Osteoarthritis

In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.

But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.

Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.

Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.

The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).

At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).

The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.

The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.

In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.

But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.

Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.

Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.

The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).

At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).

The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.

The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.

In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.

But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.

Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.

Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.

The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).

At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).

The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.

The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.

Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.

From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.

© Jupiterimages/Getty Images

The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.

Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.

This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).

The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.

This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.

Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.

From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.

© Jupiterimages/Getty Images

The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.

Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.

This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).

The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.

This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.

Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.

From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.

© Jupiterimages/Getty Images

The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.

Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.

This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).

The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.

This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."

Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).

The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.

Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.

In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).

The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.

This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.

SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.

"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.

Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.

The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).

The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).

Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.

In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).

Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.

Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.

"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.

Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.

The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).

The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).

Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.

In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).

Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.

Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.

"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.

Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.

The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).

The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).

Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.

In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).

Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.

Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.

bjancin@frontlinemedcom.com

Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.

Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).

The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)

After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.

The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.

The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.

Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.

There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.

No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.

"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.

They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.

The authors reported no relevant financial disclosures.

jevans@frontlinemedcom.com

Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.

Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).

The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)

After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.

The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.

The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.

Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.

There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.

No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.

"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.

They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.

The authors reported no relevant financial disclosures.

jevans@frontlinemedcom.com

Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.

Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).

The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)

After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.

The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.

The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.

Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.

There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.

No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.

"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.

They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.

The authors reported no relevant financial disclosures.

jevans@frontlinemedcom.com

New knee osteoarthritis guidelines from Osteoarthritis Research Society International, an update of the group’s 2010 guidelines, recommend weight loss, education, exercise, and much more that’s familiar to practicing rheumatologists.

However, the group’s advice varies a bit from recent osteoarthritis (OA) guidelines separately issued by the American College of Rheumatology (ACR) and the American Academy of Orthopaedic Surgeons (AAOS).

For instance, the AAOS was neutral on acetaminophen and corticosteroid knee shots in its 2013 recommendations, citing a lack of evidence, but Osteoarthritis Research Society International (OARSI) guidelines recommend both in the absence of relevant comorbidities. Recent studies of steroid knee shots demonstrate "clinically significant short-term decreases in pain" that are "significantly greater" than are those with intra-articular hyaluronic acid, according to guidelines lead author Dr. Timothy McAlindon, chief of rheumatology at Tufts University in Boston, and his colleagues (Osteoarthritis Cartilage 2014 Jan. 23 [doi:10.1016/j.joca.2014.01.003]).

Meanwhile, hyaluronic acid knee injections provided greater long-term relief in another study, one of the findings that led OARSI, like the ACR, to suggest that the jury’s still out on hyaluronic acid. The AAOS rejected hyaluronic acid because of a lack of efficacy.

OARSI’s advice is based on recent literature and the expert opinion of its 13-member review panel; most members were rheumatologists and most were European. They voted on 13 nonpharmaceutical and 16 pharmaceutical treatments, deciding if they were appropriate, inappropriate, or – when evidence was scanty – of uncertain value for knee OA.

Treatments that made the cut as appropriate for all knee OA patients included biomechanical interventions, corticosteroid knee injections, land and water-based exercise, self-management and education, strength training, and weight management. Other treatments approved by the panelists included acetaminophen, warm soaks in mineral-rich water (balneotherapy), topical capsaicin, walking canes, duloxetine (Cymbalta), and NSAIDs when comorbidities don’t rule them out.

A variety of therapies fell into the "uncertain" category: acupuncture, avocado-soybean unsaponfiable supplements, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids, rose hip, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. The group voted risedronate (Actonel) and neuromuscular electrical stimulation as inappropriate for knee OA because of a lack of evidence.

Newer findings have "increased safety concerns regarding use of treatments such as acetaminophen and opioids ... while evidence for use of treatments such as duloxetine, balneotherapy, and land-based exercises such as t’ai chi has strengthened," the authors noted.

OARSI reviewed biomechanical interventions more favorably than did the other groups, mostly because research now suggests that knee braces and foot orthoses improve function and decrease pain, stiffness, and drug use. Another trial supported wedged insoles as an alternative to valgus bracing.

Similar to the ACR guidelines but unlike stronger recommendations from the AAOS, OARSI also supported oral NSAIDs for most patients but was unsure about them when patients have heart disease and other relevant problems. The group recommended concomitant proton-pump inhibitors when gastric bleeding is a worry.

They noted that naproxen seems safer on the cardiovascular system than COX-2 inhibitors. Diclofenac appears to carry the highest risk for abnormal liver values, while celecoxib (Celebrex) seems to cause fewer ulcers but more cardiovascular problems. Topical NSAIDs work as well as oral formulations for OA knee pain, with fewer problems.

