Osteoarthritis affects more than 300 million people worldwide, making it the most common form of arthritis. It is one of the leading causes of disability, specifically among older adults. The most affected joints are those in the hands, knees, and hips, which each requireunique course of treatment.¹ Risk factors for developing osteoarthritis (OA) include age, obesity, sex, occupation, participation in certain sports, history of joint injury or surgery, and genetic predisposition.² Sex, obesity, physical activity, and joint injury history, in addition to vitamin D deficiency, havebeen identified ascharacteristics that may influence the degree of pain OA patients experience.³
Causes of OA include idiopathic or secondary osteoarthritis. In the latter, inflammation, trauma, and metabolic/endocrine disorders commonly contribute to development of osteoarthritic cartilage. Cartilage change occurs due to numerous complex interactions at a molecular level, resulting in joint space narrowing, stiffer and more brittle bones, and synovial thickening. However, pain in OA does not come from cartilage destruction, but rather activation of nearby pain receptors within the joint from bone formation changes. Due to uncertainties behind the mechanism of OA-related pain, developing adequate treatment recommendations for relief is difficult to achieve.³
ACR Guidelines
In 2020, the American College of Rheumatology (ACR) published new guidelines for comprehensive management of hand, hip, and knee osteoarthritis.¹As opposed to its 2012 recommendations,⁴ this update was developed from an internal systematic review of randomized controlled trials (RCTs). Use of an internal review allowed the College’s own literature review team to screen and evaluate evidence, reducing external bias toward conclusions being drawn.
Overall, the updated guideline calls for comprehensive management of OA that considers using educational, behavioral, psychosocial, and physical interventions in addition to pharmacologic therapy. This multimodal approach is designed to address the additional complications that may result from OA such as mood disorders, anxiety, sleep impairment, weight gain, physical impairment, or other comorbidities.²˒⁵ When developing a comprehensive treatment plan for individual patients, clinicians are advised to consider factors such as individual disease status, patient tolerability and preference, presence of other comorbidities, and access to treatment.¹
OA Pharmacologic Management Changes
A key change made upon revision of the guidelines was the strength of recommendations made for pharmacologic management in all types of osteoarthritis. In the 2012 edition, no strong recommendations were made for or against the use of pharmacotherapy agents for hip, hand, or knee osteoarthritis.⁴ Since its 2019 revision, oral NSAIDs, topical NSAIDs, and intraarticular steroids have been changed to strongly recommended as pharmacologic agents for management in at least one type of OA. Although these recommendations were made based on mostly low-to-moderate quality evidence, clear conclusions were still able to be drawn. This review of RCTs was limited to Phase 2 or 3 clinical trials to focus on treatments most likely available to patients.¹ A Voting Panel consisting of interprofessional team members created these recommendations because of overwhelming evidence for efficacy over safety/tolerability concerns found within review of RCTs.
Recommendations that were strongly against certain pharmacologic agents were made based on lack of efficacy in available data, absence of standardization in available preparation, or absence of benefit without harm. Table I summarizes the newly added key recommendations made strongly for or against each type of OA in the 2019 guidelines.
NSAIDs, Acetaminophen, and Duloxetine
The increase in the role of pharmacotherapy in OA management has been most attributable to the conclusive recommendations discussed above. Increased strength of recommendation for oral NSAIDs in all subtypes of OA improves the ability for patients to obtain and adhere to more accessible, and more tolerable, pharmacologic therapy. These recommendations provide clear advice for patients to avoid using supplements such asglucosamine and chondroitin, commonly believed to be effective over-the-counter treatments for OA.
Topical NSAID use is strongly recommended in knee OA, whereasonly conditionally recommended for hand. This is due to limited available evidence showing benefit in hand OA with topical NSAID use, along with practical concerns regarding hand washing and frequent contact interactions.
Review of clinical trials shows limited benefit from acetaminophen use, especially as monotherapy. New recommendations advise patients and providers to avoid using acetaminophen for long-term treatment. In the event of intolerability or contraindications to preferred therapy options, acetaminophen may be an adequate short-term substitute.
Duloxetine use is conditionally recommended for all three types of OA based on evidence of efficacy when used alone and with NSAIDs. However, there are side effect and tolerability concerns.¹
Capsaicin and Supplements
Due to lacking evidence showing efficacy, capsaicin use for hand OA is conditionally recommended against. Risk of eye contamination with topical capsaicin presents practical concerns. However, capsaicin for knee OA is conditionally recommended for, based on small effect sizes showing benefit in the literature available. Colchicine, fish oil, and vitamin D for treatment of OA are conditionally recommended against in all subtypes. These recommendations are based on lacking evidence for efficacy for all three treatments.
Opioids
Opioid use for management of OA pain is mostly recommended against. Tramadol is the preferred opioid for knee and hip OA when other treatment options are not feasible. This recommendation stems from study findings of modest pain relief with tramadol use (3 months to 1 year). Studies evaluating long-term use of opioids, specifically tramadol, are needed. Theseguidelines demonstrate the increased need for pharmacologic management of all three subtypes of disease. In addition to changing pharmacologic recommendations for OA, new approaches to OA treatment may soon reshape future guidelines.¹
Phenotype-Based Treatment
A new approach proposed by the ACR guideline for osteoarthritis management is phenotype-guided therapy. Although research on this approach has made significant strides, its current use has not been applied into expert consensus treatment guidelines.¹˒⁵
Phenotype-guided treatment focuses on tailoring treatment to patients based on categorization into one of three groups: prognostic, mechanistic, and prescriptive phenotypes.⁵ Considering the complex mechanisms behind presentation of osteoarthritis in every patient, utilization of patient-specific treatment plans has grounds for success. This perspective fits into the belief that a comprehensive biopsychosocial model of treatment will yield better patient outcomes.¹ This proposed addition to OA management evaluates patients based on their likelihood of having:
disease progression (prognostic)
benefit from an existing treatment (prescriptive)
need for biologic pathway-specific therapy (mechanistic).⁵
For example, if a provider were to identify a patient with greater sub-chondral bone turnover, this patient would fall into the mechanistic subtype, based on the presence of a patient-specific pathological process contributing to their disease. This approach would guide treatment to prefer using bisphosphonates, as opposed to basing pharmacologic treatment on symptoms alone.⁴
Phenotype-based treatment aims to improve clinical outcomes for individual patients, while avoiding ineffective or unsafe pharmacologic therapy.
Overall, pharmacotherapy has seen stronger integration into guideline-based recommendations since prior revisions. It is important to highlight the clinical significance of stronger recommendations for pharmacologic agents in osteoarthritis management. Due to the complex nature of the disease, having widely available and well tolerated treatment options is crucial for improved clinical outcomes. In addition to stronger recommendations for pharmacologic agents, future OA guidelines may benefit from utilization of new phenotype-driven perspectives as well.
More updates from the ACR in our 2020 Meeting Highlights