf Harofeh Medical Center in Tel Aviv, has been treating patients with the APOS system footwear from Atlantic Prosthetic Orthotic Services Ltd. in Kilcolgan, Ireland, for about 2 years, he said, adding that he has no conflict of interest to disclose.

Unlike other active osteoarthritis (OA) interventions, which usually require intensive physical therapy programs and result in low compliance, the APOS system, which involves semispherical, individually calibrated implants in special footwear, often relieves pain immediately and thus results in extraordinary compliance, he said.

“Many patients wear the shoes all the time because we can't instruct them not to wear something that relieves pain,” he said, noting that the implants are designed to improve age-related loss in neuromuscular control and resulting muscle-weakness and stress on the knee joint.

The semispherical rubber devices that are placed on the soles of the shoes at the hindfoot and midfoot can move medially and laterally and may be individually adjusted in order to balance loading, he explained.

In a randomized trial of 61 knee OA patients, mean age 66 years, treated for 8 weeks with the APOS implants or placebo, Dr. Ran and his colleagues noted a “highly significant” 70% decrease in pain in the treated group, measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and a 33% improvement in function according to the Aggregated Locomotor Function (ALF) scale, compared with no improvements in the control group.

Patients were advised to start the treatment with 10 minutes of indoor wear, building up to 30 minutes of outdoor walking—however, he said the majority of patients chose to wear the shoes most of the time because of the pain relief provided. Evaluation was performed at baseline, 4 weeks, and 8 weeks.

Patients also were supervised four times during the study to make adjustments to the shoes, if necessary. Patients in the placebo arm wore shoes that looked identical except without the spheres on the soles.

The wedging implants are designed to reduce age-related stress on the knee.

Couple with OA demonstrate the footwear with wedging. Photos courtesy Dr. Yuval Ran/Dr. Avi Elbaz/Dr. Amit Mor

PRAGUE — Individually calibrated shoes that provide dynamic wedging can significantly improve pain and function in patients with knee osteoarthritis—sometimes immediately, according to a study reported Dr. Yuval Ran at the 2006 World Congress on Osteoarthritis.

“We have clearly demonstrated clinical efficacy. Immediate relief of pain in some patients enabled them to walk painlessly during real-life activity thus reacquiring neuromuscular skills and balance,” he said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Ran, from the Assaf Harofeh Medical Center in Tel Aviv, has been treating patients with the APOS system footwear from Atlantic Prosthetic Orthotic Services Ltd. in Kilcolgan, Ireland, for about 2 years, he said, adding that he has no conflict of interest to disclose.

Unlike other active osteoarthritis (OA) interventions, which usually require intensive physical therapy programs and result in low compliance, the APOS system, which involves semispherical, individually calibrated implants in special footwear, often relieves pain immediately and thus results in extraordinary compliance, he said.

“Many patients wear the shoes all the time because we can't instruct them not to wear something that relieves pain,” he said, noting that the implants are designed to improve age-related loss in neuromuscular control and resulting muscle-weakness and stress on the knee joint.

The semispherical rubber devices that are placed on the soles of the shoes at the hindfoot and midfoot can move medially and laterally and may be individually adjusted in order to balance loading, he explained.

In a randomized trial of 61 knee OA patients, mean age 66 years, treated for 8 weeks with the APOS implants or placebo, Dr. Ran and his colleagues noted a “highly significant” 70% decrease in pain in the treated group, measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and a 33% improvement in function according to the Aggregated Locomotor Function (ALF) scale, compared with no improvements in the control group.

Patients were advised to start the treatment with 10 minutes of indoor wear, building up to 30 minutes of outdoor walking—however, he said the majority of patients chose to wear the shoes most of the time because of the pain relief provided. Evaluation was performed at baseline, 4 weeks, and 8 weeks.

Patients also were supervised four times during the study to make adjustments to the shoes, if necessary. Patients in the placebo arm wore shoes that looked identical except without the spheres on the soles.

The wedging implants are designed to reduce age-related stress on the knee.