Unlike the ACR, the group also considered topical capsaicin "appropriate in patients without relevant comorbidities" and duloxetine "appropriate for most clinical subphenotypes," although adverse events – nausea, fatigue, and others – and the "availability of more targeted therapies predicated uncertain appropriateness for individuals with knee-only OA and comorbidities," they said.

OARSI funded the work, and is supported by companies promoting arthritis products. Most of the panelists have financial ties to Sanofi, Pfizer, Merck, Don-Joy, and other companies, but recused themselves when needed from voting.

aotto@frontlinemedcom.com

New knee osteoarthritis guidelines from Osteoarthritis Research Society International, an update of the group’s 2010 guidelines, recommend weight loss, education, exercise, and much more that’s familiar to practicing rheumatologists.

However, the group’s advice varies a bit from recent osteoarthritis (OA) guidelines separately issued by the American College of Rheumatology (ACR) and the American Academy of Orthopaedic Surgeons (AAOS).

For instance, the AAOS was neutral on acetaminophen and corticosteroid knee shots in its 2013 recommendations, citing a lack of evidence, but Osteoarthritis Research Society International (OARSI) guidelines recommend both in the absence of relevant comorbidities. Recent studies of steroid knee shots demonstrate "clinically significant short-term decreases in pain" that are "significantly greater" than are those with intra-articular hyaluronic acid, according to guidelines lead author Dr. Timothy McAlindon, chief of rheumatology at Tufts University in Boston, and his colleagues (Osteoarthritis Cartilage 2014 Jan. 23 [doi:10.1016/j.joca.2014.01.003]).

Meanwhile, hyaluronic acid knee injections provided greater long-term relief in another study, one of the findings that led OARSI, like the ACR, to suggest that the jury’s still out on hyaluronic acid. The AAOS rejected hyaluronic acid because of a lack of efficacy.

OARSI’s advice is based on recent literature and the expert opinion of its 13-member review panel; most members were rheumatologists and most were European. They voted on 13 nonpharmaceutical and 16 pharmaceutical treatments, deciding if they were appropriate, inappropriate, or – when evidence was scanty – of uncertain value for knee OA.

Treatments that made the cut as appropriate for all knee OA patients included biomechanical interventions, corticosteroid knee injections, land and water-based exercise, self-management and education, strength training, and weight management. Other treatments approved by the panelists included acetaminophen, warm soaks in mineral-rich water (balneotherapy), topical capsaicin, walking canes, duloxetine (Cymbalta), and NSAIDs when comorbidities don’t rule them out.

A variety of therapies fell into the "uncertain" category: acupuncture, avocado-soybean unsaponfiable supplements, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids, rose hip, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. The group voted risedronate (Actonel) and neuromuscular electrical stimulation as inappropriate for knee OA because of a lack of evidence.

Newer findings have "increased safety concerns regarding use of treatments such as acetaminophen and opioids ... while evidence for use of treatments such as duloxetine, balneotherapy, and land-based exercises such as t’ai chi has strengthened," the authors noted.

OARSI reviewed biomechanical interventions more favorably than did the other groups, mostly because research now suggests that knee braces and foot orthoses improve function and decrease pain, stiffness, and drug use. Another trial supported wedged insoles as an alternative to valgus bracing.

Similar to the ACR guidelines but unlike stronger recommendations from the AAOS, OARSI also supported oral NSAIDs for most patients but was unsure about them when patients have heart disease and other relevant problems. The group recommended concomitant proton-pump inhibitors when gastric bleeding is a worry.

They noted that naproxen seems safer on the cardiovascular system than COX-2 inhibitors. Diclofenac appears to carry the highest risk for abnormal liver values, while celecoxib (Celebrex) seems to cause fewer ulcers but more cardiovascular problems. Topical NSAIDs work as well as oral formulations for OA knee pain, with fewer problems.

Unlike the ACR, the group also considered topical capsaicin "appropriate in patients without relevant comorbidities" and duloxetine "appropriate for most clinical subphenotypes," although adverse events – nausea, fatigue, and others – and the "availability of more targeted therapies predicated uncertain appropriateness for individuals with knee-only OA and comorbidities," they said.

OARSI funded the work, and is supported by companies promoting arthritis products. Most of the panelists have financial ties to Sanofi, Pfizer, Merck, Don-Joy, and other companies, but recused themselves when needed from voting.

aotto@frontlinemedcom.com

New knee osteoarthritis guidelines from Osteoarthritis Research Society International, an update of the group’s 2010 guidelines, recommend weight loss, education, exercise, and much more that’s familiar to practicing rheumatologists.

