Abstract

OA is the most common form of arthritis. It results from the degradation of the joint through overuse or injury. It is estimated that 30.8 million adults in the United States suffer from OA. Treatment options of OA come in both non-pharmacologic and pharmacologic forms, with varying levels of efficacy for each option depending on the joint it is intended to be used for. In 2019, the American College of Rheumatology (ACR) updated the guidelines for the management of osteoarthritis of the knee, hip, and hand. The guidelines have been updated to state that acetaminophen is no longer the first line option for OA. In addition supplements like glucosamine and chondroitin are also no longer favored for use in the management of OA. This clinical capsule aims to describe the guidelines for OA as outlined by the ACR so that pharmacists in any type of setting, but especially in the community, can recommend appropriate therapy and counsel patients accordingly.

Introduction

Osteoarthritis (OA) is the most common cause of disability in adults, with an estimated prevalence of 30.8 million adults in the United States.(1,2) OA results from the degradation of the joint through overuse or injury, and it is also the most common form of arthritis.(3) The first signs and symptoms of OA are pain, inflammation, and loss of function in the joints, particularly in the knees, hands, and hips. OA is usually differentiated into two categories: primary osteoarthritis and secondary osteoarthritis. Primary osteoarthritis is the result of natural degradation of cartilage within the joint from friction over time; this type is prevalent among older adults. Secondary osteoarthritis is cartilage breakdown that is the result of injury or another disease. Although the two conditions are similar in presentation of symptoms, OA is different from rheumatoid arthritis (RA) because it is not an autoimmune disease, in which a patient’s immune system attacks their own cells, but instead is the result of mechanical breakdown of the joint. Treatment options for OA consist of both non-pharmacologic and pharmacologic therapies, with varying levels of efficacy for each option, depending on the joint it is intended treat. In 2019, the American College of Rheumatology (ACR) released an update for management of OA of the hand, hip, and knee. This was the first update for this guideline since 2012. Among other changes, the guideline now strongly recommends oral nonsteroidal anti-inflammatory drugs (NSAIDs), and it only conditionally recommends acetaminophen for management of hand, knee, and hip OA.(4) This clinical capsule aims to summarize the revised ACR guideline for OA and provide an overview of medications used to manage this chronic condition.

Diagnosis Classification

The ACR guideline differentiates between the different types of OA by anatomic location, such as hand, hip, and knee.(4) Refer to Table 1 for the summary of pharmacologic and nonpharmacologic recommendations for management of OA.

Table 1

Pharmacologic and Non-Pharmacologic Approaches for Hand, Knee, and Hip Osteoarthritis

Pharmacologic and Non-Pharmacologic Approaches for Hand, Knee, and Hip Osteoarthritis
Pharmacologic and Non-Pharmacologic Approaches for Hand, Knee, and Hip Osteoarthritis

Non-Pharmacologic Treatment Options

Non-pharmacologic options strongly recommended by the ACR for treatment of hand, knee, and hip OA include self-efficacy and self-management programs and exercise.(4) Walking, strengthening, neuromuscular training, and aquatic exercise are all favored equally by ACR for knee and hip OA.4 Weight loss, Tai Chi, and cane use are strongly recommended for knee and hip OA, while first carpometacarpal orthosis is strongly recommended for hand OA and tibiofemoral knee brace is strongly recommended for knee OA.(4)

Pharmacologic Treatment Options

NSAIDs

Regardless of the anatomic location, NSAIDs are the mainstay of pharmacologic treatment options for patients with OA. Oral NSAIDs are recommended over other oral medication therapy options.(4) Studies have established the short-term efficacy of oral NSAIDs for osteoarthritis use, but long-term efficacy has not yet been determined.(4)

