Optimizing Individualized Management of OSTEOARTHRITIS

FACULTY:

Leonard M. Fromer, MD, FAAFP – Program Chair
Associate Clinical Professor;
University of California, Los Angeles;
Los Angeles, California

Steven B. Abramson, MD
Professor of Medicine and Pathology;
Vice Dean for Education, Faculty and Academic Affairs;
Director, Division of Rheumatology;
New York University School of Medicine and The NYU-Hospital for Joint Diseases;
New York, New York

Kenneth C. Jackson, II, PharmD
Assistant Dean for Program Development;
Associate Professor;
Pacific University School of Pharmacy;
Hillsboro, Oregon

Laurajo Ryan, PharmD, MSc, BCPS, CDE
Clinical Assistant Professor;
University of Texas at Austin College of Pharmacy;
University of Texas Health Science Center;
San Antonio, Texas

FINANCIAL DISCLOSURE STATEMENTS:

Leonard M. Fromer, MD, FAAFP, has disclosed no relevant financial relationships.
Steven B. Abramson, MD, has disclosed no relevant financial relationships.
Kenneth C. Jackson, II, PharmD, has disclosed no relevant financial relationships.
Laurajo Ryan, PharmD, MSc, BCPS, CDE, has disclosed no relevant financial relationships.

Curatio CME Institute

Barbara Bekiesz, Editor, has disclosed no relevant financial relationships.
Matthew D. Horn, MD, Medical Director, has disclosed no relevant financial relationships.
Robert W. Rhoades, Medical Writer, has disclosed no relevant financial relationships.
Derek Warnick, CME Director, has disclosed no relevant financial relationships.

U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacists

Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 430-000-09-012-H01-P; 430-000-09-012-H01-T
Credits: 2.0 hours (0.20 ceu)

Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists and pharmacy technicians. Estimated time to complete this activity is 120 minutes.

Exam processing and other inquiries and booklet orders to:
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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

GOAL:

To provide direction to pharmacists and pharmacy technicians regarding optimizing individual management of osteoarthritis (OA).

OBJECTIVES: 

After completing this activity, the participant should be able to:

1. Assess the impact of OA*
2. Discuss the clinical aspects of OA*
3. Describe pharmacologic management of OA*
4. Discuss opportunities and perspectives of OA management.

*Also applies to pharmacy technicians.

Diagnosis and Management of Osteoarthritis

Osteoarthritis (OA) is a leading cause of disability in North America. Many persons with OA are not diagnosed, however, and therefore are not effectively treated. In fact, many patients do not even seek out a formal diagnosis for their OA symptoms. Instead, they simply make a presumptive self-diagnosis and self-treat. In one study, 25% of patients over 55 years of age reported knee pain of at least 4 weeks’ duration in the previous year, yet only 15% of them had consulted their family physician for this symptom.¹ There is obviously room for substantial improvement in the identification and treatment of individuals with OA.

Pharmacists have the potential to play an important role in improving care for these patients.² Pharmacists are more influential in identifying and managing OA patients than generally recognized. Individuals in the community have easy and direct access to pharmacists and often consult with them on the use of over-the-counter (OTC) analgesics.² Such consultation is likely responsible for a large portion of the use of OTC analgesics among people with OA who have never received a formal diagnosis. Similarly, pharmacists are likely to refer individuals to their physicians when OTC analgesics are ineffectual. Pharmacists are thus ideally positioned to identify patients with OA and to provide advice about therapy. A recent study demonstrated that pharmacists are capable of identifying more than 80% of patients with OA.² In their nondispensing (ie, advisory) role, pharmacists have the potential to improve patient outcomes related to medication use.^3,4 Clinical pharmacists have also long been involved in interdisciplinary care teams, whereby they play a significant role in therapy selection. It is only more recently that these contributions from pharmacists have gained wider recognition from the rest of the medical community and the population in general. As pharmacists increase their knowledge of the issues in OA management, their involvement in interdisciplinary care models holds the potential to greatly improve the care of patients with OA.