However, the group’s advice varies a bit from recent osteoarthritis (OA) guidelines separately issued by the American College of Rheumatology (ACR) and the American Academy of Orthopaedic Surgeons (AAOS).

For instance, the AAOS was neutral on acetaminophen and corticosteroid knee shots in its 2013 recommendations, citing a lack of evidence, but Osteoarthritis Research Society International (OARSI) guidelines recommend both in the absence of relevant comorbidities. Recent studies of steroid knee shots demonstrate "clinically significant short-term decreases in pain" that are "significantly greater" than are those with intra-articular hyaluronic acid, according to guidelines lead author Dr. Timothy McAlindon, chief of rheumatology at Tufts University in Boston, and his colleagues (Osteoarthritis Cartilage 2014 Jan. 23 [doi:10.1016/j.joca.2014.01.003]).

Meanwhile, hyaluronic acid knee injections provided greater long-term relief in another study, one of the findings that led OARSI, like the ACR, to suggest that the jury’s still out on hyaluronic acid. The AAOS rejected hyaluronic acid because of a lack of efficacy.

OARSI’s advice is based on recent literature and the expert opinion of its 13-member review panel; most members were rheumatologists and most were European. They voted on 13 nonpharmaceutical and 16 pharmaceutical treatments, deciding if they were appropriate, inappropriate, or – when evidence was scanty – of uncertain value for knee OA.

Treatments that made the cut as appropriate for all knee OA patients included biomechanical interventions, corticosteroid knee injections, land and water-based exercise, self-management and education, strength training, and weight management. Other treatments approved by the panelists included acetaminophen, warm soaks in mineral-rich water (balneotherapy), topical capsaicin, walking canes, duloxetine (Cymbalta), and NSAIDs when comorbidities don’t rule them out.

A variety of therapies fell into the "uncertain" category: acupuncture, avocado-soybean unsaponfiable supplements, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids, rose hip, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. The group voted risedronate (Actonel) and neuromuscular electrical stimulation as inappropriate for knee OA because of a lack of evidence.

Newer findings have "increased safety concerns regarding use of treatments such as acetaminophen and opioids ... while evidence for use of treatments such as duloxetine, balneotherapy, and land-based exercises such as t’ai chi has strengthened," the authors noted.

OARSI reviewed biomechanical interventions more favorably than did the other groups, mostly because research now suggests that knee braces and foot orthoses improve function and decrease pain, stiffness, and drug use. Another trial supported wedged insoles as an alternative to valgus bracing.

Similar to the ACR guidelines but unlike stronger recommendations from the AAOS, OARSI also supported oral NSAIDs for most patients but was unsure about them when patients have heart disease and other relevant problems. The group recommended concomitant proton-pump inhibitors when gastric bleeding is a worry.

They noted that naproxen seems safer on the cardiovascular system than COX-2 inhibitors. Diclofenac appears to carry the highest risk for abnormal liver values, while celecoxib (Celebrex) seems to cause fewer ulcers but more cardiovascular problems. Topical NSAIDs work as well as oral formulations for OA knee pain, with fewer problems.

Unlike the ACR, the group also considered topical capsaicin "appropriate in patients without relevant comorbidities" and duloxetine "appropriate for most clinical subphenotypes," although adverse events – nausea, fatigue, and others – and the "availability of more targeted therapies predicated uncertain appropriateness for individuals with knee-only OA and comorbidities," they said.

OARSI funded the work, and is supported by companies promoting arthritis products. Most of the panelists have financial ties to Sanofi, Pfizer, Merck, Don-Joy, and other companies, but recused themselves when needed from voting.

aotto@frontlinemedcom.com

SAN DIEGO – Patients with osteoarthritis of the knee who wore a patellofemoral brace for 6 weeks experienced a significant reduction in pain and in bone marrow lesion volumes in the patellofemoral region, compared with those who did not wear the brace, a multicenter trial showed.

"There’s a pressing need for nonsurgical intervention for knee osteoarthritis," Dr. David T. Felson said in a press briefing at the annual meeting of the American College of Rheumatology.

"There are no currently approved structure-modifying treatments. This has been a focus of studies that have been testing modifying treatments on hyaline cartilage, which changes slowly, necessitating expensive, long-term, large trials. Even so, mechanopathology such as that caused by malalignment or meniscal tears may make it impossible to protect cartilage in existing OA," he noted.

Dr. Felson, director of the Research in Osteoarthritis in Manchester group at the University of Manchester (England) and professor of medicine at Boston University, went on to note that bone marrow lesions (BMLs) "have been well shown to predict later cartilage loss in that location and correlate with pain and its severity. Recently, we showed that BMLs fluctuate in volume in as little as 6 weeks. Further, one small trial has suggested that zoledronic acid may shrink BMLs and reduce knee pain. That leads us to suggest that BMLs may be a viable treatment target in OA."