Couple with OA demonstrate the footwear with wedging. Photos courtesy Dr. Yuval Ran/Dr. Avi Elbaz/Dr. Amit Mor

PRAGUE — Individually calibrated shoes that provide dynamic wedging can significantly improve pain and function in patients with knee osteoarthritis—sometimes immediately, according to a study reported Dr. Yuval Ran at the 2006 World Congress on Osteoarthritis.

“We have clearly demonstrated clinical efficacy. Immediate relief of pain in some patients enabled them to walk painlessly during real-life activity thus reacquiring neuromuscular skills and balance,” he said at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Ran, from the Assaf Harofeh Medical Center in Tel Aviv, has been treating patients with the APOS system footwear from Atlantic Prosthetic Orthotic Services Ltd. in Kilcolgan, Ireland, for about 2 years, he said, adding that he has no conflict of interest to disclose.

Unlike other active osteoarthritis (OA) interventions, which usually require intensive physical therapy programs and result in low compliance, the APOS system, which involves semispherical, individually calibrated implants in special footwear, often relieves pain immediately and thus results in extraordinary compliance, he said.

“Many patients wear the shoes all the time because we can't instruct them not to wear something that relieves pain,” he said, noting that the implants are designed to improve age-related loss in neuromuscular control and resulting muscle-weakness and stress on the knee joint.

The semispherical rubber devices that are placed on the soles of the shoes at the hindfoot and midfoot can move medially and laterally and may be individually adjusted in order to balance loading, he explained.

In a randomized trial of 61 knee OA patients, mean age 66 years, treated for 8 weeks with the APOS implants or placebo, Dr. Ran and his colleagues noted a “highly significant” 70% decrease in pain in the treated group, measured with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and a 33% improvement in function according to the Aggregated Locomotor Function (ALF) scale, compared with no improvements in the control group.

Patients were advised to start the treatment with 10 minutes of indoor wear, building up to 30 minutes of outdoor walking—however, he said the majority of patients chose to wear the shoes most of the time because of the pain relief provided. Evaluation was performed at baseline, 4 weeks, and 8 weeks.

Patients also were supervised four times during the study to make adjustments to the shoes, if necessary. Patients in the placebo arm wore shoes that looked identical except without the spheres on the soles.

The wedging implants are designed to reduce age-related stress on the knee.

Couple with OA demonstrate the footwear with wedging. Photos courtesy Dr. Yuval Ran/Dr. Avi Elbaz/Dr. Amit Mor

Pharmaceutic management or physical therapy for older adult knee-pain patients yielded significantly greater short-term pain reduction than written and oral advice on coping with knee pain, according to a randomized clinical trial.

The trial (BMJ 2006 Oct. 20 [Epub doi:10.1136/bmj.38977.590752.0B]) randomized 325 knee-pain patients 55 years of age and older from North Staffordshire (England), into equal-sized groups—one received up to six 20-minute sessions of physical therapy over 10 weeks with additional home exercises, another received advice from a community pharmacist in up to six 20-minute meetings, and a control group received a booklet and a telephone call from a rheumatology nurse.

Researchers, led by Dr. Elaine Hay, a professor in community rheumatology at the Primary Care Musculoskeletal Research Centre, Keele University, chiefly measured improvements on the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) at 3, 6, and 12 months.

At 3 months, the researchers found that the intervention groups both had shown a significantly greater improvement than the control group on the 20-point WOMAC pain scale.

The pharmacy group had improved by a mean of 1.59 points to 7.49, the physiotherapy group by a mean 1.56 to 7.36, compared with the control group's improvement of 0.41 to 8.99.

By 6 months, neither intervention group was showing a significant improvement over the control group.

On the 68-point WOMAC physical function scale, the physiotherapy group improved by a mean score of 4.79 points to 24.27 at 3 months, significantly better than the control group's improvement of 0.80 to 30.18, the trial found. The difference was not sustained to 6 or 12 months.