This article presents information on OA relevant to the expanded role of pharmacists in OA management. It focuses on the epidemiology and pathophysiology of OA, the presentation of patients with this disease, and treatment alternatives for the management of OA-related pain.

Assessing the Impact of OA

The prevalence of OA in the United States is very high, and it can be expected to increase as the population ages. The estimated lifetime risk for symptomatic OA of the knee is 44.7%, and this risk increases to 56.8% in individuals who have a history of knee injury.⁵ The Centers for Disease Control and Prevention estimate that OA affects 13.9% of the US population [.greaterequal]25 years of age and 33.6% of individuals [.greaterequal]65 years of age.⁶ The most common site of OA is the knee; knee OA affects 16% of the population [.greaterequal]45 years of age.⁶ However, OA also occurs frequently at other sites, including the hand (8% of individuals [.greaterequal]60 years of age) and hip (4.4% of people [.greaterequal]55 years of age).⁶

It is important to recognize the link between OA and age because clinicians will encounter a growing number of people with OA as the population ages. Age and other risk factors for OA are summarized in FIGURE 1.⁷ Obesity is a significant risk factor for the development of symptomatic OA of the knee. The lifetime risk for OA of the knee is 30.2% in individuals who have normal body weight or are underweight (body mass index [BMI] <25 kg/m²), but it is 46.9% in those who are over-weight (BMI 25 to <30 kg/m²).⁵ This risk increases to 60.5% in obese individuals (BMI [.greaterequal]30 kg/m²). Presence of metabolic syndrome (a combination of abdominal obesity, elevated triglycerides, low levels of high-density lipoprotein cholesterol, high blood pressure, and hyperglycemia) is also associated with high risk for OA. An estimated 62.6% of individuals with OA have metabolic syndrome.⁸

A long-term history of exercise may increase the risk for OA, but the exact nature of the association is controversial. Contrary to the common misconception that exercise may damage joints, available evidence suggests that, in the absence of injury, exercise may decrease the risk for OA.⁹ In the elderly, changes in the mechanical loading of the knee that result from alterations in gait may contribute to the increased prevalence of OA of the knee in this population.¹⁰ A significantly increased risk for the development of OA of the hip has been attributed to an occupational history of heavy physical stress and to a history of major musculoskeletal injuries.¹¹

Osteoarthritis results in a high disability burden for patients. Osteoarthritis is among the top five causes of disability: 80% of patients with OA have some degree of movement limitation, 11% require help with personal care, and 25% are unable to perform major activities of daily living.⁶ Patients with OA have reduced quality of life relative to the general population, as about 40% rate their health as fair or poor.¹²

Patients with OA are at increased risk for significant psychiatric comorbidities, which may contribute to their impaired quality of life. Affective disorders (eg, depression and anxiety) are common in patients with OA, and the risk increases with the severity of the OA symptoms.¹³ Sleep disorders are also common in OA. In addition, opioid analgesics, commonly used for relief of pain in OA, carry at least some degree of risk for diversion and abuse.¹⁴ Fear of these risks is frequently cited as a reason for undertreatment with these agents.¹⁵ The under-treatment of pain leads to an increased risk of psychiatric comorbidities, increased suffering from the pain of the disease, and a continued decrease in quality of life.

The high prevalence of OA and the substantial disability associated with this disease result in very high direct and indirect costs for this condition. The Arthritis Foundation has estimated that the annual direct and indirect costs of OA in the United States total $128 billion each year.¹⁶ Results from a cohort study of 1258 patients with disabling OA of the hip or knee indicated that the mean annual per-patient direct costs were $2,300, and the indirect costs (mainly from loss of wages) were $12,990. The costs for OA increased with patient age and OA severity, as measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC).¹⁷

The overall cost of treating OA increases with rising comorbidity. Results from one survey among 140 patients with OA indicated that annual treatment costs increased from $2,038 for patients with no comorbidities (36.4% of the cohort) to $4,455 for patients with [.greaterequal]3 comorbidities (20.7% of the cohort).¹⁸