NSAIDs act as analgesics and anti-inflammatory medications via inhibition of cyclooxygenase (COX) enzymes, COX-1 and COX-2. Ranging from non-selective to selective, NSAID selectivity is based on the NSAID’s relative partialness for the COX-2 enzyme inhibition. For example, celecoxib is a COX-2 selective NSAID, while naproxen is a non-selective NSAID. The selectivity of NSAIDs may influence the risk of gastrointestinal (GI) and cardiovascular events. However, within an NSAID group with similar selectivity, there are still differences to consider, including clinical efficacy and patient tolerability.(5) For instance, although meloxicam and diclofenac are both partially selective NSAIDs with similar efficacy, meloxicam was found to have better GI tolerability than oral diclofenac.(6)

With the wide variety of NSAIDs available, it is important to note that certain NSAIDs may have more favorable side effect profiles than others. Non-selective NSAIDs, such as naproxen and ibuprofen, generally have a higher risk of GI bleeding compared to selective NSAIDs, such as celecoxib. However, celecoxib is associated with an increased risk of cardiovascular events, including myocardial infarction and stroke, compared to non-selective NSAIDs.(7) Given the side effects and risks associated with chronic NSAID use, NSAID doses should be as low as possible and given for the shortest duration necessary, while maintaining adequate analgesic and anti-inflammatory activity. NSAID selection should account for the patient’s past medical history to avoid worsening of cardiovascular or GI conditions.

Topical NSAIDs are strongly recommended for patients with knee OA and conditionally recommended for patients with hand OA due to lack of evidence and practical reasons.(4) It may be difficult to achieve therapeutic benefit with topical NSAIDs for hand OA depending on the frequency of hand washing.(4) Refer to Tables 2 and 3 for oral and topical NSAID treatment options.

Table 2

Selected Oral NSAIDs for Osteoarthritis

Selected Oral NSAIDs for Osteoarthritis
Selected Oral NSAIDs for Osteoarthritis
Table 3

Topical NSAIDs for Osteoarthritis

Topical NSAIDs for Osteoarthritis
Topical NSAIDs for Osteoarthritis

Intra-articular injections

Intra-articular glucocorticoid injections are strongly recommended for patients with knee or hip OA.(4) Studies have demonstrated short-term efficacy in knee OA.(8,9) However, there is a lack of evidence for the use of intra-articular glucocorticoid injections in patients with hand OA. There is insufficient evidence to determine whether short-acting or long-acting options are superior when it comes to duration of action.(4) Compared to other injection options, intra-articular glucocorticoid injections are conditionally recommended for patients with knee, hip, or hand OA over other injections, such as hyaluronic acid.(4) This conditional recommendation is due to the higher quality of evidence for efficacy of glucocorticoid injections than other agents and few direct comparisons performed.(4)

Intra-articular hyaluronic acid injections are conditionally recommended against usage in patients with knee and hand OA, and strongly recommended against usage in patients with hip OA.(4,10) In cases in which glucocorticoid injections or other interventions fail or patients have an inadequate response to non-pharmacologic interventions or topical or oral NSAIDs, intra-articular hyaluronic acid injections can be considered.(4) Due to the limited trials and lack of efficacy, intra-articular botulinum toxin injections are conditionally recommended against use in patients with knee or hip OA.(4)

Acetaminophen

Acetaminophen, although a commonly used medication, is only conditionally recommended for knee, hip, and hand OA.(4) It is preferred to use acetaminophen in patients who have intolerance for or contraindications to NSAIDs. However, other pharmacologic options may be preferred since studies indicate that acetaminophen does not provide clinically significant pain relief for its users.(4) With the risk of hepatotoxicity from acetaminophen, it is advised to monitor the patient for signs and symptoms of liver dysfunction, especially with chronic use at the maximal recommended daily dose.(11,12) The minimal benefit compounded with the risk of hepatotoxicity for patients with OA makes acetaminophen a conditionally recommended treatment option.(4) Refer to Table 4 for the non-NSAID OA treatment options.(4)