The researchers added, however, that the physical therapy group consulted general practitioners less frequently, and the pharmacy and physical therapy groups took fewer NSAIDs than the control group. The pharmacy group did take significantly more analgesics, however.

“Interventions by pharmacists have been shown to favorably influence prescribing to reduce adverse drug reactions, improve the appropriateness of drug use, reduce drug costs, and improve compliance in a range of conditions,” the authors wrote.

“Our trial adds to this evidence by showing that evidence-based care for adults over 55 with knee pain, delivered by primary care pharmacists and physiotherapists, results in short-term improvements in health outcome, reduction in use of nonsteroidal anti-inflammatory drugs, and high patient satisfaction,” the investigators continued.

The researchers cited as a potential weakness of the trial their “lack of information about patients' adherence to treatment, which is likely to be an important determinant of clinical outcome.”

Pharmaceutic management or physical therapy for older adult knee-pain patients yielded significantly greater short-term pain reduction than written and oral advice on coping with knee pain, according to a randomized clinical trial.

The trial (BMJ 2006 Oct. 20 [Epub doi:10.1136/bmj.38977.590752.0B]) randomized 325 knee-pain patients 55 years of age and older from North Staffordshire (England), into equal-sized groups—one received up to six 20-minute sessions of physical therapy over 10 weeks with additional home exercises, another received advice from a community pharmacist in up to six 20-minute meetings, and a control group received a booklet and a telephone call from a rheumatology nurse.

Researchers, led by Dr. Elaine Hay, a professor in community rheumatology at the Primary Care Musculoskeletal Research Centre, Keele University, chiefly measured improvements on the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) at 3, 6, and 12 months.

At 3 months, the researchers found that the intervention groups both had shown a significantly greater improvement than the control group on the 20-point WOMAC pain scale.

The pharmacy group had improved by a mean of 1.59 points to 7.49, the physiotherapy group by a mean 1.56 to 7.36, compared with the control group's improvement of 0.41 to 8.99.

By 6 months, neither intervention group was showing a significant improvement over the control group.

On the 68-point WOMAC physical function scale, the physiotherapy group improved by a mean score of 4.79 points to 24.27 at 3 months, significantly better than the control group's improvement of 0.80 to 30.18, the trial found. The difference was not sustained to 6 or 12 months.

The researchers added, however, that the physical therapy group consulted general practitioners less frequently, and the pharmacy and physical therapy groups took fewer NSAIDs than the control group. The pharmacy group did take significantly more analgesics, however.

“Interventions by pharmacists have been shown to favorably influence prescribing to reduce adverse drug reactions, improve the appropriateness of drug use, reduce drug costs, and improve compliance in a range of conditions,” the authors wrote.

“Our trial adds to this evidence by showing that evidence-based care for adults over 55 with knee pain, delivered by primary care pharmacists and physiotherapists, results in short-term improvements in health outcome, reduction in use of nonsteroidal anti-inflammatory drugs, and high patient satisfaction,” the investigators continued.

The researchers cited as a potential weakness of the trial their “lack of information about patients' adherence to treatment, which is likely to be an important determinant of clinical outcome.”

Pharmaceutic management or physical therapy for older adult knee-pain patients yielded significantly greater short-term pain reduction than written and oral advice on coping with knee pain, according to a randomized clinical trial.

The trial (BMJ 2006 Oct. 20 [Epub doi:10.1136/bmj.38977.590752.0B]) randomized 325 knee-pain patients 55 years of age and older from North Staffordshire (England), into equal-sized groups—one received up to six 20-minute sessions of physical therapy over 10 weeks with additional home exercises, another received advice from a community pharmacist in up to six 20-minute meetings, and a control group received a booklet and a telephone call from a rheumatology nurse.

Researchers, led by Dr. Elaine Hay, a professor in community rheumatology at the Primary Care Musculoskeletal Research Centre, Keele University, chiefly measured improvements on the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) at 3, 6, and 12 months.

At 3 months, the researchers found that the intervention groups both had shown a significantly greater improvement than the control group on the 20-point WOMAC pain scale.

