At the beginning of 2020, the ACR and the Arthritis Foundation (AF) released updated guidelines for the management of hand, hip, and knee osteoarthritis (OA) in the USA, based on the latest available evidence on the efficacy and safety profiles of various nonpharmacologic and pharmacologic interventions. Lead author Sharon Kolasinski, from the University of Pennsylvania School of Medicine in Philadelphia, talks to medwireNews about how the past 10 years of research form the basis for new strong recommendations, but also weigh against a popular treatment option.
A timely update
“We're really excited that these guidelines are out, and that there’s more conversation about how to meaningfully treat osteoarthritis,” says Kolasinski.
She notes that the ACR updates its guidelines on management for various diseases at least every 5 years, and “this was a planned update, since the last guideline [for OA] was published in 2012,” based on a literature review completed in 2009.
“Therefore, there was a decade of literature that required appropriate review,” which was a “huge task” for the team, she adds.
“I think that there has been change in the landscape and treatment of osteoarthritis in the last 10 years, and there have been important additions to the literature and […] changes in practice that were important to bring up to date.”
Kolasinski notes that “osteoarthritis is a disease that is treated by multiple modalities, as you can tell from the menu of things that we published in the guideline, so there is literature from the rheumatology, orthopedics, sports medicine, pain management, occupational therapy, and physical therapy fields [that] needed to be reviewed, synthesized, and evaluated.”
She says that the taskforce “sought a very diverse group of people to weigh in on what we should be looking at and the evaluation of the literature,” given the broad cover of specialties and range of different kinds of randomized controlled trials that were evaluated.
“So that was one of the biggest tasks, and that was the task of our literature review team, which they did really wonderfully,” she remarks.
What’s new and what’s important?
Exercise is key
A particular focus of the latest guidelines is exercise, with strong recommendations for exercise given for all types of OA covered by the guidelines
“We need to stress that [exercise] really is the cornerstone of management for osteoarthritis overall,” says Kolasinski.
She says that “the evidence continues to mount that not only is exercise helpful for patients at numerous stages of the disease, but also that multiple exercise options are available.” The guidelines state that exercise for hip and knee OA could involve walking, strengthening exercises, neuromuscular training, and aquatic activity, with current evidence suggesting no superiority of one over another.
Despite the fundamental importance of exercise in OA management, “I think that really, we have not emphasized exercise enough to our patients,” says Kolasinski, and she believes there are a number of reasons why this might be.
“Partly, we haven't had good training as physicians in how to provide an exercise prescription, but as more evidence mounts of different exercises that can be beneficial to our patients, we have a broader array of options to offer them, for things to suggest to them, and ways to approach it.”
Kolasinski says that a new approach with the current guidelines was to involve a panel of patients in evaluating the recommendations, and these people “agreed that exercise can be incredibly helpful in long-term osteoarthritis management, but getting started is often difficult,” so encouraging healthcare providers to “help patients make the transition to becoming exercisers is really important.”
Patients involved in the development of the guideline also raised the issue of OA-related pain as a potential barrier to physical activity, asking the question: “If I’m in pain, how can I exercise?”
While she feels that these concerns are “reasonable,” Kolasinski stresses that “participants in exercise trials all have pain – that’s why they're in the trial,” and “it’s important for patients to understand that, even if they’re in pain, exercise can be helpful.” She advises, however, that “what you need to do on an individual basis is assess the severity of the pain and the circumstances that provoke pain,” citing the example that if a patient has pain 24 hours a day and is being kept awake by pain, “that’s going to be a considerably different situation than a patient who has pain performing certain activities during daily life.”
She believes that for patients who experience some pain during the day, one of the best ways to get started with exercise is to begin with physical therapy under supervision.
“With one-on-one [supervision] you can be evaluated for the degree of pain that you have, as well as the movements, postures, and activities that provoke the pain, and often the patient can be instructed in exercises to stretch and strengthen that will permit them to carry out their activities of daily living with less pain,” she explains.
Rethinking hyaluronic acid injections
As well as the strong focus on exercise in the management of OA, “another point that I think is important and is a change from the previous guideline is the role of hyaluronic acid injections”, comments Kolasinski.
While the ACR’s 2012 guidelines conditionally recommended for the use of intraarticular hyaluronic acid injections, the new guidelines provide a conditional recommendation against their use in patients with knee and/or first carpometacarpal joint OA, and a strong recommendation against their use for those with hip OA.
These recommendations have changed because “the best-designed randomized controlled trials that have been published since the last guideline suggest that hyaluronic injections are equivalent to saline injections in efficacy,” she says.
Indeed, a systematic review and meta-analysis of 89 randomized controlled trials comparing hyaluronic acid with a sham procedure or a noninterventional control found that the injections were not associated with a clinically relevant benefit, but increased the risk for serious adverse events.
However, while the lack of efficacy is “an important consideration when a patient and a clinician are trying to decide how much benefit they might get from such an injection,” Kolasinski points out that “these injections have been very popular, in part, because the therapeutic options for patients who are considering them are usually limited.”