The patellofemoral joint "is a major source of knee pain in OA, and there has been little study of the efficacy of PF braces," he continued. "In a body mechanics study, PF bracing has been shown to increase the contact area of the PF joint. It may thereby lower the contact stress and shrink BMLs."

He and his associates set out to determine whether bracing would improve pain and lessen the volume of BMLs in patients with knee OA. They enrolled 126 patients with a mean age of 55 years whose knee pain had been present daily for the previous 3 months. Half of the patients wore a soft neoprene PF brace for a mean of 7.3 hours per day, while the other half did not.

All study participants "had to have at least a score of 40 on a 0-100 mm visual analogue scale (VAS) for nominated aggravating activity likely to originate in the PF joint," Dr. Felson said. "They had to have pain with activities such as stair climbing, kneeling, prolonged sitting or squatting, [and] they also had to have a radiographic KL [Kellgren-Lawrence] score of grade 2 or 3 in the PF joint. That score had to be greater than the KL score for the tibiofemoral compartments. They also had to undergo a clinical exam by a trained physiotherapist to confirm PF joint tenderness."

The researchers performed contrast-enhanced knee MRIs at baseline and at 6 weeks. The primary symptom outcome measure was VAS pain during the patients’ nominated aggravating activity, while the primary structural outcome measure was BML volume in the PF joint as assessed on sagittal precontrast view.

At 6 weeks, Dr. Felson reported that patients in the no-brace group had a mean reduction in their VAS pain of 1.3, compared with a reduction of 18.2 in the braced group, a mean between-group difference of 16.9 that reached statistical significance (P less than .001).

As for PF BML volume, patients in the no-brace group showed a slight increase in volume (mean, 102.7 mm³), while the braced group showed a significant decrease in PF BML volume (mean, –554.9 mm³), for a mean between-group difference of 657.6 mm³ that reached statistical significance (P = .02). "That represents about a 25% decrease in volume," Dr. Felson said.

No differences were observed between the two groups in terms of tibiofemoral BML volume or in synovitis volume.

Dr. Felson acknowledged certain limitations of the study, including its 6-week design. "OA is a long-term chronic disease," he said. "We don’t know what relevance our findings have for longer-term structure changes of the knee."

The researchers stated that they had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Patients with osteoarthritis of the knee who wore a patellofemoral brace for 6 weeks experienced a significant reduction in pain and in bone marrow lesion volumes in the patellofemoral region, compared with those who did not wear the brace, a multicenter trial showed.

"There’s a pressing need for nonsurgical intervention for knee osteoarthritis," Dr. David T. Felson said in a press briefing at the annual meeting of the American College of Rheumatology.

"There are no currently approved structure-modifying treatments. This has been a focus of studies that have been testing modifying treatments on hyaline cartilage, which changes slowly, necessitating expensive, long-term, large trials. Even so, mechanopathology such as that caused by malalignment or meniscal tears may make it impossible to protect cartilage in existing OA," he noted.

Dr. Felson, director of the Research in Osteoarthritis in Manchester group at the University of Manchester (England) and professor of medicine at Boston University, went on to note that bone marrow lesions (BMLs) "have been well shown to predict later cartilage loss in that location and correlate with pain and its severity. Recently, we showed that BMLs fluctuate in volume in as little as 6 weeks. Further, one small trial has suggested that zoledronic acid may shrink BMLs and reduce knee pain. That leads us to suggest that BMLs may be a viable treatment target in OA."

The patellofemoral joint "is a major source of knee pain in OA, and there has been little study of the efficacy of PF braces," he continued. "In a body mechanics study, PF bracing has been shown to increase the contact area of the PF joint. It may thereby lower the contact stress and shrink BMLs."

He and his associates set out to determine whether bracing would improve pain and lessen the volume of BMLs in patients with knee OA. They enrolled 126 patients with a mean age of 55 years whose knee pain had been present daily for the previous 3 months. Half of the patients wore a soft neoprene PF brace for a mean of 7.3 hours per day, while the other half did not.

All study participants "had to have at least a score of 40 on a 0-100 mm visual analogue scale (VAS) for nominated aggravating activity likely to originate in the PF joint," Dr. Felson said. "They had to have pain with activities such as stair climbing, kneeling, prolonged sitting or squatting, [and] they also had to have a radiographic KL [Kellgren-Lawrence] score of grade 2 or 3 in the PF joint. That score had to be greater than the KL score for the tibiofemoral compartments. They also had to undergo a clinical exam by a trained physiotherapist to confirm PF joint tenderness."