The pharmacy group had improved by a mean of 1.59 points to 7.49, the physiotherapy group by a mean 1.56 to 7.36, compared with the control group's improvement of 0.41 to 8.99.

By 6 months, neither intervention group was showing a significant improvement over the control group.

On the 68-point WOMAC physical function scale, the physiotherapy group improved by a mean score of 4.79 points to 24.27 at 3 months, significantly better than the control group's improvement of 0.80 to 30.18, the trial found. The difference was not sustained to 6 or 12 months.

The researchers added, however, that the physical therapy group consulted general practitioners less frequently, and the pharmacy and physical therapy groups took fewer NSAIDs than the control group. The pharmacy group did take significantly more analgesics, however.

“Interventions by pharmacists have been shown to favorably influence prescribing to reduce adverse drug reactions, improve the appropriateness of drug use, reduce drug costs, and improve compliance in a range of conditions,” the authors wrote.

“Our trial adds to this evidence by showing that evidence-based care for adults over 55 with knee pain, delivered by primary care pharmacists and physiotherapists, results in short-term improvements in health outcome, reduction in use of nonsteroidal anti-inflammatory drugs, and high patient satisfaction,” the investigators continued.

The researchers cited as a potential weakness of the trial their “lack of information about patients' adherence to treatment, which is likely to be an important determinant of clinical outcome.”

TORONTO — Most cases of septic arthritis resulting from arthroscopic joint surgery can be controlled with conservative treatment comprising prolonged IV antibiotics and surgical drainage, as long as there is no bone involvement and the affected joint has not been compromised, Dr. Carla Vizzotti said at the annual meeting of the Infectious Diseases Society of America.

Although postarthroscopic septic arthritis (PASA) is an infrequent condition, it can result in significant morbidity if not properly treated and can interfere with patients' recovery, Dr. Vizzotti said in a poster presentation.

Because medical and surgical therapies for the condition are not standardized, Dr. Vizzotti and colleagues at the Fundación Centro de Estudios Infectológicos in Buenos Aires, conducted a retrospective investigation to identify optimal management strategies.

The investigators reviewed the records of 61 patients treated for PASA between November 1991 and November 2005. Patients were included in the investigation if, following a diagnostic or operative arthroscopic procedure, they developed at least one of the clinical signs of arthritis—increased pain, swelling, and warmth—in the affected joint, and/or developed a fever and had a positive culture or grossly or macroscopically purulent synovial fluid.

The mean age of the patients was 37.2 years and the mean follow-up period was 32.5 months.

Among the 61 patients, there were a total of 63 infections, including 58 in the knee, 4 in the shoulder, and 1 in the ankle. Of the 63 infections, 41 occurred in patients who underwent arthroscopic ligament repair that included a graft or implant insertion.

In terms of clinical presentation, fever and pain were each noted in 41 cases; red skin, swelling, and/or warmth were present in 53 cases; fistula and purulent discharges were each noted in 9 cases; functional impotence occurred in 10 cases; and an elevated erythrocyte sedimentation rate (greater than 50 mm/hour) was reported in 7 cases.

Microbiologic data were available for all but two of the infections.

Gram-positive cocci were implicated in 39 of the infections, gram-negative bacilli were identified in 9 of them, and negative cultures were noted in 13, Dr. Vizzotti reported. All of the patients received antibiotic therapy—primarily β-lactams—for a mean of 9.2 weeks.

Surgical drainage was used in 48 of the 63 infections, including arthroscopic irrigation and lavage of the joint in 38 cases, lavage of the joint via arthrotomy in 2 cases, needle aspiration in 6 cases, and combined needle aspiration and arthroscopic irrigation in 2 cases.

Of the study population, only four patients required removal of the grafts or implants that were used to repair the ligaments because of joint instability and/or bone involvement, Dr. Vizzotti said.

Treatment resulted in cure or significant improvement in 97% of the patients.

Three patients experienced complications of infection, including osteomyelitis in two patients and toxic shock syndrome in one.

