Osteoarthritis Treatment Options Remain Disappointing

SANTA MONICA, CALIF. – Advances in biomarker research and imaging may eventually make earlier diagnosis of osteoarthritis a reality. Unfortunately, such technologies remain prohibitively expensive for routine use.

And there's another problem: nothing to offer patients by way of an effective early therapy for knee OA.

"Clearly, the benefit of early diagnosis is in the setting of an effective treatment that could prevent progression to more severe changes," Dr. Amanda E. Nelson noted. "So at the present time, when such treatments are not available, the benefit of early diagnosis is really to identify individuals at an early stage when an investigational therapy might be of use, and such individuals can be enrolled in clinical trials.

"In the absence of specific disease-modifying treatments, the extra expense of an MRI for diagnosis is not warranted in daily practice at this time," advised Dr. Nelson of the division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill.

"The ideal therapy for knee OA is to be able to tailor therapy to an individual and their specific set of risk factors," Dr. Nelson said, noting that in such an ideal world, there would not be one OA treatment that was applied to everyone.

What has stymied the development of effective drugs for altering the course of knee OA?

The progress is slow for a few reasons, according to Dr. Nelson. Among them are lack of sensitive, cost-effective early diagnostics to best identify candidates for treatment, medicine's as-yet poor understanding of the causes of progression in OA, and its inability to identify which patients will progress to knee OA. This disease has a very long natural history: An injury in one's 20s may not lead to OA until after age 40 years. These things make trials difficult to conduct and to fund.

So for now, physicians who manage patients with knee OA are left with some poor choices.

Current treatment is directed toward late-stage disease, and by and large these therapies focus on easing pain, not on modifying the course of the disease, Dr. Nelson said at a meeting sponsored by Skin Disease Education Foundation and the University of Louisville.

Corticosteroids have no effect on function, but do relieve pain for 1-3 weeks. Administration of intra-articular hyaluronans eases pain and preserves or improves function for 5-13 weeks, judging from findings of a systematic review (Cochrane Database Syst. Rev. 2006 [doi:10.1002/14651858.CD005328.pub2]).

On the investigational front, at least one phase III trial of the cyclooxygenase/lipoxygenase (COX/LOX) agent licofelone has been completed.

This investigational agent is an anti-inflammatory agent without the adverse effects of COX inhibition. Specifically, licofelone blocks synthesis of leukotriene, which contributes to inflammation and vasoconstriction. Metabolites of leukotriene synthesis cause gastrointestinal damage.

Findings from a trial of 355 patients with knee OA showed that licofelone given in a 200-mg dose twice daily preserved the volume of knee cartilage as well as did naproxen given in a 500-mg dose twice daily, with less GI toxicity. Cartilage volume was assessed using MRI (Ann. Rheum. Dis. 2009;68:938-47).

Another category of symptomatic treatment that has gone through a phase III trial is COX-inhibiting nitric oxide donators (CINODs). These compounds are created by fusing an existing NSAID to nitric oxide. These agents have anti-inflammatory properties similar to those of NSAIDs, but – unlike NSAIDs – CINODS protect the gastric mucosa and acts as both a vasodilator and an inhibitor of platelet aggregation, thereby preventing vascular damage (J. Pharm. Pharm. Sci. 2008;11:81s-110s).

Findings from research using intra-articular injection of the cytokine inhibitor IL-1Ra in humans has been disappointing. The drug did not ease pain at 12 weeks but did provide more short-term pain relief. The role of this agent may prove to be in the prevention of posttraumatic OA if it is given soon enough after injury.

Pain management is one of the major challenges in OA clinical care. "The pain management choices we have are often minimally or not effective and carry with them significant side effects. There are no great answers and a large need for better options," she said.

Some investigators were keeping a close eye on trials of tanezumab, a monoclonal antibody against nerve growth factor that showed early efficacy in OA pain. Although Pfizer Inc. has halted the trials because of increased progression and higher numbers of joint replacement, it is unclear whether that was related to the drug or to increased activity by the study subjects who experienced pain relief.

The SDEF and this news organization are owned by Elsevier. Dr. Nelson reported that her funding sources include a National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases loan repayment grant and an American College of Rheumatology Research and Education Foundation Clinical Investigator Fellowship Award. She reported having no other disclosures to make.

