Rheumatoid Arthritis

Two different cholesterol-lowering drugs reduce inflammation, disease activity, and aortic stiffness, and also improve endothelial function in patients with rheumatoid arthritis.

Participants in this randomized, double-blind crossover study included 20 patients with active rheumatoid arthritis (RA), defined as a disease activity score 28 (DAS28) greater than 3.5 and a C-reactive protein (CRP) level above 6 mg/L. None of the participants had cardiovascular disease, untreated hypertension, diabetes, elevated cholesterol, or renal disease, and none was a smoker.

Following a 2-week period during which all participants received placebo, they were given either 20 mg simvastatin or 10 mg ezetimibe for 6 weeks each, separated by a 6-week washout period before receiving the other drug for 6 weeks.

At baseline, the aortic pulse-wave velocity (PWV), a marker of aortic stiffness, was significantly higher in patients with RA than in 20 age-matched, healthy controls (9.42 m/s vs. 7.69 m/s, respectively). Likewise, flow-mediated dilatation (FMD) of the brachial artery, a marker of endothelial function, was reduced at baseline in RA patients, compared with controls. Both drugs reduced PWV while increasing FMD, but in neither case did the improvements achieve statistical significance.

Both drugs reduced total cholesterol significantly, from 5.3 mmol/L at baseline to 4.7 mmol/L for ezetimibe, and from a baseline of 5.4 mmol/L to 4.1 mmol/L for simvastatin. Likewise, both drugs reduced LDL cholesterol, from a baseline value of 3.08 mmol/L to 2.53 mmol/L for ezetimibe, and from a baseline of 3.18 mmol/L to 1.95 mmol/L for simvastatin.

Improvements—albeit less statistically significant ones—were seen in two markers of inflammation on both drugs. The erythrocyte sedimentation rate (ESR) dropped from a baseline of 18.2 mm/hour to 12.9 mm/hour for ezetimibe, and from a baseline of 18.6 mm/hour to 13.8 mm/hour for simvastatin. C-reactive protein (CRP) dropped from a baseline of 14.2 mg/L to 8.8 mg/L for ezetimibe, and from a baseline of 15.3 mg/L to 10.3 mg/L for simvastatin.

The patients' disease activity score also decreased somewhat, from a DAS28 of 4.41 at baseline to 3.86 for ezetimibe, and from a baseline DAS28 of 4.65 to 3.98 for simvastatin (J. Am. Coll. Cardiol. 2007;50:852-8).

Because two cholesterol-lowering agents operating by two different mechanisms each had these effects, it appears that it was the reduction in cholesterol itself that was responsible for reducing aortic stiffness and endothelial function, wrote Kaisa M. Mäki-Petäjä and her colleagues at the University of Cambridge (England).

And because the agents also reduced ESR and CRP—both markers of inflammation—as well as the rheumatoid arthritis composite DAS28, the investigators suggested that cholesterol-reducing therapies may benefit RA patients. These agents are well tolerated, improve clinical outcome in patients at risk for heart disease, and reduce surrogates of cardiovascular risk.

The investigators acknowledged, however, that future studies will be needed to establish whether reducing arterial stiffness and improving endothelial function with drugs intended to reduce hyperlipidemia will translate into an overall improvement in cardiovascular outcome in patients with RA.

The effects of simvastatin and ezetimibe differed significantly in a number of parameters. Simvastatin was better at reducing total cholesterol, LDL cholesterol, and oxidized LDL cholesterol. But they were equally effective in all other measures, including reducing inflammatory markers and aortic PWV, and increasing FMD. They were also equally effective in improving the tender-joints count and the swollen-joints count, the authors wrote.

Throughout the study, patients remained on their RA therapy, which consisted of methotrexate in 13 patients, NSAIDs in 14, prednisolone in nine, and other disease-modifying drugs in seven. In all, 18 patients took two or more drugs concomitantly and none was off RA drugs completely.

Ms. Mäki-Petäjä disclosed that her doctoral studies are funded by GlaxoSmithKline Inc., and one of the other investigators on the study disclosed receiving funding from Pfizer. Neither company is involved in marketing simvastatin or ezetimibe, both of which are manufactured by Merck & Co.

Two different cholesterol-lowering drugs reduce inflammation, disease activity, and aortic stiffness, and also improve endothelial function in patients with rheumatoid arthritis.

Participants in this randomized, double-blind crossover study included 20 patients with active rheumatoid arthritis (RA), defined as a disease activity score 28 (DAS28) greater than 3.5 and a C-reactive protein (CRP) level above 6 mg/L. None of the participants had cardiovascular disease, untreated hypertension, diabetes, elevated cholesterol, or renal disease, and none was a smoker.

Following a 2-week period during which all participants received placebo, they were given either 20 mg simvastatin or 10 mg ezetimibe for 6 weeks each, separated by a 6-week washout period before receiving the other drug for 6 weeks.

At baseline, the aortic pulse-wave velocity (PWV), a marker of aortic stiffness, was significantly higher in patients with RA than in 20 age-matched, healthy controls (9.42 m/s vs. 7.69 m/s, respectively). Likewise, flow-mediated dilatation (FMD) of the brachial artery, a marker of endothelial function, was reduced at baseline in RA patients, compared with controls. Both drugs reduced PWV while increasing FMD, but in neither case did the improvements achieve statistical significance.

Both drugs reduced total cholesterol significantly, from 5.3 mmol/L at baseline to 4.7 mmol/L for ezetimibe, and from a baseline of 5.4 mmol/L to 4.1 mmol/L for simvastatin. Likewise, both drugs reduced LDL cholesterol, from a baseline value of 3.08 mmol/L to 2.53 mmol/L for ezetimibe, and from a baseline of 3.18 mmol/L to 1.95 mmol/L for simvastatin.