The findings of the study suggest that most patients with postarthroscopic septic arthritis can be successfully treated with a combination of antibiotics and joint irrigation and lavage, Dr. Vizzotti stated.

Additionally, “as long as the joint is stable and functioning, and if there is no bone involvement, it is uncommon for a patient to require graft or implant removal,” she said.

Dr. Vizzotti reported having no financial disclosures relative to her presentation.

TORONTO — Most cases of septic arthritis resulting from arthroscopic joint surgery can be controlled with conservative treatment comprising prolonged IV antibiotics and surgical drainage, as long as there is no bone involvement and the affected joint has not been compromised, Dr. Carla Vizzotti said at the annual meeting of the Infectious Diseases Society of America.

Although postarthroscopic septic arthritis (PASA) is an infrequent condition, it can result in significant morbidity if not properly treated and can interfere with patients' recovery, Dr. Vizzotti said in a poster presentation.

Because medical and surgical therapies for the condition are not standardized, Dr. Vizzotti and colleagues at the Fundación Centro de Estudios Infectológicos in Buenos Aires, conducted a retrospective investigation to identify optimal management strategies.

The investigators reviewed the records of 61 patients treated for PASA between November 1991 and November 2005. Patients were included in the investigation if, following a diagnostic or operative arthroscopic procedure, they developed at least one of the clinical signs of arthritis—increased pain, swelling, and warmth—in the affected joint, and/or developed a fever and had a positive culture or grossly or macroscopically purulent synovial fluid.

The mean age of the patients was 37.2 years and the mean follow-up period was 32.5 months.

Among the 61 patients, there were a total of 63 infections, including 58 in the knee, 4 in the shoulder, and 1 in the ankle. Of the 63 infections, 41 occurred in patients who underwent arthroscopic ligament repair that included a graft or implant insertion.

In terms of clinical presentation, fever and pain were each noted in 41 cases; red skin, swelling, and/or warmth were present in 53 cases; fistula and purulent discharges were each noted in 9 cases; functional impotence occurred in 10 cases; and an elevated erythrocyte sedimentation rate (greater than 50 mm/hour) was reported in 7 cases.

Microbiologic data were available for all but two of the infections.

Gram-positive cocci were implicated in 39 of the infections, gram-negative bacilli were identified in 9 of them, and negative cultures were noted in 13, Dr. Vizzotti reported. All of the patients received antibiotic therapy—primarily β-lactams—for a mean of 9.2 weeks.

Surgical drainage was used in 48 of the 63 infections, including arthroscopic irrigation and lavage of the joint in 38 cases, lavage of the joint via arthrotomy in 2 cases, needle aspiration in 6 cases, and combined needle aspiration and arthroscopic irrigation in 2 cases.

Of the study population, only four patients required removal of the grafts or implants that were used to repair the ligaments because of joint instability and/or bone involvement, Dr. Vizzotti said.

Treatment resulted in cure or significant improvement in 97% of the patients.

Three patients experienced complications of infection, including osteomyelitis in two patients and toxic shock syndrome in one.

The findings of the study suggest that most patients with postarthroscopic septic arthritis can be successfully treated with a combination of antibiotics and joint irrigation and lavage, Dr. Vizzotti stated.

Additionally, “as long as the joint is stable and functioning, and if there is no bone involvement, it is uncommon for a patient to require graft or implant removal,” she said.

Dr. Vizzotti reported having no financial disclosures relative to her presentation.

TORONTO — Most cases of septic arthritis resulting from arthroscopic joint surgery can be controlled with conservative treatment comprising prolonged IV antibiotics and surgical drainage, as long as there is no bone involvement and the affected joint has not been compromised, Dr. Carla Vizzotti said at the annual meeting of the Infectious Diseases Society of America.

Although postarthroscopic septic arthritis (PASA) is an infrequent condition, it can result in significant morbidity if not properly treated and can interfere with patients' recovery, Dr. Vizzotti said in a poster presentation.

Because medical and surgical therapies for the condition are not standardized, Dr. Vizzotti and colleagues at the Fundación Centro de Estudios Infectológicos in Buenos Aires, conducted a retrospective investigation to identify optimal management strategies.