SANTA MONICA, CALIF. – Advances in biomarker research and imaging may eventually make earlier diagnosis of osteoarthritis a reality. Unfortunately, such technologies remain prohibitively expensive for routine use.

And there's another problem: nothing to offer patients by way of an effective early therapy for knee OA.

"Clearly, the benefit of early diagnosis is in the setting of an effective treatment that could prevent progression to more severe changes," Dr. Amanda E. Nelson noted. "So at the present time, when such treatments are not available, the benefit of early diagnosis is really to identify individuals at an early stage when an investigational therapy might be of use, and such individuals can be enrolled in clinical trials.

"In the absence of specific disease-modifying treatments, the extra expense of an MRI for diagnosis is not warranted in daily practice at this time," advised Dr. Nelson of the division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill.

"The ideal therapy for knee OA is to be able to tailor therapy to an individual and their specific set of risk factors," Dr. Nelson said, noting that in such an ideal world, there would not be one OA treatment that was applied to everyone.

What has stymied the development of effective drugs for altering the course of knee OA?

The progress is slow for a few reasons, according to Dr. Nelson. Among them are lack of sensitive, cost-effective early diagnostics to best identify candidates for treatment, medicine's as-yet poor understanding of the causes of progression in OA, and its inability to identify which patients will progress to knee OA. This disease has a very long natural history: An injury in one's 20s may not lead to OA until after age 40 years. These things make trials difficult to conduct and to fund.

So for now, physicians who manage patients with knee OA are left with some poor choices.

Current treatment is directed toward late-stage disease, and by and large these therapies focus on easing pain, not on modifying the course of the disease, Dr. Nelson said at a meeting sponsored by Skin Disease Education Foundation and the University of Louisville.

Corticosteroids have no effect on function, but do relieve pain for 1-3 weeks. Administration of intra-articular hyaluronans eases pain and preserves or improves function for 5-13 weeks, judging from findings of a systematic review (Cochrane Database Syst. Rev. 2006 [doi:10.1002/14651858.CD005328.pub2]).

On the investigational front, at least one phase III trial of the cyclooxygenase/lipoxygenase (COX/LOX) agent licofelone has been completed.

This investigational agent is an anti-inflammatory agent without the adverse effects of COX inhibition. Specifically, licofelone blocks synthesis of leukotriene, which contributes to inflammation and vasoconstriction. Metabolites of leukotriene synthesis cause gastrointestinal damage.

Findings from a trial of 355 patients with knee OA showed that licofelone given in a 200-mg dose twice daily preserved the volume of knee cartilage as well as did naproxen given in a 500-mg dose twice daily, with less GI toxicity. Cartilage volume was assessed using MRI (Ann. Rheum. Dis. 2009;68:938-47).

Another category of symptomatic treatment that has gone through a phase III trial is COX-inhibiting nitric oxide donators (CINODs). These compounds are created by fusing an existing NSAID to nitric oxide. These agents have anti-inflammatory properties similar to those of NSAIDs, but – unlike NSAIDs – CINODS protect the gastric mucosa and acts as both a vasodilator and an inhibitor of platelet aggregation, thereby preventing vascular damage (J. Pharm. Pharm. Sci. 2008;11:81s-110s).

Findings from research using intra-articular injection of the cytokine inhibitor IL-1Ra in humans has been disappointing. The drug did not ease pain at 12 weeks but did provide more short-term pain relief. The role of this agent may prove to be in the prevention of posttraumatic OA if it is given soon enough after injury.

Pain management is one of the major challenges in OA clinical care. "The pain management choices we have are often minimally or not effective and carry with them significant side effects. There are no great answers and a large need for better options," she said.

Some investigators were keeping a close eye on trials of tanezumab, a monoclonal antibody against nerve growth factor that showed early efficacy in OA pain. Although Pfizer Inc. has halted the trials because of increased progression and higher numbers of joint replacement, it is unclear whether that was related to the drug or to increased activity by the study subjects who experienced pain relief.

The SDEF and this news organization are owned by Elsevier. Dr. Nelson reported that her funding sources include a National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases loan repayment grant and an American College of Rheumatology Research and Education Foundation Clinical Investigator Fellowship Award. She reported having no other disclosures to make.