Table 4

Non-NSAID Options for Osteoarthritis

Non-NSAID Options for Osteoarthritis
Non-NSAID Options for Osteoarthritis

Duloxetine

Duloxetine is another conditionally recommended treatment option for OA, primarily in the knee. Although few studies have been conducted regarding duloxetine’s benefit for hand and/or hip OA, it is nonetheless conditionally recommended for these conditions as well.(4) Studies indicate that duloxetine has clinically significant benefits of lowering pain in knee OA patients.(13) Duloxetine has also demonstrated an improvement in quality of life in patients with knee OA.(13) Ongoing studies have not been conducted for a sufficient duration to determine whether duloxetine is superior to NSAIDs.(13) It is, however, associated with minor GI side effects, such as nausea, constipation, and decreased appetite.(13) As a result, the benefits of duloxetine make it a possible treatment option for knee OA when other pharmacologic treatment options cannot be used.(4,13,14)

Tramadol

Tramadol is a conditionally recommended option for knee, hip, or hand OA.(4) It is the only opioid that is recommended for OA, possibly due to having a lower risk of addiction and respiratory depression when compared to other opioids.(4,15) Although tramadol has demonstrated moderate benefit in managing OA pain, one study found that mortality rates were significantly higher among patients prescribed tramadol when compared to those prescribed NSAIDs.(15) The patients receiving tramadol, however, had more severe comorbid conditions compared to those receiving NSAIDs.(15) As there is a concern for GI bleeding, cardiovascular events, and nephrotoxicity with NSAID use, tramadol may be a potential alternative option for patients at higher risk for these adverse events.(15,16) It is important to note that high-quality evidence is not available regarding tramadol use for over 1 year.(4)

Topical capsaicin

Topical capsaicin is conditionally recommended for knee OA, but conditionally recommended against use in hand OA.(4) No recommendation was made for hip OA due to a lack of quality evidence and a belief that the joint is simply too deep under the skin for topical capsaicin to provide significant benefit.(4) While studies have shown that topical capsaicin has comparable benefits in OA when compared to topical NSAIDs, its use should remain limited to knee OA.(4)

Chondroitin sulfate

Although chondroitin sulfate is strongly recommended against use for both knee and hip OA, it is conditionally recommended to treat hand OA.(4) Chondroitin sulfate use in OA does not result in adverse events in patients, but it also does not show significant benefit in hip or knee OA patients.(17) The use of chondroitin sulfate was found to be safe in treating hand OA and resulted in benefit for the patients in both function and pain management.(18) Many formulations of chondroitin also contain glucosamine. It is important to note that ACR strongly recommends against use of glucosamine in patients with OA of the knee, hip, or hand.(4) Although some patients may perceive benefit from glucosamine, studies point to a lack of efficacy and more to a placebo effect when it comes to glucosamine use for management of OA.(4)

Conclusion

Osteoarthritis is caused by degradation of the joint through overuse or injury, and it is the most prevalent type of arthritis. Based on the updated 2019 ACR guideline for osteoarthritis management, NSAIDs have replaced acetaminophen as the first-line option for OA. The strength of recommendation for the pharmacologic and non-pharmacologic options varies based on the anatomic location of OA. Strong recommendations are made for exercise and weight loss in patients with knee or hip OA.(4) Self-efficacy and self-management programs, as well as oral NSAIDs, are strongly recommended for hand, knee, and hip OA.(4) As some of the most accessible health care providers, pharmacists are ideally positioned to educate patients about the non-pharmacologic and pharmacologic therapies used in the management of patients with OA.

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About the Authors

Caroline Sun, PharmD, is a recent graduate of Chapman University School of Pharmacy, Class of 2021. She is a current PGY-1 resident at VA Northern California Health Care System and is active in CSHP and ASHP. Dr. Sun has no conflicts of interest to report.

Dennis Dang, PharmD, is a recent graduate of Chapman University School of Pharmacy, Class of 2021. He is a pharmacist graduate intern at Rite Aid. Dr. Dang has no conflicts of interest to report.

Jelena Lewis, PharmD, APh, BCACP, is an Assistant Professor of Pharmacy Practice at Chapman University School of Pharmacy and a faculty in residence at Providence Medical Foundation. She is active in APhA and currently serves as the APhA-APPM SIG Coordinator for the Medical Home/ACO SIG. Dr. Lewis has no conflicts of interest to report.