The investigators reviewed the records of 61 patients treated for PASA between November 1991 and November 2005. Patients were included in the investigation if, following a diagnostic or operative arthroscopic procedure, they developed at least one of the clinical signs of arthritis—increased pain, swelling, and warmth—in the affected joint, and/or developed a fever and had a positive culture or grossly or macroscopically purulent synovial fluid.

The mean age of the patients was 37.2 years and the mean follow-up period was 32.5 months.

Among the 61 patients, there were a total of 63 infections, including 58 in the knee, 4 in the shoulder, and 1 in the ankle. Of the 63 infections, 41 occurred in patients who underwent arthroscopic ligament repair that included a graft or implant insertion.

In terms of clinical presentation, fever and pain were each noted in 41 cases; red skin, swelling, and/or warmth were present in 53 cases; fistula and purulent discharges were each noted in 9 cases; functional impotence occurred in 10 cases; and an elevated erythrocyte sedimentation rate (greater than 50 mm/hour) was reported in 7 cases.

Microbiologic data were available for all but two of the infections.

Gram-positive cocci were implicated in 39 of the infections, gram-negative bacilli were identified in 9 of them, and negative cultures were noted in 13, Dr. Vizzotti reported. All of the patients received antibiotic therapy—primarily β-lactams—for a mean of 9.2 weeks.

Surgical drainage was used in 48 of the 63 infections, including arthroscopic irrigation and lavage of the joint in 38 cases, lavage of the joint via arthrotomy in 2 cases, needle aspiration in 6 cases, and combined needle aspiration and arthroscopic irrigation in 2 cases.

Of the study population, only four patients required removal of the grafts or implants that were used to repair the ligaments because of joint instability and/or bone involvement, Dr. Vizzotti said.

Treatment resulted in cure or significant improvement in 97% of the patients.

Three patients experienced complications of infection, including osteomyelitis in two patients and toxic shock syndrome in one.

The findings of the study suggest that most patients with postarthroscopic septic arthritis can be successfully treated with a combination of antibiotics and joint irrigation and lavage, Dr. Vizzotti stated.

Additionally, “as long as the joint is stable and functioning, and if there is no bone involvement, it is uncommon for a patient to require graft or implant removal,” she said.

Dr. Vizzotti reported having no financial disclosures relative to her presentation.

Knee joint osteoarthritis was significantly more common at 5 years after anterior cruciate ligament reconstruction in patients with patellar tendon autografts than in those with hamstring tendon autografts.

Dr. Matjaz Sajovic, along with researchers from the General Hospital Celje and the University of Ljubljana (Slovenia), conducted a prospective controlled study in which 64 patients with anterior cruciate ligament (ACL) rupture were randomized to reconstruction with hamstring tendon autografts (32) or patellar tendon autografts (32).

The comparative success of the two procedures and their associated incidence of early knee joint osteoarthritis were compared 5 years after surgery.

Among the 54 patients (85%) available for clinical and radiographic follow-up, there were no significant differences in graft rupture or contralateral ACL rupture in the 28 with hamstring tendon grafts and the 26 with patellar tendon grafts. Returns to preinjury activity levels were similar in the hamstring tendon group, 23 of 28, and in the patellar tendon group, 23 of 26. Among those with hamstring tendon autografts, grafts ruptured in two patients and contralateral ACLs ruptured in two. In those with patellar tendon autografts, grafts ruptured in two and contralateral ACLs ruptured in three (Am. J. Sports Med. 2006;34:1933–40).

Clinical and subjective test results were similar for the two groups; however, osteoarthritic changes significantly differed. Radiographic grade B knee joint osteoarthritis was present at the 5-year follow-up in 13 of the 26 patients (50%) with patellar tendon autografts and in 5 of the 28 patients (17%) with hamstring tendon autografts.