Improvements—albeit less statistically significant ones—were seen in two markers of inflammation on both drugs. The erythrocyte sedimentation rate (ESR) dropped from a baseline of 18.2 mm/hour to 12.9 mm/hour for ezetimibe, and from a baseline of 18.6 mm/hour to 13.8 mm/hour for simvastatin. C-reactive protein (CRP) dropped from a baseline of 14.2 mg/L to 8.8 mg/L for ezetimibe, and from a baseline of 15.3 mg/L to 10.3 mg/L for simvastatin.

The patients' disease activity score also decreased somewhat, from a DAS28 of 4.41 at baseline to 3.86 for ezetimibe, and from a baseline DAS28 of 4.65 to 3.98 for simvastatin (J. Am. Coll. Cardiol. 2007;50:852-8).

Because two cholesterol-lowering agents operating by two different mechanisms each had these effects, it appears that it was the reduction in cholesterol itself that was responsible for reducing aortic stiffness and endothelial function, wrote Kaisa M. Mäki-Petäjä and her colleagues at the University of Cambridge (England).

And because the agents also reduced ESR and CRP—both markers of inflammation—as well as the rheumatoid arthritis composite DAS28, the investigators suggested that cholesterol-reducing therapies may benefit RA patients. These agents are well tolerated, improve clinical outcome in patients at risk for heart disease, and reduce surrogates of cardiovascular risk.

The investigators acknowledged, however, that future studies will be needed to establish whether reducing arterial stiffness and improving endothelial function with drugs intended to reduce hyperlipidemia will translate into an overall improvement in cardiovascular outcome in patients with RA.

The effects of simvastatin and ezetimibe differed significantly in a number of parameters. Simvastatin was better at reducing total cholesterol, LDL cholesterol, and oxidized LDL cholesterol. But they were equally effective in all other measures, including reducing inflammatory markers and aortic PWV, and increasing FMD. They were also equally effective in improving the tender-joints count and the swollen-joints count, the authors wrote.

Throughout the study, patients remained on their RA therapy, which consisted of methotrexate in 13 patients, NSAIDs in 14, prednisolone in nine, and other disease-modifying drugs in seven. In all, 18 patients took two or more drugs concomitantly and none was off RA drugs completely.

Ms. Mäki-Petäjä disclosed that her doctoral studies are funded by GlaxoSmithKline Inc., and one of the other investigators on the study disclosed receiving funding from Pfizer. Neither company is involved in marketing simvastatin or ezetimibe, both of which are manufactured by Merck & Co.

Two different cholesterol-lowering drugs reduce inflammation, disease activity, and aortic stiffness, and also improve endothelial function in patients with rheumatoid arthritis.

Participants in this randomized, double-blind crossover study included 20 patients with active rheumatoid arthritis (RA), defined as a disease activity score 28 (DAS28) greater than 3.5 and a C-reactive protein (CRP) level above 6 mg/L. None of the participants had cardiovascular disease, untreated hypertension, diabetes, elevated cholesterol, or renal disease, and none was a smoker.

Following a 2-week period during which all participants received placebo, they were given either 20 mg simvastatin or 10 mg ezetimibe for 6 weeks each, separated by a 6-week washout period before receiving the other drug for 6 weeks.

At baseline, the aortic pulse-wave velocity (PWV), a marker of aortic stiffness, was significantly higher in patients with RA than in 20 age-matched, healthy controls (9.42 m/s vs. 7.69 m/s, respectively). Likewise, flow-mediated dilatation (FMD) of the brachial artery, a marker of endothelial function, was reduced at baseline in RA patients, compared with controls. Both drugs reduced PWV while increasing FMD, but in neither case did the improvements achieve statistical significance.

Both drugs reduced total cholesterol significantly, from 5.3 mmol/L at baseline to 4.7 mmol/L for ezetimibe, and from a baseline of 5.4 mmol/L to 4.1 mmol/L for simvastatin. Likewise, both drugs reduced LDL cholesterol, from a baseline value of 3.08 mmol/L to 2.53 mmol/L for ezetimibe, and from a baseline of 3.18 mmol/L to 1.95 mmol/L for simvastatin.

Improvements—albeit less statistically significant ones—were seen in two markers of inflammation on both drugs. The erythrocyte sedimentation rate (ESR) dropped from a baseline of 18.2 mm/hour to 12.9 mm/hour for ezetimibe, and from a baseline of 18.6 mm/hour to 13.8 mm/hour for simvastatin. C-reactive protein (CRP) dropped from a baseline of 14.2 mg/L to 8.8 mg/L for ezetimibe, and from a baseline of 15.3 mg/L to 10.3 mg/L for simvastatin.

The patients' disease activity score also decreased somewhat, from a DAS28 of 4.41 at baseline to 3.86 for ezetimibe, and from a baseline DAS28 of 4.65 to 3.98 for simvastatin (J. Am. Coll. Cardiol. 2007;50:852-8).

Because two cholesterol-lowering agents operating by two different mechanisms each had these effects, it appears that it was the reduction in cholesterol itself that was responsible for reducing aortic stiffness and endothelial function, wrote Kaisa M. Mäki-Petäjä and her colleagues at the University of Cambridge (England).

And because the agents also reduced ESR and CRP—both markers of inflammation—as well as the rheumatoid arthritis composite DAS28, the investigators suggested that cholesterol-reducing therapies may benefit RA patients. These agents are well tolerated, improve clinical outcome in patients at risk for heart disease, and reduce surrogates of cardiovascular risk.

The investigators acknowledged, however, that future studies will be needed to establish whether reducing arterial stiffness and improving endothelial function with drugs intended to reduce hyperlipidemia will translate into an overall improvement in cardiovascular outcome in patients with RA.