Important Pathophysiologic and Clinical Aspects of OA

Osteoarthritis is not a diagnosis of exclusion. It can be readily diagnosed on the basis of physical examination, patient history, and radiologic evaluation.¹⁹

The most common presenting symptom in patients with OA is pain, occurring in one or more joints, with joint involvement usually being symmetrical. Patients often complain of morning stiffness that resolves with activity. As the disease progresses, joint stiffness may become more prolonged and joint enlargement is also likely to be present. Crepitus (a grating sensation in the joint) and limitations in movement may occur in later-stage disease.¹⁹

The medical history for a patient with suspected OA should include questions about pain, arthralgia, morning stiffness, joint swelling, and weakness. It is also useful to gain information about potential secondary causes of arthritis, which may include obesity, repetitive use, previous trauma, crystal deposition (eg, gout), infection, acromegaly, and rheumatoid arthritis.¹⁹ Inheritable metabolic diseases (eg, alkaptonuria, hemochromatosis, Wilson disease), hemoglobinopathies (eg, sickle cell disease), and neuropathic pain disorders may also lead to joint damage or dysfunction, underlying orthopedic disorders, and bone disease.¹⁹

A thorough medication history is another important line of questioning. Patients with OA often have a long history of using various prescription and OTC products, as well as complementary and alternative therapies. The pharmacist can offer a valuable service to patients by advising them on which therapies have proven efficacy. The pharmacist can also warn patients of the various adverse effects and drug interactions possible with these agents. In their discussions with patients, pharmacists can emphasize the importance of letting the rest of the care team know about concomitant therapies they may be taking, and the pharmacist can even ensure that the other care team members are aware of this history. Additional assessments focusing on the patient’s global functioning, mood, quality of sleep, and other quality-of-life factors should also be obtained to plan for comprehensive care (FIGURE 2).²⁰

Physical examination may reveal apparently normal joints in early-stage disease, but gait may be abnormal if weight-bearing joints are involved. Signs and symptoms that may be present upon physical examination in later-stage OA may include visible and/or palpable osteophytes, joints that are warm to palpation, effusion in superficial joints, range-of-motion limitations secondary to bony restrictions and/or soft tissue contractures, and crepitus.²¹

Radiography is not mandatory for a diagnosis of OA, although it should be used to evaluate involved joints in children, in patients with histories that suggest specific etiologies (eg, trauma), and in individuals who have progressive joint pain, pain at night, or a family history of inflammatory arthritis.¹⁹ Plain film radiographs are useful in differential diagnosis and for monitoring the progression of the disease.²² However, plain radiographs may not reveal significant abnormalities in patients with early-stage disease.²¹ Magnetic resonance imaging is capable of detecting early changes in the joints of patients with OA, but it is seldom used for diagnosis of this disease.²²

There are no definitive clinical laboratory tests for the identification of patients with OA.²¹ Erythrocyte sedimentation rates and levels of C-reactive protein are generally normal in patients with OA, and the synovial fluid does not contain elevated numbers of leukocytes (>2,000/mm³).²³ Synovial fluid evaluation is not generally necessary, but it may be useful for determination of leukocyte counts and crystal detection in the differential diagnosis of OA versus infection and gout. Investigation of various biomarkers has provided some insight into possible mechanisms of bone turnover in OA (eg, cartilage oligomeric matrix protein, antigenic keratan sulphate, hyaluronan, human cartilage glycoprotein-39, type III collagen Npropeptide, and urinary glucosyl-galactosyl pyridinoline), but, as yet, none of these is clinically useful.²³

As mentioned, pain is one of the cardinal symptoms of OA. Assessment of patients’ pain severity is thus an important part of the initial evaluation. The measurement of pain involves many facets, including intensity, location, duration, quality, and aggravating or alleviating factors. The chronic pain associated with OA can be assessed with any of a large number of scales, including the WOMAC, the Brief Pain Inventory (BPI), and the McGill Pain Questionnaire.²⁴ The WOMAC also measures functionality, which is not directly a pain assessment. In essence, the WOMAC uses a pain scale to answer questions related to pain and function.