In other studies, osteoarthritis rates have been higher after meniscal resection. The authors attribute the lower rate in their study to significantly more (P = 0.027) subtotal meniscal resections performed in the hamstring tendon group, 12 of 28 patients, compared with the patellar tendon group, 4 of 26.

Further, medial meniscal injury was noted at reconstruction in 12 of 28 with hamstring tendon autografts and in 12 of 26 with patellar tendon autografts. Lateral meniscal injury was noted in six patients in each group. “It is difficult to obtain patients with solitary ACL tears without any other intra-articular lesions,” the investigators said.

At 5-year follow-up, radiographic evidence of knee joint osteoarthritis was significantly elevated in patients from the patellar tendon group (P = 0.012). This finding “emphasizes the hypothesis that the choice of the graft is crucial in the development of degenerative knee joint disease at 5 years after ACL reconstruction.”

Only one previous prospective, long-term study has compared the two autografts, but the findings excluded all patients with more than one-third meniscectomy and atraumatic graft failure. After 7 years, patellar tendon grafts were associated (P = 0.002) with more osteoarthritis (Am. J. Sports Med. 2005;33:1337–45).

Knee joint osteoarthritis was significantly more common at 5 years after anterior cruciate ligament reconstruction in patients with patellar tendon autografts than in those with hamstring tendon autografts.

Dr. Matjaz Sajovic, along with researchers from the General Hospital Celje and the University of Ljubljana (Slovenia), conducted a prospective controlled study in which 64 patients with anterior cruciate ligament (ACL) rupture were randomized to reconstruction with hamstring tendon autografts (32) or patellar tendon autografts (32).

The comparative success of the two procedures and their associated incidence of early knee joint osteoarthritis were compared 5 years after surgery.

Among the 54 patients (85%) available for clinical and radiographic follow-up, there were no significant differences in graft rupture or contralateral ACL rupture in the 28 with hamstring tendon grafts and the 26 with patellar tendon grafts. Returns to preinjury activity levels were similar in the hamstring tendon group, 23 of 28, and in the patellar tendon group, 23 of 26. Among those with hamstring tendon autografts, grafts ruptured in two patients and contralateral ACLs ruptured in two. In those with patellar tendon autografts, grafts ruptured in two and contralateral ACLs ruptured in three (Am. J. Sports Med. 2006;34:1933–40).

Clinical and subjective test results were similar for the two groups; however, osteoarthritic changes significantly differed. Radiographic grade B knee joint osteoarthritis was present at the 5-year follow-up in 13 of the 26 patients (50%) with patellar tendon autografts and in 5 of the 28 patients (17%) with hamstring tendon autografts.

In other studies, osteoarthritis rates have been higher after meniscal resection. The authors attribute the lower rate in their study to significantly more (P = 0.027) subtotal meniscal resections performed in the hamstring tendon group, 12 of 28 patients, compared with the patellar tendon group, 4 of 26.

Further, medial meniscal injury was noted at reconstruction in 12 of 28 with hamstring tendon autografts and in 12 of 26 with patellar tendon autografts. Lateral meniscal injury was noted in six patients in each group. “It is difficult to obtain patients with solitary ACL tears without any other intra-articular lesions,” the investigators said.

At 5-year follow-up, radiographic evidence of knee joint osteoarthritis was significantly elevated in patients from the patellar tendon group (P = 0.012). This finding “emphasizes the hypothesis that the choice of the graft is crucial in the development of degenerative knee joint disease at 5 years after ACL reconstruction.”

Only one previous prospective, long-term study has compared the two autografts, but the findings excluded all patients with more than one-third meniscectomy and atraumatic graft failure. After 7 years, patellar tendon grafts were associated (P = 0.002) with more osteoarthritis (Am. J. Sports Med. 2005;33:1337–45).

Knee joint osteoarthritis was significantly more common at 5 years after anterior cruciate ligament reconstruction in patients with patellar tendon autografts than in those with hamstring tendon autografts.