The researchers performed contrast-enhanced knee MRIs at baseline and at 6 weeks. The primary symptom outcome measure was VAS pain during the patients’ nominated aggravating activity, while the primary structural outcome measure was BML volume in the PF joint as assessed on sagittal precontrast view.

At 6 weeks, Dr. Felson reported that patients in the no-brace group had a mean reduction in their VAS pain of 1.3, compared with a reduction of 18.2 in the braced group, a mean between-group difference of 16.9 that reached statistical significance (P less than .001).

As for PF BML volume, patients in the no-brace group showed a slight increase in volume (mean, 102.7 mm³), while the braced group showed a significant decrease in PF BML volume (mean, –554.9 mm³), for a mean between-group difference of 657.6 mm³ that reached statistical significance (P = .02). "That represents about a 25% decrease in volume," Dr. Felson said.

No differences were observed between the two groups in terms of tibiofemoral BML volume or in synovitis volume.

Dr. Felson acknowledged certain limitations of the study, including its 6-week design. "OA is a long-term chronic disease," he said. "We don’t know what relevance our findings have for longer-term structure changes of the knee."

The researchers stated that they had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Patients with osteoarthritis of the knee who wore a patellofemoral brace for 6 weeks experienced a significant reduction in pain and in bone marrow lesion volumes in the patellofemoral region, compared with those who did not wear the brace, a multicenter trial showed.

"There’s a pressing need for nonsurgical intervention for knee osteoarthritis," Dr. David T. Felson said in a press briefing at the annual meeting of the American College of Rheumatology.

"There are no currently approved structure-modifying treatments. This has been a focus of studies that have been testing modifying treatments on hyaline cartilage, which changes slowly, necessitating expensive, long-term, large trials. Even so, mechanopathology such as that caused by malalignment or meniscal tears may make it impossible to protect cartilage in existing OA," he noted.

Dr. Felson, director of the Research in Osteoarthritis in Manchester group at the University of Manchester (England) and professor of medicine at Boston University, went on to note that bone marrow lesions (BMLs) "have been well shown to predict later cartilage loss in that location and correlate with pain and its severity. Recently, we showed that BMLs fluctuate in volume in as little as 6 weeks. Further, one small trial has suggested that zoledronic acid may shrink BMLs and reduce knee pain. That leads us to suggest that BMLs may be a viable treatment target in OA."

The patellofemoral joint "is a major source of knee pain in OA, and there has been little study of the efficacy of PF braces," he continued. "In a body mechanics study, PF bracing has been shown to increase the contact area of the PF joint. It may thereby lower the contact stress and shrink BMLs."

He and his associates set out to determine whether bracing would improve pain and lessen the volume of BMLs in patients with knee OA. They enrolled 126 patients with a mean age of 55 years whose knee pain had been present daily for the previous 3 months. Half of the patients wore a soft neoprene PF brace for a mean of 7.3 hours per day, while the other half did not.

All study participants "had to have at least a score of 40 on a 0-100 mm visual analogue scale (VAS) for nominated aggravating activity likely to originate in the PF joint," Dr. Felson said. "They had to have pain with activities such as stair climbing, kneeling, prolonged sitting or squatting, [and] they also had to have a radiographic KL [Kellgren-Lawrence] score of grade 2 or 3 in the PF joint. That score had to be greater than the KL score for the tibiofemoral compartments. They also had to undergo a clinical exam by a trained physiotherapist to confirm PF joint tenderness."

The researchers performed contrast-enhanced knee MRIs at baseline and at 6 weeks. The primary symptom outcome measure was VAS pain during the patients’ nominated aggravating activity, while the primary structural outcome measure was BML volume in the PF joint as assessed on sagittal precontrast view.

At 6 weeks, Dr. Felson reported that patients in the no-brace group had a mean reduction in their VAS pain of 1.3, compared with a reduction of 18.2 in the braced group, a mean between-group difference of 16.9 that reached statistical significance (P less than .001).

As for PF BML volume, patients in the no-brace group showed a slight increase in volume (mean, 102.7 mm³), while the braced group showed a significant decrease in PF BML volume (mean, –554.9 mm³), for a mean between-group difference of 657.6 mm³ that reached statistical significance (P = .02). "That represents about a 25% decrease in volume," Dr. Felson said.

No differences were observed between the two groups in terms of tibiofemoral BML volume or in synovitis volume.

Dr. Felson acknowledged certain limitations of the study, including its 6-week design. "OA is a long-term chronic disease," he said. "We don’t know what relevance our findings have for longer-term structure changes of the knee."

The researchers stated that they had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.