The effects of simvastatin and ezetimibe differed significantly in a number of parameters. Simvastatin was better at reducing total cholesterol, LDL cholesterol, and oxidized LDL cholesterol. But they were equally effective in all other measures, including reducing inflammatory markers and aortic PWV, and increasing FMD. They were also equally effective in improving the tender-joints count and the swollen-joints count, the authors wrote.

Throughout the study, patients remained on their RA therapy, which consisted of methotrexate in 13 patients, NSAIDs in 14, prednisolone in nine, and other disease-modifying drugs in seven. In all, 18 patients took two or more drugs concomitantly and none was off RA drugs completely.

Ms. Mäki-Petäjä disclosed that her doctoral studies are funded by GlaxoSmithKline Inc., and one of the other investigators on the study disclosed receiving funding from Pfizer. Neither company is involved in marketing simvastatin or ezetimibe, both of which are manufactured by Merck & Co.

BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.

In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.

The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.

Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.

“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).

And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.

BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.

In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.

The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.

Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.

“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).

And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.

BARCELONA — The treatment of early rheumatoid arthritis with a combination of disease-modifying antirheumatic drugs slows radiographic progression faster in patients without antibodies against cyclic citrullinated peptide than in those patients with the antibodies, Dr. Markku Korpela said at the annual European Congress of Rheumatology.

In a subset of patients from the randomized Finnish RA Combination Therapy (FIN-RACo) trial whose anti-cyclic citrullinated peptide (CCP) status was known, 69 patients were treated initially with a drug combination that included methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone; another 60 patients were treated with sulfasalazine, with or without prednisolone.

The DMARD and prednisolone treatments were allowed to change after 2 years, according to Dr. Korpela, a rheumatologist at Tampere (Finland) University Hospital. Dr. Korpela and his colleagues found that a combination of DMARDs could significantly slow radiographic signs of RA progression (as defined by the Larsen score in hands and feet) in the absence of anti-CCP antibodies, but treatment with a single DMARD could not.

Radiographic RA progression occurred at similar rates in anti-CCP-positive and -negative patients when only one DMARD was used.

“This means that patients without CCP antibodies should be treated aggressively,” Dr. Korpela said in an interview during a poster presentation at the congress. Of the 129 patients, 92 (71%) tested positive for anti-CCP antibodies. Compared with anti-CCP-negative patients, those who tested positive for the antibodies also were significantly more likely to test positive for rheumatoid factor (83% vs. 22%) or erosive disease at baseline (54% vs. 22%).

And anti-CCP positivity predicted radiographic progression in the combination-DMARD group even when the investigators adjusted the comparison for the presence of rheumatoid factor.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

Just 25% of suspected gout patients had arthrocentesis for crystal analysis, despite the fact that the procedure remains the “gold standard” for diagnosis of the disease, according to a report by Dr. Danielle Petersel and Dr. Naomi Schlesinger.

Furthermore, of the 184 patients diagnosed with gout in one 400-bed hospital over a 2-year period from 2002 to 2004, only 38% received a rheumatology consultation, reported Dr. Petersel and Dr. Schlesinger, of the Robert Wood Johnson Medical School at New Brunswick, N.J. “The diagnostician was likely to be the admitting physician for these patients,” they wrote.

Of the 184 patients, the average age was 71 years (with a range from 40 to 96 years). All were male.

Another important finding was that a combination of anti-inflammatory agents was taken by 52% of patients, despite a lack of evidence in the literature supporting the use of combination therapy.

In fact, wrote the authors, “Combination therapy potentially puts the patient at risk of increased morbidity/mortality due to the combined effects upon the kidney.” Indeed, renal failure was present in 65% of patients with acute gout. Nevertheless, prednisone and colchicine were given in 23% of cases; nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine were given in 16%; and a steroid with an NSAID was administered in 13% of patients. Indomethacin was the most commonly prescribed NSAID (J. Rheumatol. 2007;34:1566-8).

Additionally, despite evidence that using the urate-lowering drug allopurinol to cut serum urate levels to less than 6 mg/dL is beneficial and leads to the dissolution of urate crystals and regression of tophi, only 27% were treated with the drug. “Even when it was taken, [serum urate] was not lowered to [an] SU goal of 6 mg/dL,” reported the researchers.

Rather, in 60% of patients treated with allopurinol, SU level was greater than 6 mg/dL.

“Practice patterns vary widely and support the need for education of health care professionals taking care of patients with gout,” concluded the authors.

“In our study, all patients were male, which may suggest that the cohort was somewhat biased. Long-term prospective, placebo-controlled studies are needed to establish guidelines for the diagnosis and treatment of gout,” they added.

Just 25% of suspected gout patients had arthrocentesis for crystal analysis, despite the fact that the procedure remains the “gold standard” for diagnosis of the disease, according to a report by Dr. Danielle Petersel and Dr. Naomi Schlesinger.

Furthermore, of the 184 patients diagnosed with gout in one 400-bed hospital over a 2-year period from 2002 to 2004, only 38% received a rheumatology consultation, reported Dr. Petersel and Dr. Schlesinger, of the Robert Wood Johnson Medical School at New Brunswick, N.J. “The diagnostician was likely to be the admitting physician for these patients,” they wrote.

Of the 184 patients, the average age was 71 years (with a range from 40 to 96 years). All were male.

Another important finding was that a combination of anti-inflammatory agents was taken by 52% of patients, despite a lack of evidence in the literature supporting the use of combination therapy.

In fact, wrote the authors, “Combination therapy potentially puts the patient at risk of increased morbidity/mortality due to the combined effects upon the kidney.” Indeed, renal failure was present in 65% of patients with acute gout. Nevertheless, prednisone and colchicine were given in 23% of cases; nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine were given in 16%; and a steroid with an NSAID was administered in 13% of patients. Indomethacin was the most commonly prescribed NSAID (J. Rheumatol. 2007;34:1566-8).