Dr. Matjaz Sajovic, along with researchers from the General Hospital Celje and the University of Ljubljana (Slovenia), conducted a prospective controlled study in which 64 patients with anterior cruciate ligament (ACL) rupture were randomized to reconstruction with hamstring tendon autografts (32) or patellar tendon autografts (32).

The comparative success of the two procedures and their associated incidence of early knee joint osteoarthritis were compared 5 years after surgery.

Among the 54 patients (85%) available for clinical and radiographic follow-up, there were no significant differences in graft rupture or contralateral ACL rupture in the 28 with hamstring tendon grafts and the 26 with patellar tendon grafts. Returns to preinjury activity levels were similar in the hamstring tendon group, 23 of 28, and in the patellar tendon group, 23 of 26. Among those with hamstring tendon autografts, grafts ruptured in two patients and contralateral ACLs ruptured in two. In those with patellar tendon autografts, grafts ruptured in two and contralateral ACLs ruptured in three (Am. J. Sports Med. 2006;34:1933–40).

Clinical and subjective test results were similar for the two groups; however, osteoarthritic changes significantly differed. Radiographic grade B knee joint osteoarthritis was present at the 5-year follow-up in 13 of the 26 patients (50%) with patellar tendon autografts and in 5 of the 28 patients (17%) with hamstring tendon autografts.

In other studies, osteoarthritis rates have been higher after meniscal resection. The authors attribute the lower rate in their study to significantly more (P = 0.027) subtotal meniscal resections performed in the hamstring tendon group, 12 of 28 patients, compared with the patellar tendon group, 4 of 26.

Further, medial meniscal injury was noted at reconstruction in 12 of 28 with hamstring tendon autografts and in 12 of 26 with patellar tendon autografts. Lateral meniscal injury was noted in six patients in each group. “It is difficult to obtain patients with solitary ACL tears without any other intra-articular lesions,” the investigators said.

At 5-year follow-up, radiographic evidence of knee joint osteoarthritis was significantly elevated in patients from the patellar tendon group (P = 0.012). This finding “emphasizes the hypothesis that the choice of the graft is crucial in the development of degenerative knee joint disease at 5 years after ACL reconstruction.”

Only one previous prospective, long-term study has compared the two autografts, but the findings excluded all patients with more than one-third meniscectomy and atraumatic graft failure. After 7 years, patellar tendon grafts were associated (P = 0.002) with more osteoarthritis (Am. J. Sports Med. 2005;33:1337–45).

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.

WASHINGTON — Baseline seropositivity for rheumatoid factor and anticyclic citrullinated peptide among patients with rheumatoid arthritis is associated with a more favorable response to treatment with rituximab, Dr. Paul P. Tak reported at the annual meeting of the American College of Rheumatology.

A post hoc analysis was undertaken to explore the relationship between baseline autoantibody status and rituximab therapy in patients who participated in the 24-week Randomized Evaluation of Long Term Efficacy of Rituximab (REFLEX) study, according to Dr. Tak of the University of Amsterdam.

In REFLEX, patients with long-standing RA who had inadequate responses to one or more anti-tumor necrosis factor (TNF)-α drugs were randomized to receive a course of intravenous rituximab, which consisted of two infusions of 1,000 mg each, separated by 2 weeks, or placebo. All patients also were on background methotrexate in doses of 10–25 mg/week.

Among 309 patients analyzed at week 24, there was a high degree of efficacy for those who were seropositive for either or both of the autoantibodies (see box). Baseline RF greater than 20 IU/mL and anti-CCP greater than 5 IU/mL were considered seropositive.

With regard to the lower level ACR 20 responses, seronegative patients on rituximab also achieved this level to a greater degree than did seronegative patients on placebo.

Seronegative patients receiving rituximab did not achieve greater ACR 50 or 70 responses, however. “This suggests that other mechanisms such as antigen presentation, T-cell co-stimulation, and cytokine release may account for low levels of response, with higher responses to rituximab therapy being mediated primarily by suppression of pathogenic autoantibodies,” Dr. Tak wrote in a poster session.

Dr. Tak disclosed that he received research grants and consulting fees from Roche Laborotories Inc.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.