The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.

Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.

The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.

That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.

Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.

Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.

The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.

The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.

Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.

The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.

That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.

Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.

Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.

The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Viscosupplementation using hyaluronic acid injections delayed total knee replacement for patients with knee osteoarthritis by up to a median 2.6 years in a retrospective observational study.

The study, involving analysis of a large commercial health insurance claims database (Truven MarketScan), included all 16,529 patients with knee osteoarthritis (OA) who made their first visit to a specialist for the condition in 2008-2011 and who eventually went on to total knee replacement surgery.

Among this group were 4,178 knee OA patients who underwent one or more courses of treatment with any of the Food and Drug Administration–approved injectable hyaluronic acid products. A total of 3,647 of these patients were successfully matched to controls with knee OA who had total knee replacement surgery without any prior hyaluronic acid injections, Dr. Roy D. Altman explained at the annual meeting of the American College of Rheumatology.

The matching process relied upon propensity scores based on age, sex, physician specialty, diagnosis at the first specialist visit, and year. Therein lays a significant study limitation: These variables provide only limited ability to adjust for any differences in baseline knee OA severity that might have existed between patients who did or didn’t receive hyaluronic acid injections. Nor can an observational study establish causality, observed Dr. Altman, professor emeritus of medicine at the University of California, Los Angeles.

That being said, the study demonstrated a strong dose-dependent relationship between viscosupplementation and time from first specialist visit to knee replacement surgery, he noted.

Seventy-nine percent of patients who got hyaluronic acid injections received a single course consisting of either one injection or a series of injections, depending upon the specific product. Those patients experienced a median 233-day increase in the time to surgery, compared with matched controls who didn’t get hyaluronic acid injections.

Moreover, the 16% of viscosupplementation recipients who underwent a second round of treatment further delayed their median time from first specialist visit to total knee replacement by an additional 7 months. And that pattern continued in the relatively small numbers of patients who underwent three or more courses of viscosupplementation: Each round of hyaluronic acid injections brought a roughly 7-month further delay in time to surgery, out to a total of 2.6 years.

The study was sponsored by Johnson & Johnson. Dr. Altman reported having no financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.

That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.

The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.

The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.

"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.

In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.

ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.

All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.

The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.

This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.

That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.

The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.

The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.

"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.

In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.

ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.

All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.

The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.

This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Knee osteoarthritis is too frequently underdiagnosed and undertreated by primary care physicians and bariatric surgeons in obese patients considering weight loss surgery.

That’s the conclusion Dr. Janice Lin and her coinvestigators at New York University reached based upon their prospective study in which 408 consecutive patients scheduled for bariatric surgery at NYU Langone Medical Center and Bellevue Hospital were screened for this common form of arthritis.

The researchers found that 54% of the obese patients reported significant knee pain. Of these 221 patients, 26 weren’t interested in further evaluation, but 115 were deemed likely to have knee osteoarthritis (OA) on the basis of a brief screen indicating they had knee pain on more than 15 days per month for longer than 1 month, had a visual analog scale (VAS) pain score of at least 30 out of 100, and didn’t have lupus, bilateral knee replacement, crystal disease, psoriasis, or an inflammatory arthritis. These 115 patients formed the study population for this ongoing prospective investigation.

The primary care physicians of only 47% of these 115 patients had evaluated their knee pain. Bariatric surgeons had similarly not addressed the knee pain in about half of cases. Indeed, fewer than one-third of these obese patients with knee pain had been assessed via knee x-rays in accord with guideline-recommended practice.

"In the bariatric population, knee pain is often attributed to mechanical load from obesity without proper evaluation or treatment. Patients are rarely referred to rheumatologists or other appropriate specialists, though they may benefit from such evaluation and management," according to Dr. Lin.

In fact, only 3% of these patients with significant knee pain had been referred to a rheumatologist and 15% to an orthopedic surgeon.

ACR treatment guidelines were for the most part not being followed. Although roughly three-quarters of patients were taking NSAIDs and/or acetaminophen, only 31% of the group had been referred for physical therapy, 14% had received a steroid injection, 11% used a topical NSAID, and 1% had undergone viscosupplementation, recommended as a second-line therapy.

All 115 study participants got a baseline posterior-anterior standing bilateral knee x-ray scored for Kellgren-Lawrence grade. Based on the findings, 19% of patients were determined to not have knee OA, 21% had mild Kellgren-Lawrence grade 1 disease, and the rest had more advanced knee OA.

The group’s mean baseline VAS pain score was 64.5. Their Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) mean pain, stiffness, and function scores were 268, 102, and 938, respectively.