SANTA MONICA, CALIF. – Advances in biomarker research and imaging may eventually make earlier diagnosis of osteoarthritis a reality. Unfortunately, such technologies remain prohibitively expensive for routine use.

And there's another problem: nothing to offer patients by way of an effective early therapy for knee OA.

"Clearly, the benefit of early diagnosis is in the setting of an effective treatment that could prevent progression to more severe changes," Dr. Amanda E. Nelson noted. "So at the present time, when such treatments are not available, the benefit of early diagnosis is really to identify individuals at an early stage when an investigational therapy might be of use, and such individuals can be enrolled in clinical trials.

"In the absence of specific disease-modifying treatments, the extra expense of an MRI for diagnosis is not warranted in daily practice at this time," advised Dr. Nelson of the division of rheumatology, allergy, and immunology at the University of North Carolina at Chapel Hill.

"The ideal therapy for knee OA is to be able to tailor therapy to an individual and their specific set of risk factors," Dr. Nelson said, noting that in such an ideal world, there would not be one OA treatment that was applied to everyone.

What has stymied the development of effective drugs for altering the course of knee OA?

The progress is slow for a few reasons, according to Dr. Nelson. Among them are lack of sensitive, cost-effective early diagnostics to best identify candidates for treatment, medicine's as-yet poor understanding of the causes of progression in OA, and its inability to identify which patients will progress to knee OA. This disease has a very long natural history: An injury in one's 20s may not lead to OA until after age 40 years. These things make trials difficult to conduct and to fund.

So for now, physicians who manage patients with knee OA are left with some poor choices.

Current treatment is directed toward late-stage disease, and by and large these therapies focus on easing pain, not on modifying the course of the disease, Dr. Nelson said at a meeting sponsored by Skin Disease Education Foundation and the University of Louisville.

Corticosteroids have no effect on function, but do relieve pain for 1-3 weeks. Administration of intra-articular hyaluronans eases pain and preserves or improves function for 5-13 weeks, judging from findings of a systematic review (Cochrane Database Syst. Rev. 2006 [doi:10.1002/14651858.CD005328.pub2]).

On the investigational front, at least one phase III trial of the cyclooxygenase/lipoxygenase (COX/LOX) agent licofelone has been completed.

This investigational agent is an anti-inflammatory agent without the adverse effects of COX inhibition. Specifically, licofelone blocks synthesis of leukotriene, which contributes to inflammation and vasoconstriction. Metabolites of leukotriene synthesis cause gastrointestinal damage.

Findings from a trial of 355 patients with knee OA showed that licofelone given in a 200-mg dose twice daily preserved the volume of knee cartilage as well as did naproxen given in a 500-mg dose twice daily, with less GI toxicity. Cartilage volume was assessed using MRI (Ann. Rheum. Dis. 2009;68:938-47).

Another category of symptomatic treatment that has gone through a phase III trial is COX-inhibiting nitric oxide donators (CINODs). These compounds are created by fusing an existing NSAID to nitric oxide. These agents have anti-inflammatory properties similar to those of NSAIDs, but – unlike NSAIDs – CINODS protect the gastric mucosa and acts as both a vasodilator and an inhibitor of platelet aggregation, thereby preventing vascular damage (J. Pharm. Pharm. Sci. 2008;11:81s-110s).

Findings from research using intra-articular injection of the cytokine inhibitor IL-1Ra in humans has been disappointing. The drug did not ease pain at 12 weeks but did provide more short-term pain relief. The role of this agent may prove to be in the prevention of posttraumatic OA if it is given soon enough after injury.

Pain management is one of the major challenges in OA clinical care. "The pain management choices we have are often minimally or not effective and carry with them significant side effects. There are no great answers and a large need for better options," she said.

Some investigators were keeping a close eye on trials of tanezumab, a monoclonal antibody against nerve growth factor that showed early efficacy in OA pain. Although Pfizer Inc. has halted the trials because of increased progression and higher numbers of joint replacement, it is unclear whether that was related to the drug or to increased activity by the study subjects who experienced pain relief.

The SDEF and this news organization are owned by Elsevier. Dr. Nelson reported that her funding sources include a National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases loan repayment grant and an American College of Rheumatology Research and Education Foundation Clinical Investigator Fellowship Award. She reported having no other disclosures to make.