Pathophysiology of OA

Osteoarthritis involves three tissues— bone, articular cartilage, and the synovium—all of which undergo alterations in response to mechanical stress. Mechanical stress, in addition to trauma, joint mis-alignment, surgery, and even genetic predisposition, are all believed to contribute to the development of OA. Much research effort has been devoted to attempts to link these factors to the changes in joint tissues characteristic of OA. It is now known that both osteocytes and chrondrocytes respond to mechanical pressure. Under normal circumstances, this results in increased collagen synthesis and formation of extracellular matrix. However, abnormal mechanical stress can result in the production of substances that can degrade cartilage, such as inflammatory cytokines, including tumor necrosis factor–[.alpha] (TNF-[.alpha]), interleukins (interleukins 1[.beta], 6, and 8), and proteases (eg, matrix metalloproteinase).²⁵

Inflammatory events also contribute to the pain characteristic of OA. Inflammatory molecules, including prostaglandin E1 and leukotriene B4, can sensitize nerve fibers in joints, increasing the response to both painful and nonpainful stimuli. Other inflammatory molecules (eg, bradykinin, histamine, serotonin, prostacyclin) released in joints can cause fibers to signal pain even when the joint is still.²⁶

It has also been suggested that angiogenesis (formation of new blood vessels) may contribute to the progressive joint damage and pain in OA. Inflammatory cells, such as macrophages, can stimulate angio-genesis by releasing vascular endothelial growth factor (VEGF); TNF-[.alpha] also stimulates release of this growth factor from chrondrocytes. Stimulation of new blood vessel formation by VEGF can lead to ossification and the formation of osteophytes. The presence of new blood vessels can lead to pain as a result of structural reorganization of the joint.²⁶

Increased understanding of molecular events involved in the pathobiology of OA has prompted the development of disease-modifying OA drugs. Many of these agents (eg, matrix metalloproteinase inhibitors, TNF-[.alpha] inhibitors, interleukin-1 inhibitors) are aimed at blocking the actions of the inflammatory cytokines and degradative enzymes involved.^25,27 These drugs may also decrease the pain experienced by OA patients.

Pharmacotherapy for Pain Management in the Patient With OA

Pain control should be a primary focus in the overall management of patients with OA because it has been repeatedly shown that the achievement of significant pain relief is associated with significant improvements in quality of life for this population.^28,29 A very wide range of analgesic agents has been employed for pain management in patients with OA. The most commonly used oral medications are acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase 2-selective agents (COX-2 inhibitors), and opioids. Each class of agents is associated with risks for specific adverse events. An important point to remember is that drug interactions are common with all of these agents, and particularly in the older patient population, in whom polypharmacy is common. Recommendations from the American College of Rheumatology (ACR) for the management of pain in patients with OA are summarized in TABLE 1.³⁰

Oral Agents

Acetaminophen Acetaminophen is recommended as first-line treatment for OA by the ACR.³⁰ It is modestly effective for relieving pain and decreasing stiffness, but it often fails to control severe pain.^21,31 Meta-analysis of results from randomized clinical trials has shown that acetaminophen is less effective overall than NSAIDs in terms of pain reduction, improvement in global assessment, and improvement in functional status.³² Hepatotoxicity is the most important adverse effect of acetaminophen. The drug should be used with caution in patients who have liver disease and in those who chronically abuse alcohol, regardless of whether or not they have hepatic dysfunction.²¹

NSAIDs and Selective COX-2 Inhibitors Both NSAIDs and selective COX-2 inhibitors provide significant pain relief in patients with OA. However, nonselective NSAIDs are associated with an increased risk for gastrointestinal bleeding (1% to 3% of patients).²¹ Selective COX-2 inhibitors were developed to selectively inhibit COX-2 and preserve the activity of COX-1, which catalyzes the synthesis of prostaglandins that protect the gastric mucosa. Selective COX-2 inhibitors are as effective as traditional NSAIDs for the treatment of OA pain.²¹