Additionally, despite evidence that using the urate-lowering drug allopurinol to cut serum urate levels to less than 6 mg/dL is beneficial and leads to the dissolution of urate crystals and regression of tophi, only 27% were treated with the drug. “Even when it was taken, [serum urate] was not lowered to [an] SU goal of 6 mg/dL,” reported the researchers.

Rather, in 60% of patients treated with allopurinol, SU level was greater than 6 mg/dL.

“Practice patterns vary widely and support the need for education of health care professionals taking care of patients with gout,” concluded the authors.

“In our study, all patients were male, which may suggest that the cohort was somewhat biased. Long-term prospective, placebo-controlled studies are needed to establish guidelines for the diagnosis and treatment of gout,” they added.

Just 25% of suspected gout patients had arthrocentesis for crystal analysis, despite the fact that the procedure remains the “gold standard” for diagnosis of the disease, according to a report by Dr. Danielle Petersel and Dr. Naomi Schlesinger.

Furthermore, of the 184 patients diagnosed with gout in one 400-bed hospital over a 2-year period from 2002 to 2004, only 38% received a rheumatology consultation, reported Dr. Petersel and Dr. Schlesinger, of the Robert Wood Johnson Medical School at New Brunswick, N.J. “The diagnostician was likely to be the admitting physician for these patients,” they wrote.

Of the 184 patients, the average age was 71 years (with a range from 40 to 96 years). All were male.

Another important finding was that a combination of anti-inflammatory agents was taken by 52% of patients, despite a lack of evidence in the literature supporting the use of combination therapy.

In fact, wrote the authors, “Combination therapy potentially puts the patient at risk of increased morbidity/mortality due to the combined effects upon the kidney.” Indeed, renal failure was present in 65% of patients with acute gout. Nevertheless, prednisone and colchicine were given in 23% of cases; nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine were given in 16%; and a steroid with an NSAID was administered in 13% of patients. Indomethacin was the most commonly prescribed NSAID (J. Rheumatol. 2007;34:1566-8).

Additionally, despite evidence that using the urate-lowering drug allopurinol to cut serum urate levels to less than 6 mg/dL is beneficial and leads to the dissolution of urate crystals and regression of tophi, only 27% were treated with the drug. “Even when it was taken, [serum urate] was not lowered to [an] SU goal of 6 mg/dL,” reported the researchers.

Rather, in 60% of patients treated with allopurinol, SU level was greater than 6 mg/dL.

“Practice patterns vary widely and support the need for education of health care professionals taking care of patients with gout,” concluded the authors.

“In our study, all patients were male, which may suggest that the cohort was somewhat biased. Long-term prospective, placebo-controlled studies are needed to establish guidelines for the diagnosis and treatment of gout,” they added.

Good clinical response and rheumatoid arthritis remission following treatment with tumor necrosis factor-α blockers is much rarer on the community level than results from randomized clinical trials, with their many exclusion criteria, would seem to indicate, according to results from an Italian group of researchers.

The Gruppo Italiano per lo Studio delle Early Arthritis study (GISEA) enrolled 1,257 patients who had longstanding rheumatoid arthritis (RA) and who started therapy with tumor necrosis factor-α (TNF-α) blockers. The original aim of the study was to pinpoint predictors of remission in longstanding arthritis patients treated with TNF-α blockers.

However, in the process, the researchers uncovered an unexpected finding: only 682 (54%) of patients experienced even the minimally acceptable improvement in their symptoms after 6 months of treatment with a TNF-α blocking agent. Specifically, these 682 patients were the only ones to experience at least a 0.25 improvement in their Health Assessment Questionnaire score (HAQ), which is considered the cutoff point for a clinically meaningful response.

Of the patients who dropped out, 32% cited inefficacy and 14% cited adverse events, including skin reactions, infusion reactions, and gastrointestinal problems.

Even at the outpatient clinics, only half of the patients reached a clinically meaningful result as defined by an HAQ improvement of 0.25, wrote the researchers.

“Therefore, patients in clinical practice are not representative of those recruited in clinical trials, and certainly do not reach the outcomes that have been provided in [randomized controlled clinical trials]. Among these, remission was observed in a small percentage of patients with a long disease duration,” they added.

The most likely interpretation for this discrepancy—randomized trials' extensive exclusion criteria—could “seriously influence not only the safety issue in general, but also the final clinical outcomes in aggressive and severe disease at the community level,” the study investigators noted (J. Rheumatol. 2007;34:1670-3).

Of the 682 patients who were studied further, only 591 (47% of the whole cohort) had both a 0.25 improvement in HAQ scores and underwent regular bimonthly assessments of clinical and laboratory measures.

In this cohort of 591 patients, 404 (68%) were women, and the mean age was 53 years.

Overall, 32% of the men and 24% of the women achieved remission, a difference that was statistically significant and which prompted the authors to speculate that “male patients with RA seem to benefit more from anti-TNF-α strategies than do female patients.”

Good clinical response and rheumatoid arthritis remission following treatment with tumor necrosis factor-α blockers is much rarer on the community level than results from randomized clinical trials, with their many exclusion criteria, would seem to indicate, according to results from an Italian group of researchers.

The Gruppo Italiano per lo Studio delle Early Arthritis study (GISEA) enrolled 1,257 patients who had longstanding rheumatoid arthritis (RA) and who started therapy with tumor necrosis factor-α (TNF-α) blockers. The original aim of the study was to pinpoint predictors of remission in longstanding arthritis patients treated with TNF-α blockers.

However, in the process, the researchers uncovered an unexpected finding: only 682 (54%) of patients experienced even the minimally acceptable improvement in their symptoms after 6 months of treatment with a TNF-α blocking agent. Specifically, these 682 patients were the only ones to experience at least a 0.25 improvement in their Health Assessment Questionnaire score (HAQ), which is considered the cutoff point for a clinically meaningful response.