This ongoing study builds upon an earlier retrospective study by Dr. Lin’s coinvestigators at New York University, who reported that 51% of 192 patients who underwent bariatric laparoscopic banding surgery had complete improvement in knee OA pain 19 months later.In the ongoing prospective study, participants will repeat the WOMAC and other validated measures of knee OA pain and function 1, 3, and 6 months after laparascopic banding, sleeve gastrectomy, or gastric bypass. They will also have follow-up knee x-rays. Dr. Lin and her coworkers will be eager to see if any of the three types of bariatric surgery is advantageous in terms of its impact on knee pain, she said.

She reported having no relevant financial conflicts.

bjancin@frontlinemedcom.com

SAN DIEGO – Osteoarthritis patients who meet federal guidelines for exercise have more days of perfect health per year than do their sedentary counterparts, results from a novel study suggest.

"Our findings support interventions that help older adults to increase their physical activity level, even if guidelines are not fully met," Dr. Kai Sun said during a press briefing at the annual meeting of the American College of Rheumatology. "Increased physical activity could essentially translate into better quality of life and increased time spent in good health. We expect that this benefit would translate into lower overall health care costs."

Osteoarthritis is "a major cause of disability, and its prevalence is on the rise due to the aging population and the obesity epidemic. Inactivity is also a major problem in the United States. This is a significant economic burden as well because of the disability and the many health issues associated with inactivity as well as lost productivity and diminished quality of life," noted Dr. Sun, a medical resident and research trainee at Northwestern Feinberg School of Medicine, Chicago.

Doug Brunk/IMNG Medical Media

The study involved analysis of data from the National Institutes of Health–funded Osteoarthritis Initiative (OAI) to gather information on the physical activity levels of more than 4,700 adults, most of whom were aged older than 65 years and more than 40% of whom had a body mass index over 30 kg/m², with or at risk for knee osteoarthritis.

The researchers set out to determine whether meeting the 2008 physical activity guidelines from the Department of Health and Human Services would translate into better overall quality of life and whether interventions to improve physical activity level correlate to better quality-adjusted life years (QALYs).The HHS guidelines recommend 150 minutes of moderate to vigorous activity per week performed in sessions lasting at least 10 minutes each. "An example of moderate activity would be walking briskly as if you were late to an appointment," Dr. Sun said.

The researchers used accelerometers to measure the physical activity level in 1,794 OAI study participants over the course of 1 week and placed them into one of three groups: 235 who met the HHS exercise guidelines of 150 minutes of moderate to vigorous activity, 763 who were "insufficiently active" (engaging in some but fewer than 150 minutes of moderate to vigorous exercise per week), and 796 who were inactive (engaging in no moderate to vigorous exercise per week). Health-related utility scores used to calculate QALYs were measured at the beginning of the study and 2 years later.

Overall, QALYs were significantly better with increasing level of physical activity, Dr. Sun reported. "This was a graded relationship, meaning that [people] in the middle group who had some [level of exercise] but not enough to meet guidelines had significantly better overall quality of life compared with the inactive group," she said. Specifically, after adjustment for socioeconomic and health factors over the 2-year period, people who met the HHS exercise guidelines had QALYs that were 0.11 higher compared with those who were inactive. At the same time, those in the insufficiently active group had QALYs that were 0.058 higher compared with those who were inactive.

"The most active group experienced the most benefit," Dr. Sun said. "The improvement was meaningful and translated into roughly an additional 10-20 days of perfect health in a year. We estimate that if an intervention could move someone out of the inactive group and cost less than $1,450 per person per year, that intervention would be considered cost-effective."

The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Osteoarthritis patients who meet federal guidelines for exercise have more days of perfect health per year than do their sedentary counterparts, results from a novel study suggest.

"Our findings support interventions that help older adults to increase their physical activity level, even if guidelines are not fully met," Dr. Kai Sun said during a press briefing at the annual meeting of the American College of Rheumatology. "Increased physical activity could essentially translate into better quality of life and increased time spent in good health. We expect that this benefit would translate into lower overall health care costs."

Osteoarthritis is "a major cause of disability, and its prevalence is on the rise due to the aging population and the obesity epidemic. Inactivity is also a major problem in the United States. This is a significant economic burden as well because of the disability and the many health issues associated with inactivity as well as lost productivity and diminished quality of life," noted Dr. Sun, a medical resident and research trainee at Northwestern Feinberg School of Medicine, Chicago.

Doug Brunk/IMNG Medical Media

The study involved analysis of data from the National Institutes of Health–funded Osteoarthritis Initiative (OAI) to gather information on the physical activity levels of more than 4,700 adults, most of whom were aged older than 65 years and more than 40% of whom had a body mass index over 30 kg/m², with or at risk for knee osteoarthritis.