Both conventional NSAIDs and selective COX-2 inhibitors have become the subject of significant controversy because of evidence linking their use to cardiotoxicity. Therefore, it is recommended that these agents be used for only limited periods of time, particularly in patients with cardiovascular disease.^21,31 A meta-analysis of studies investigating the link between NSAIDs or COX-2 inhibitors and heart failure showed that both classes of agents increase the risk of heart failure similarly.³³

Although the overall risk was considered to be relatively small, the risk increases with pre-existing cardiac disease. The Working Group on Pain Management recommends that NSAIDs and selective COX-2 inhibitors be avoided in patients at risk for cardiac or renal disease.³⁴ Product labeling approved by the Food and Drug Administration, along with several guidelines such as those published by the Osteoarthritis Research Society International (OARSI), do not distinguish between NSAIDs and selective COX-2 inhibitors in terms of cardiac risks.^35,36

Opioids, Including Tramadol

Tramadol and full-agonist opioid analgesics are recommended for the treatment of moderate-to-severe pain related to OA.³⁴

Tramadol is a centrally acting agent that exhibits two distinct mechanisms of action: binding to [.proportional]-opioid receptors and blocking the neuronal uptake of serotonin and norepinephrine.²¹

Meta-analysis of clinical trial results indicates that tramadol or tramadol plus acetaminophen decreases pain intensity, produces symptom relief, and improves function in patients with OA, but these benefits are modest.³⁷ The most common adverse events in patients treated with tramadol include constipation, nausea, dizziness, headache, somnolence, and vomiting.²¹

The essential mechanism of action of full-agonist opioid analgesics, as the nomenclature implies, occurs through binding to opioid receptors. These drugs do not have the analgesic ceilings of the other agents (eg, acetaminophen, NSAIDs/COX-2, tramadol) and are also considered a viable option for the treatment of moderate-to-severe OA pain.³⁴ Opioid analgesics may be considered a component of rational polypharmacy for patients with OA pain that worsens or that cannot be controlled by acetaminophen, NSAIDs, or tramadol, either alone or in combination. Adverse effects of opioids include respiratory depression, sedation, dizziness, and constipation. With the exception of constipation, tolerance to these effects often develops with continued treatment.²¹

Both patients and physicians alike share concerns about diversion and abuse of opioid analgesics.^38,39 Approaches that have been taken to decrease these risks include the development of extended-release formulations and other abuse-resistant formulations.⁴⁰ Extended-release opioid formulations may also increase convenience for patients as well as provide better round-the-clock pain control.⁴¹ Programs that involve agreements with patients regarding the use of opioids and also adherence monitoring have been shown to reduce opioid abuse up to 50%.⁴²

Agents Directed at Neuropathic Pain It is now recognized that OA-related pain may have a neuropathic component (ie, resulting from nervous system reorganization and resultant abnormal pain signaling). Agents that have been used in the treatment of neuropathic pain, although not yet studied extensively in OA, include anticonvulsants, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, N-methyl-D-aspartate antagonists, and ion channel blockers.⁴¹

Intra-articular Agents Intra-articular agents are primarily used to decrease inflammation and improve function in patients with OA, but they have also been shown to relieve pain. Intra-articular injections of corticosteroids are used primarily in patients with OA of the knee. In studies, they have been shown to provide significant pain relief versus placebo. However, this pain relief is short lived, reaching maximal effect at 2 to 3 weeks postinjection.³¹

Viscosupplementation with hyaluronic acid-based products provides pain relief similar to that achieved with NSAIDs and with a longer duration of action than with intra-articular corticosteroids.³¹ Intra-articular injections of opioids and the inter-leukin-1 receptor antagonist anakinra have also been demonstrated to provide pain relief in patients with OA of the knee. The pain relief with anakinra appears to be long lasting (up to 3 months), while that with opioids is short lived (lasting only several days). However, the studies on intra-articular anakinra and opioids involved small numbers of subjects, and, in the case of anakinra, no placebo comparison was made.^21,31 Further studies of these agents are needed.