Of the patients who dropped out, 32% cited inefficacy and 14% cited adverse events, including skin reactions, infusion reactions, and gastrointestinal problems.

Even at the outpatient clinics, only half of the patients reached a clinically meaningful result as defined by an HAQ improvement of 0.25, wrote the researchers.

“Therefore, patients in clinical practice are not representative of those recruited in clinical trials, and certainly do not reach the outcomes that have been provided in [randomized controlled clinical trials]. Among these, remission was observed in a small percentage of patients with a long disease duration,” they added.

The most likely interpretation for this discrepancy—randomized trials' extensive exclusion criteria—could “seriously influence not only the safety issue in general, but also the final clinical outcomes in aggressive and severe disease at the community level,” the study investigators noted (J. Rheumatol. 2007;34:1670-3).

Of the 682 patients who were studied further, only 591 (47% of the whole cohort) had both a 0.25 improvement in HAQ scores and underwent regular bimonthly assessments of clinical and laboratory measures.

In this cohort of 591 patients, 404 (68%) were women, and the mean age was 53 years.

Overall, 32% of the men and 24% of the women achieved remission, a difference that was statistically significant and which prompted the authors to speculate that “male patients with RA seem to benefit more from anti-TNF-α strategies than do female patients.”

Good clinical response and rheumatoid arthritis remission following treatment with tumor necrosis factor-α blockers is much rarer on the community level than results from randomized clinical trials, with their many exclusion criteria, would seem to indicate, according to results from an Italian group of researchers.

The Gruppo Italiano per lo Studio delle Early Arthritis study (GISEA) enrolled 1,257 patients who had longstanding rheumatoid arthritis (RA) and who started therapy with tumor necrosis factor-α (TNF-α) blockers. The original aim of the study was to pinpoint predictors of remission in longstanding arthritis patients treated with TNF-α blockers.

However, in the process, the researchers uncovered an unexpected finding: only 682 (54%) of patients experienced even the minimally acceptable improvement in their symptoms after 6 months of treatment with a TNF-α blocking agent. Specifically, these 682 patients were the only ones to experience at least a 0.25 improvement in their Health Assessment Questionnaire score (HAQ), which is considered the cutoff point for a clinically meaningful response.

Of the patients who dropped out, 32% cited inefficacy and 14% cited adverse events, including skin reactions, infusion reactions, and gastrointestinal problems.

Even at the outpatient clinics, only half of the patients reached a clinically meaningful result as defined by an HAQ improvement of 0.25, wrote the researchers.

“Therefore, patients in clinical practice are not representative of those recruited in clinical trials, and certainly do not reach the outcomes that have been provided in [randomized controlled clinical trials]. Among these, remission was observed in a small percentage of patients with a long disease duration,” they added.

The most likely interpretation for this discrepancy—randomized trials' extensive exclusion criteria—could “seriously influence not only the safety issue in general, but also the final clinical outcomes in aggressive and severe disease at the community level,” the study investigators noted (J. Rheumatol. 2007;34:1670-3).

Of the 682 patients who were studied further, only 591 (47% of the whole cohort) had both a 0.25 improvement in HAQ scores and underwent regular bimonthly assessments of clinical and laboratory measures.

In this cohort of 591 patients, 404 (68%) were women, and the mean age was 53 years.

Overall, 32% of the men and 24% of the women achieved remission, a difference that was statistically significant and which prompted the authors to speculate that “male patients with RA seem to benefit more from anti-TNF-α strategies than do female patients.”

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is clinically important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology. “Their [hematoxylin and eosin stains] look exactly alike,” Dr. Abbott explained.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2 positive and CK20 negative, whereas secondary EMPD is BRST 2 negative, CK20 positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7 positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the intriguing possibility that Herceptin (trastuzumab) might be an effective therapy in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is clinically important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology. “Their [hematoxylin and eosin stains] look exactly alike,” Dr. Abbott explained.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2 positive and CK20 negative, whereas secondary EMPD is BRST 2 negative, CK20 positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7 positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the intriguing possibility that Herceptin (trastuzumab) might be an effective therapy in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

AMSTERDAM — A panel of immunohistochemical stains, including human epidermal growth factor receptor 2/neu and CDX2, is useful in distinguishing extramammary Paget disease that is limited to the skin versus the subset of secondary extramammary Paget disease that is associated specifically with concurrent or future anogenital cancer, Dr. Jared Abbott said at the 11th World Congress on Cancers of the Skin.

Other investigators have postulated that the triad of cytokeratin 7 (CK7), CK20, and BRST-2 immunohistochemical stains is broadly useful in distinguishing extramammary Paget disease (EMPD) that is limited to the skin—known as primary EMPD—from all forms of secondary extramammary Paget disease, but Dr. Abbott did not find this to be the case in his own large series. Indeed, caution should be exercised in relying upon the triad of immunostains for this purpose, said Dr. Abbott of the Mayo Clinic, Rochester, Minn.

EMPD is an uncommon condition occurring primarily in the elderly, with more women than men affected. It arises as a cutaneous adenocarcinoma with a proclivity for sites rich in apocrine glands. Patients with EMPD often present with a prominent solitary plaque lesion in the anogenital or vulvar region. The lesion is erythematous, eczematous, and often pruritic. The course is often locally aggressive, with frequent recurrences.

The classic histopathologic findings of EMPD consist of clusters of epithelial cells with pagetoid extension throughout the epidermis, often accompanied by a superficial lymphocytic inflammatory infiltrate, he said at the congress, which was sponsored by the Skin Cancer Foundation and Erasmus University.