The researchers set out to determine whether meeting the 2008 physical activity guidelines from the Department of Health and Human Services would translate into better overall quality of life and whether interventions to improve physical activity level correlate to better quality-adjusted life years (QALYs).The HHS guidelines recommend 150 minutes of moderate to vigorous activity per week performed in sessions lasting at least 10 minutes each. "An example of moderate activity would be walking briskly as if you were late to an appointment," Dr. Sun said.

The researchers used accelerometers to measure the physical activity level in 1,794 OAI study participants over the course of 1 week and placed them into one of three groups: 235 who met the HHS exercise guidelines of 150 minutes of moderate to vigorous activity, 763 who were "insufficiently active" (engaging in some but fewer than 150 minutes of moderate to vigorous exercise per week), and 796 who were inactive (engaging in no moderate to vigorous exercise per week). Health-related utility scores used to calculate QALYs were measured at the beginning of the study and 2 years later.

Overall, QALYs were significantly better with increasing level of physical activity, Dr. Sun reported. "This was a graded relationship, meaning that [people] in the middle group who had some [level of exercise] but not enough to meet guidelines had significantly better overall quality of life compared with the inactive group," she said. Specifically, after adjustment for socioeconomic and health factors over the 2-year period, people who met the HHS exercise guidelines had QALYs that were 0.11 higher compared with those who were inactive. At the same time, those in the insufficiently active group had QALYs that were 0.058 higher compared with those who were inactive.

"The most active group experienced the most benefit," Dr. Sun said. "The improvement was meaningful and translated into roughly an additional 10-20 days of perfect health in a year. We estimate that if an intervention could move someone out of the inactive group and cost less than $1,450 per person per year, that intervention would be considered cost-effective."

The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Osteoarthritis patients who meet federal guidelines for exercise have more days of perfect health per year than do their sedentary counterparts, results from a novel study suggest.

"Our findings support interventions that help older adults to increase their physical activity level, even if guidelines are not fully met," Dr. Kai Sun said during a press briefing at the annual meeting of the American College of Rheumatology. "Increased physical activity could essentially translate into better quality of life and increased time spent in good health. We expect that this benefit would translate into lower overall health care costs."

Osteoarthritis is "a major cause of disability, and its prevalence is on the rise due to the aging population and the obesity epidemic. Inactivity is also a major problem in the United States. This is a significant economic burden as well because of the disability and the many health issues associated with inactivity as well as lost productivity and diminished quality of life," noted Dr. Sun, a medical resident and research trainee at Northwestern Feinberg School of Medicine, Chicago.

Doug Brunk/IMNG Medical Media

The study involved analysis of data from the National Institutes of Health–funded Osteoarthritis Initiative (OAI) to gather information on the physical activity levels of more than 4,700 adults, most of whom were aged older than 65 years and more than 40% of whom had a body mass index over 30 kg/m², with or at risk for knee osteoarthritis.

The researchers set out to determine whether meeting the 2008 physical activity guidelines from the Department of Health and Human Services would translate into better overall quality of life and whether interventions to improve physical activity level correlate to better quality-adjusted life years (QALYs).The HHS guidelines recommend 150 minutes of moderate to vigorous activity per week performed in sessions lasting at least 10 minutes each. "An example of moderate activity would be walking briskly as if you were late to an appointment," Dr. Sun said.

The researchers used accelerometers to measure the physical activity level in 1,794 OAI study participants over the course of 1 week and placed them into one of three groups: 235 who met the HHS exercise guidelines of 150 minutes of moderate to vigorous activity, 763 who were "insufficiently active" (engaging in some but fewer than 150 minutes of moderate to vigorous exercise per week), and 796 who were inactive (engaging in no moderate to vigorous exercise per week). Health-related utility scores used to calculate QALYs were measured at the beginning of the study and 2 years later.

Overall, QALYs were significantly better with increasing level of physical activity, Dr. Sun reported. "This was a graded relationship, meaning that [people] in the middle group who had some [level of exercise] but not enough to meet guidelines had significantly better overall quality of life compared with the inactive group," she said. Specifically, after adjustment for socioeconomic and health factors over the 2-year period, people who met the HHS exercise guidelines had QALYs that were 0.11 higher compared with those who were inactive. At the same time, those in the insufficiently active group had QALYs that were 0.058 higher compared with those who were inactive.

"The most active group experienced the most benefit," Dr. Sun said. "The improvement was meaningful and translated into roughly an additional 10-20 days of perfect health in a year. We estimate that if an intervention could move someone out of the inactive group and cost less than $1,450 per person per year, that intervention would be considered cost-effective."

The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com