“They may or may not have been through a round of physical therapy more than once, and many of these patients are facing a decision about whether or not to proceed with surgery.
“Some of them are being confronted with the decision to try narcotic analgesics, so it’s a difficult clinical situation and patients and clinicians want other options.”
In light of these considerations, “we appreciate that this is an important area for shared decision making, but indeed, the evidence has accumulated that these injections are not as efficacious as we had hoped,” she concedes.
Upgraded recommendations
Kolasinski says that another key difference between the latest ACR–AF guidelines and the older version is that some strategies “that were previously conditionally recommended are now strongly recommended.”
Interventions with conditional recommendations in the 2012 guidelines that have now been upgraded to strong recommendations include:
- self-efficacy programs;
- self-management programs;
- tai chi;
- topical nonsteroidal anti-inflammatory drugs (NSAIDs);
- oral NSAIDs; and
- intraarticular steroids.
“Even though some of these are older interventions that have been around for a while,” the recommendations were strengthened in the latest update due to “a really comprehensive look at the literature,” comments Kolasinski. While previous guidelines were “based on a review of meta-analyses,” the current update involved “going back to the original randomized controlled trials from the inception of databases,” she says.This approach also resulted in new conditional recommendations in the updated guidelines, including for balance exercises, duloxetine, topical capsaicin for the knee, cognitive behavioral therapy, yoga for the knee, and Kinesio® taping for the base of the thumb and the knee.
The search for disease-modifying agents
While the latest recommendations provide clear guidance on many nonpharmacologic interventions and some non-disease-modifying pharmacologic options for treating OA, Kolasinski highlights the current lack of disease-modifying drug treatments.
“We all wish that there were more options that were more effective for not only treating osteoarthritis, but preventing osteoarthritis or halting its progression, and we’re just not there yet.”
Despite “an incredible amount of interest and great work that's being done all over the world, trying to identify agents that will really meaningfully treat or prevent osteoarthritis,” virtually all randomized controlled trials of potential disease-modifying agents “have been lacking in the kind of results that we'd like to see,” says Kolasinski.
She suggests that this could be explained by the complex nature of OA, and the fact that it “evolves over many years for most patients.”
“Therefore, using an agent at a point where you can effectively prevent disease, identifying what that point is, is somewhat difficult.
“You don't want to intervene too early, but you don't want to intervene too late […] and knowing when to intervene and in what way is a bit problematic.”
Kolasinski remarks that another reason why so many agents have failed to demonstrate efficacy is that OA is a disease of multiple joints, with many different kinds of tissue involved, including cartilage, bone, and supporting soft tissues. Thus, “knowing which structure to intervene on behalf of is a question as well,” and “we have not identified a single pathway” to target with drug treatments, she says.
She also highlights potential discordance between measures of disease activity and patient-reported outcomes, which is also “true in other forms of arthritis.”
“When you identify a pathway that has an impact on the pathogenesis, it may not have an impact on the patient’s symptoms,” but “in order for the agent to really be acceptable, it needs to change how patients feel and function.”
An example of this discordance is the recently published phase 2a trial of the cathepsin K inhibitor MIV-711, which did not improve the primary outcome of pain severity relative to placebo, but did reduce bone remodeling and cartilage volume loss. The investigators speculated that the 26-week follow-up period in their study may have been insufficient for the structural improvements to translate into symptomatic benefits for patients, and called for further evaluation of the agent in studies with a longer duration of follow-up.
Another agent that has shown promise as a disease-modifying OA treatment is sprifermin, a recombinant human fibroblast growth factor. The phase 2 FORWARD trial published in 2019 demonstrated significant improvements in femorotibial joint cartilage thickness over 2 years among patients treated with sprifermin versus placebo. However, the FORWARD investigators found no significant differences between the groups in terms of improvement in total WOMAC score, nor in WOMAC pain, function, or stiffness subscale scores, among participants in the sprifermin versus placebo arms.
Kolasinski says that the search for effective disease-modifying OA drugs remains “a huge interest of the osteoarthritis community,” and hopes that the coming years will see the emergence of treatment options to both modify disease progression and improve outcomes for patients.
Other research priorities
However, she believes that in the meantime, “there are many other areas of research that really would be fruitful to help our patients more immediately.”
These include establishing “what the optimal exercise prescription is for any given patient,” and which biomechanical aids and types of support could be helpful. For instance, further research is needed to determine “what footwear is best for patients with lower extremity osteoarthritis,” and “what physical modalities are helpful in hand osteoarthritis,” she adds.
Moreover, “there is a lot of interest in complementary and integrative medicine” in the OA community, she points out, noting that “patients still have a very high use and interest in a variety of interventions, including supplements, herbal products, and medical marijuana, as well as mind–body interventions, and massage therapy.”
And finally, she says that an important question to ask in future studies is: “What are the best pain-relieving agents that are available in what combination and in what sort of sequence?”
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