The distinction between primary and secondary EMPD is clinically important because the prognoses are entirely different. Primary EMPD, which accounts for at least three-quarters of cases, has a good prognosis, whereas secondary EMPD has a very poor prognosis because the skin disorder is often accompanied—or, in the months to come, followed—by a gastrointestinal or genitourinary malignancy. Unfortunately, primary and secondary EMPD can't be differentiated based upon histopathology. “Their [hematoxylin and eosin stains] look exactly alike,” Dr. Abbott explained.

Other investigators have turned to immunohistochemical staining patterns in an effort to make the distinction. It has been reported that primary EMPD is often CK7- and BRST-2 positive and CK20 negative, whereas secondary EMPD is BRST 2 negative, CK20 positive, and equivocal in terms of CK7.

To see if he could verify this finding, and to assess the utility of some newer immunohistochemical stains, Dr. Abbott studied excisional biopsy specimens from 61 Mayo Clinic patients with EMPD. The median age at diagnosis was 73 years, and 44 patients were women. A total of 45 patients had primary EMPD. The 16 with secondary EMPD, as determined during a median 4-year follow-up, consisted of seven patients with anorectal carcinomas, four with prostate cancer, and five with urothelial cell cancer.

All patients in both the primary and secondary EMPD groups were CK7 positive, so that was of no help, he said. In addition, CK20, BRST-2, androgen receptor, and cyclin D1 did not prove to be of much assistance in distinguishing primary from secondary EMPD. (See box.)

In contrast, HER2/neu and CDX2 were quite helpful in separating primary from secondary EMPD involving anorectal malignancy. Five of the seven patients with lower GI cancer stained positive for CDX2, and all seven were HER2/neu negative. Unfortunately, no staining pattern proved useful in identifying patients with prostate or urothelial cell cancer.

The finding that more than two-thirds of patients with primary EMPD were HER2/neu positive, and that the positivity rate was even higher among those with recurrent primary EMPD, raises the intriguing possibility that Herceptin (trastuzumab) might be an effective therapy in these individuals, although that has never been studied, Dr. Abbott said.

ELSEVIER GLOBAL MEDICAL NEWS

BIRMINGHAM, ENGLAND — Structural modification that could be achieved through mechanical, behavioral, and nutritional therapies may be a worthwhile goal in osteoarthritis treatment and a way to focus on therapy that involves more than just symptom relief, according to a presentation at the annual meeting of the British Society for Rheumatology.

A multitude of nonpharmacologic options for osteoarthritis can be pursued prior to drug treatment, Dr. Paul Dieppe said. For example, small studies support the theory that mechanically shifting the load off an affected lower-extremity joint modifies structure and alleviates symptoms of osteoarthritis.

Osteotomy, shoe wedging, and knee braces, as well as weight loss in the obese, are other options.

“If we kept thin, ate sensibly, maintained good muscle strength, avoided injuring our joints, and wore sensible shoes … there might not be as much osteoarthritis,” said Dr. Dieppe, professor of rheumatology and dean of the faculty of medicine, University of Bristol (England).

Dr. Dieppe says he is unhappy with the fact that people borrow the term “disease-modifying treatment” from the rheumatoid arthritis field and apply it to osteoarthritis.

“We go on pretending that osteoarthritis is related to rheumatoid arthritis, and just a bit different. What might disease-modifying treatment mean in osteoarthritis? We are talking about structure modification,” he said.

Structural changes can be achieved with Ilizarov frames—more commonly used by orthopedists to correct limb length discrepancies. The frames pull and increase the space between joints.

“Strangely, most of the data [so far have come] from the ankle joint,” Dr. Dieppe said. “The trials are small in numbers, but suggest very positive outcomes with recovery of the joint space in many cases, as well as symptom relief.”

Success with these frames provides proof of the concept that if the joint is unloaded, there is structure and symptom modification.

“It looks gruesome, but clearly, it can work,” Dr. Dieppe said.

Investigators should assess crepe shoes, shoe wedging, and other less invasive interventions, he added.

Osteoarthritis of the knee begins when a kinematic change occurs and shifts the load of the joint to a region unaccustomed to the new loading, according to a review article (Curr. Opin. Rheumatol. 2006;18:514–8). The authors state that the progression of osteoarthritis thereby is associated with the degree of this increased load during ambulation.

In terms of nutritional modification, trials are underway to assess any roles for vitamin C or vitamin D to slow the pathogenesis or progression of osteoarthritis, Dr. Dieppe said. Altering the course of osteoarthritis with certain dietary supplements does not work, he said, adding, “That chondroitin or glucosamine causes structural changes is a silly idea.”

“The relationship between symptom change and structural change requires further study,” he concluded.

BIRMINGHAM, ENGLAND — Structural modification that could be achieved through mechanical, behavioral, and nutritional therapies may be a worthwhile goal in osteoarthritis treatment and a way to focus on therapy that involves more than just symptom relief, according to a presentation at the annual meeting of the British Society for Rheumatology.

A multitude of nonpharmacologic options for osteoarthritis can be pursued prior to drug treatment, Dr. Paul Dieppe said. For example, small studies support the theory that mechanically shifting the load off an affected lower-extremity joint modifies structure and alleviates symptoms of osteoarthritis.

Osteotomy, shoe wedging, and knee braces, as well as weight loss in the obese, are other options.

“If we kept thin, ate sensibly, maintained good muscle strength, avoided injuring our joints, and wore sensible shoes … there might not be as much osteoarthritis,” said Dr. Dieppe, professor of rheumatology and dean of the faculty of medicine, University of Bristol (England).

Dr. Dieppe says he is unhappy with the fact that people borrow the term “disease-modifying treatment” from the rheumatoid arthritis field and apply it to osteoarthritis.

“We go on pretending that osteoarthritis is related to rheumatoid arthritis, and just a bit different. What might disease-modifying treatment mean in osteoarthritis? We are talking about structure modification,” he said.