Topical Agents

Topical agents are effective for the treatment of OA, and they have the added benefit of reducing the risk for interaction with other drugs that the patient may be taking. Elderly individuals, who are most at risk for the development of OA, are also the segment of the OA population most likely to be taking a large number of medications.^43,44 Topical analgesics are thus particularly suited for use in elderly patients because they decrease the risk for systemic adverse effects.⁴⁴ Topical NSAIDs, lidocaine, capsaicin, and salicylate/menthol have all been shown to be effective for the treatment of peripheral pain.⁴⁵ Topical NSAIDs appear to be as effective as oral drugs for relieving OA-associated pain, and they are less likely than oral agents to result in systemic effects, including gastrointestinal, cardiac, and renal events.²¹

Many studies have proven the efficacy of topical NSAIDs in the short term, up to 2 weeks. One study of patients with OA of the knee showed greater efficacy in pain relief with topical diclofenac for up to 12 weeks versus placebo.⁴⁶ Longer-term studies with diclofenac are lacking. Lidocaine 5% patches have also been demonstrated to be safe and effective for the treatment of OA pain; the most common adverse event occurring with these patches is local skin irritation.²¹ Two published studies, each of 2 weeks’ duration, have demonstrated the efficacy of lidocaine patches in reducing the pain of OA.^47,48 A third study showed similar efficacy between lidocaine patches and oral celecoxib for up to 12 weeks.²¹ Capsaicin relieves pain by depleting neurotransmitters in primary sensory fibers and reversibly decreasing their density. Capsaicin has been used effectively in patients with OA. Its most common adverse effects are a burning, tingling sensation and allodynia at the application site.⁴⁴

Adjuvant Therapies

Sleep disturbances and mood disorders are common in patients with OA and should be treated if present.^49,50 Medications suitable for the treatment of sleep disorders in OA patients include nonbenzodiazepine agonists (zolpidem, zopiclone, zapelon) and benzodiazepines (lorazepam, temazepam).⁴⁹ Various classes of agents are suitable for treating depression. These include tri-cyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and others.⁵¹

Emerging Treatments and Concepts for Pain Treatment

New agents for pain management in patients with OA are in development. These include the new abuse-resistant formulations of opioid analgesics mentioned previously.⁴⁰ An antibody directed against nerve growth factor, tanezumab, has been shown to improve WOMAC scores better than placebo in patients with OA. In addition, a bradykinin-B₂ receptor antagonist has been found to be effective for the treatment of OA of the knee following intra-articular injection.²⁷ Novel topical agents in development may be particularly useful in elderly patients when drug-drug interactions related to polypharmacy need to be avoided.

Nonpharmacologic Interventions in OA
Addressing Risk Factors

Age- and genetics-related risk factors for OA cannot be modified, but others, such as obesity, metabolic syndrome, and joint injuries, can be. Weight reduction alone will significantly decrease pain scores and increase ambulation speed in obese patients with OA of the knee.⁵² OA is associated with high loads on joints and misalignment that can result in progressive injury. Use of walking aids, bracing, and taping can decrease pain and improve function in patients with OA.⁵³

Educational and Physical Interventions

Other nonpharmacologic interventions are also recommended for patients with OA (TABLE 2).³⁰ These include self-management and exercise programs (both aerobic and muscle-strengthening), occupational and physical therapy, use of appropriate assistive devices, Tai Chi, acupuncture, diathermy, and balneotherapy.^30,54-56

Nutraceuticals

Nutraceuticals and specific foods have been used extensively to relieve symptoms of OA, but there is generally only modest evidence from controlled clinical trials to support their use. Glucosamine is an essential component of proteoglycans that are a key component of cartilage, and chondroitin is a glycosaminoglycan found in cartilage and connective tissue. A recent review of the literature supports the conclusion that both of these agents provide significant pain relief in patients with OA.⁵⁷ Dimethyl sulfoxide and methylsulfonylmethane have also been employed to treat OA, but available data cannot support a positive recommendation for the use of either agent.⁵⁸ Foods and food-derived compounds that have been studied in the treatment of OA include ginger, avocado, and soybean. In a randomized, controlled trial, ginger was not found to provide a statistically significant difference from placebo in relieving pain. The efficacy of an avocado and soybean compound is, however, supported by results from clinical trials. The combination of avocado and soybean has been shown to provide symptom relief and decrease NSAID use in two well-controlled clinical trials.⁵⁹