Structural changes can be achieved with Ilizarov frames—more commonly used by orthopedists to correct limb length discrepancies. The frames pull and increase the space between joints.

“Strangely, most of the data [so far have come] from the ankle joint,” Dr. Dieppe said. “The trials are small in numbers, but suggest very positive outcomes with recovery of the joint space in many cases, as well as symptom relief.”

Success with these frames provides proof of the concept that if the joint is unloaded, there is structure and symptom modification.

“It looks gruesome, but clearly, it can work,” Dr. Dieppe said.

Investigators should assess crepe shoes, shoe wedging, and other less invasive interventions, he added.

Osteoarthritis of the knee begins when a kinematic change occurs and shifts the load of the joint to a region unaccustomed to the new loading, according to a review article (Curr. Opin. Rheumatol. 2006;18:514–8). The authors state that the progression of osteoarthritis thereby is associated with the degree of this increased load during ambulation.

In terms of nutritional modification, trials are underway to assess any roles for vitamin C or vitamin D to slow the pathogenesis or progression of osteoarthritis, Dr. Dieppe said. Altering the course of osteoarthritis with certain dietary supplements does not work, he said, adding, “That chondroitin or glucosamine causes structural changes is a silly idea.”

“The relationship between symptom change and structural change requires further study,” he concluded.

BIRMINGHAM, ENGLAND — Structural modification that could be achieved through mechanical, behavioral, and nutritional therapies may be a worthwhile goal in osteoarthritis treatment and a way to focus on therapy that involves more than just symptom relief, according to a presentation at the annual meeting of the British Society for Rheumatology.

A multitude of nonpharmacologic options for osteoarthritis can be pursued prior to drug treatment, Dr. Paul Dieppe said. For example, small studies support the theory that mechanically shifting the load off an affected lower-extremity joint modifies structure and alleviates symptoms of osteoarthritis.

Osteotomy, shoe wedging, and knee braces, as well as weight loss in the obese, are other options.

“If we kept thin, ate sensibly, maintained good muscle strength, avoided injuring our joints, and wore sensible shoes … there might not be as much osteoarthritis,” said Dr. Dieppe, professor of rheumatology and dean of the faculty of medicine, University of Bristol (England).

Dr. Dieppe says he is unhappy with the fact that people borrow the term “disease-modifying treatment” from the rheumatoid arthritis field and apply it to osteoarthritis.

“We go on pretending that osteoarthritis is related to rheumatoid arthritis, and just a bit different. What might disease-modifying treatment mean in osteoarthritis? We are talking about structure modification,” he said.

Structural changes can be achieved with Ilizarov frames—more commonly used by orthopedists to correct limb length discrepancies. The frames pull and increase the space between joints.

“Strangely, most of the data [so far have come] from the ankle joint,” Dr. Dieppe said. “The trials are small in numbers, but suggest very positive outcomes with recovery of the joint space in many cases, as well as symptom relief.”

Success with these frames provides proof of the concept that if the joint is unloaded, there is structure and symptom modification.

“It looks gruesome, but clearly, it can work,” Dr. Dieppe said.

Investigators should assess crepe shoes, shoe wedging, and other less invasive interventions, he added.

Osteoarthritis of the knee begins when a kinematic change occurs and shifts the load of the joint to a region unaccustomed to the new loading, according to a review article (Curr. Opin. Rheumatol. 2006;18:514–8). The authors state that the progression of osteoarthritis thereby is associated with the degree of this increased load during ambulation.

In terms of nutritional modification, trials are underway to assess any roles for vitamin C or vitamin D to slow the pathogenesis or progression of osteoarthritis, Dr. Dieppe said. Altering the course of osteoarthritis with certain dietary supplements does not work, he said, adding, “That chondroitin or glucosamine causes structural changes is a silly idea.”

“The relationship between symptom change and structural change requires further study,” he concluded.

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

Patients who take hydroxychloroquine for their rheumatoid arthritis symptoms also show a dose-dependent reduction in their risk for developing diabetes, results of a large study suggest.

Diabetes risk decreased by as much as 77% in patients who took the antimalarial drug hydroxychloroquine for more than 4 years, “a finding that is comparable or superior to that of other drugs studied in clinical trials: rosiglitazone, combination hormone therapy, estrogen [only], metformin, acarbose, and ramipril,” the study researchers reported.

This is the first evidence that has ever been reported suggesting that hydroxychloroquine reduces the risk of diabetes in RA patients, wrote Dr. Mary Chester M. Wasko, of the University of Pittsburgh, and her associates.

Antimalarials are known to cause hypoglycemia and are thought to improve insulin secretion and peripheral insulin sensitivity. They “have been explored as an adjunct to insulin and oral hypoglycemic agents for poorly controlled type 2 diabetes,” Dr. Wasko and her associates said.

The investigators studied the possible link between use of hydroxychloroquine and diabetes risk in an established RA cohort with more than 20 years of follow-up.

The 4,905 subjects in this longitudinal observational study were treated at seven RA practice sites across North America from 1976 through 2004. A total of 1,808 reported use of hydroxychloroquine at some time during the study, most of them for an average of 3 years.

Diabetes developed in 70% of the subjects who had never taken the antimalarial drug, compared with only 48% of those who had ever taken it.

Diabetes incidence rates were 8.9 per 1,000 patient-years of observation among those who had never before taken hydroxychloroquine, compared with 5.2 per 1,000 patient-years for those who had taken the drug.

In addition, “the relative risk of developing diabetes progressively declined with increasing time taking hydroxychloroquine,” the investigators said (JAMA 2007;298:187–93).

Patients who did develop diabetes after taking the antimalarial were less likely than were those who hadn't taken it to need oral hypoglycemic medication.