Current OA Treatment Guidelines

Major guidelines for the treatment of OA carry similar recommendations for using a combination of nonpharmacologic and pharmacologic strategies. All of the guidelines also recommend a stepped approach to pharmacotherapy for pain management. Acetaminophen is first-line treatment. Nonsteroidal anti-inflammatory drugs, administered at the lowest effective doses, are recommended for patients who do not respond to acetaminophen. Opioids are reserved for patients in whom NSAIDs are contraindicated, ineffective, or poorly tolerated.^30,35,36,60 The pyramid in FIGURE 3 depicts the recommended step-wise approach to OA management.⁶¹

New Opportunities and Perspectives in OA Management

Current approaches to the management of patients with OA emphasize the importance of patient-centered therapy that takes into account patient needs and preferences and allows patients to make informed decisions about their care and participate in the development of a management plan. Care should be holistic and include consideration of the patient’s social situation and support network, as well as comorbidities. Patients should be followed closely by the treatment team.²⁰

As emphasized in all of the guidelines, interventions for OA should be based on severity of disease.⁶¹ Generally, a combination of nonpharmacologic and pharmacologic treatments will be required to achieve optimal outcomes in most patients.³⁵ Combinations of topical and oral pharmacologic agents may be useful for optimizing pain relief in some patients.³⁵

Specific approaches to care include the patient-centered medical home model and the regular, planned-care model. The patient-centered medical home model emphasizes the employment of a treatment team led by the patient’s personal physician to provide patient-centered care. This approach focuses on making care convenient for the patient and ensuring continuity by providing the patient with access to one physician.⁶² The regular planned-care model also uses a team-based approach and emphasizes regularly scheduled OA management that is not limited solely to urgent interventions or the treatment of pain.

Pharmacoeconomic Considerations

The cost-effectiveness of different pharmacologic approaches to the management of OA has been evaluated in a large number of studies. Available evidence suggests that acetaminophen, followed by an OTC NSAID, is the most cost-effective option for achieving pain relief for patients with pain related to OA of the knee.¹³ Unfortunately, there are no published comparisons of the cost-effectiveness of different oral and topical treatments for OA across the entire range of disease and pain severity. Moreover, cost-effectiveness studies comparing pharmacologic and nonpharmacologic treatments for OA are similarly lacking.

Other issues related to cost of care and outcomes for patients with OA include formulary restrictions and substitutions, the impact of benefit design, and the economic impact of adherence to therapy. Results from one retrospective analysis indicated that a three-tiered copayment coverage for anal-gesic agents in which selective COX-2 inhibitors were placed in the highest tier resulted in reduced use of these drugs; this reduced usage extended to patients at high risk for gastrointestinal events.⁶³ Thus, an approach to drug coverage aimed at decreasing cost may have the unintended effect of increasing the risk for adverse events among some patients. Results from another retrospective study revealed an inverse relationship between the number of NSAIDs on formularies and the risk for hospitalizations among patients with OA. This suggests that more restrictive formularies may engender increased health care resource utilization.⁵⁷ In one study, an increase in copayments for OA medications resulted in a significant increase in the number of patients who simply discontinued treatment.⁶⁴ This change in pharmacy benefit was associated with a $971 increase in total treatment costs for patients with OA.

Conclusions

Osteoarthritis is a very common condition in the United States, and it causes significant pain and disability for a very large number of people, particularly the elderly. Optimal management of patients with OA requires integrated therapy involving both pharmacologic and nonpharmacologic interventions. All current treatment guidelines for the management of pain in patients with OA recommend a stepped approach to pharmacotherapy, beginning with acetaminophen as first-line therapy, followed by NSAIDs and opioids, if necessary. Pharmacists are essential members of the diagnostic and treatment team for patients with OA. Pharmacists also provide important support in treatment decision making for patients who may not receive adequate advice from other health care professionals.⁶⁵

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