“Hydroxychloroquine use may modify the clinical manifestations of hyperglycemia, or it may attenuate hyperglycemia and reduce the need for medications once this diagnosis is established,” Dr. Wasko and her associates commented.

Although antimalarials do not address RA signs and symptoms as well as other current treatment options, their toxicity profile is better, so they are used for mild to moderate disease and in combination therapy.

Unlike the traditional RA medications, antimalarials are well tolerated, do not require routine laboratory monitoring for toxicity, confer no increased risk of infection or malignancy, and carry “minimal” risk for adversely affecting internal organs when dosing is tailored to body weight, the researchers said.

Even though this study involved only RA patients, the results also may apply to people who do not have RA, because hydroxychloroquine may prove beneficial in preventing diabetes in high-risk members of the general population, the researchers added.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

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BARCELONA — Rheumatoid arthritis patients who use corticosteroids frequently over the long term can maintain a low disease activity state but suffer deterioration of their functional capability, Dr. Eiichi Tanaka reported at a poster session at the annual European Congress of Rheumatology.

“A low disease activity state caused by corticosteroid use may not represent a 'true' low disease activity state,” explained Dr. Tanaka of Tokyo Women's Medical University, and his associates.

The investigators followed 224 RA patients with a low disease activity state during 2000–2005. The patients had a mean age of 56 years and a mean disease duration of about 8 years, and were enrolled in the study for at least 3 years. Every 6 months, the investigators collected measurements on the Disease Activity Score-28 (DAS-28) and Japanese version of the Health Assessment Questionnaire (J-HAQ).

DAS-28 scores did not change substantially over the course of the study in 135 patients who never used corticosteroids, 33 who used steroids an average of less than 9 months per year, and 56 who took steroids an average of more than 9 months per year. None of the patients had a DAS-28 greater than 3.2 at each assessment.

But long-term functional capacity, as measured by the J-HAQ, declined in the heavy corticosteroid users, improved slightly among moderate corticosteroid users, and improved the most in patients who did not use corticosteroids. Corticosteroid use was the most significant factor contributing to the final J-HAQ score, after adjustment of a multiple linear regression analysis for age, gender, disease duration, initial J-HAQ score, and seasonal effects. A little more than 90% of the patients in each group used disease-modifying antirheumatic drugs during the study.

“Along with the achievement of a low disease activity state, long-term efficacy, long-term functional prognosis, and the quality of remission also need to be considered in the strict control of RA activity,” Dr. Tanaka and his colleagues concluded.

BARCELONA — Rheumatoid arthritis patients who use corticosteroids frequently over the long term can maintain a low disease activity state but suffer deterioration of their functional capability, Dr. Eiichi Tanaka reported at a poster session at the annual European Congress of Rheumatology.

“A low disease activity state caused by corticosteroid use may not represent a 'true' low disease activity state,” explained Dr. Tanaka of Tokyo Women's Medical University, and his associates.

The investigators followed 224 RA patients with a low disease activity state during 2000–2005. The patients had a mean age of 56 years and a mean disease duration of about 8 years, and were enrolled in the study for at least 3 years. Every 6 months, the investigators collected measurements on the Disease Activity Score-28 (DAS-28) and Japanese version of the Health Assessment Questionnaire (J-HAQ).

DAS-28 scores did not change substantially over the course of the study in 135 patients who never used corticosteroids, 33 who used steroids an average of less than 9 months per year, and 56 who took steroids an average of more than 9 months per year. None of the patients had a DAS-28 greater than 3.2 at each assessment.

But long-term functional capacity, as measured by the J-HAQ, declined in the heavy corticosteroid users, improved slightly among moderate corticosteroid users, and improved the most in patients who did not use corticosteroids. Corticosteroid use was the most significant factor contributing to the final J-HAQ score, after adjustment of a multiple linear regression analysis for age, gender, disease duration, initial J-HAQ score, and seasonal effects. A little more than 90% of the patients in each group used disease-modifying antirheumatic drugs during the study.

“Along with the achievement of a low disease activity state, long-term efficacy, long-term functional prognosis, and the quality of remission also need to be considered in the strict control of RA activity,” Dr. Tanaka and his colleagues concluded.

BARCELONA — Rheumatoid arthritis patients who use corticosteroids frequently over the long term can maintain a low disease activity state but suffer deterioration of their functional capability, Dr. Eiichi Tanaka reported at a poster session at the annual European Congress of Rheumatology.

“A low disease activity state caused by corticosteroid use may not represent a 'true' low disease activity state,” explained Dr. Tanaka of Tokyo Women's Medical University, and his associates.

The investigators followed 224 RA patients with a low disease activity state during 2000–2005. The patients had a mean age of 56 years and a mean disease duration of about 8 years, and were enrolled in the study for at least 3 years. Every 6 months, the investigators collected measurements on the Disease Activity Score-28 (DAS-28) and Japanese version of the Health Assessment Questionnaire (J-HAQ).

DAS-28 scores did not change substantially over the course of the study in 135 patients who never used corticosteroids, 33 who used steroids an average of less than 9 months per year, and 56 who took steroids an average of more than 9 months per year. None of the patients had a DAS-28 greater than 3.2 at each assessment.

But long-term functional capacity, as measured by the J-HAQ, declined in the heavy corticosteroid users, improved slightly among moderate corticosteroid users, and improved the most in patients who did not use corticosteroids. Corticosteroid use was the most significant factor contributing to the final J-HAQ score, after adjustment of a multiple linear regression analysis for age, gender, disease duration, initial J-HAQ score, and seasonal effects. A little more than 90% of the patients in each group used disease-modifying antirheumatic drugs during the study.

“Along with the achievement of a low disease activity state, long-term efficacy, long-term functional prognosis, and the quality of remission also need to be considered in the strict control of RA activity,” Dr. Tanaka and his colleagues concluded.