Lisa Mandl, MD, on Therapeutic Targets in Osteoarthritis Management

Over time, management strategies for osteoarthritis (OA) have shifted from traditional approaches of focusing only on pain control to interventions which also focus on improving functional activity and quality of life. Current optimal management strategies include nonpharmacologic and pharmacologic approaches that focus on the prevention of disease and progression, not just palliation of disease.

Pain control also remains an important clinical challenge in the management of OA.

Rheumatology Consultant caught up with Lisa Mandl, MD, MPH, from Hospital for Special Surgery, about the goals of OA management, therapeutic targets essential in the management of OA-related pain, other potential therapeutic targets, and more.

Rheumatology Consultant: What do you think is the most important goal in OA management?

Lisa Mandl: In 2019, the main goal is to improve mobility. Treating a patient’s pain is of course important, because patients and physicians worry a lot about it, but in the big picture, we want patients to get back to being as functional as possible. To do this, the first thing is to address the nonpharmacologic components available for use, such as physical therapy and modalities like tai chi or yoga. Rheumatologists should also consider alternative therapies which might align with their patients’ preferences, such as acupuncture. We have to be engaged with our patients and partner with them to find the best nonpharmacologic plan. This is the most important thing we can start with our patients, and I think it is forgotten sometimes.

RHEUM CON: What are some of the potential therapeutic targets for improving pain in OA?

LM: There is a lot of important research going on right now. Some of the most exciting targets being looked at include nerve growth factor (NGF) and a new injectable formulation of corticosteroid. This formulation hangs around the joint much longer than regular steroids, so it may help decrease pain longer without having to give repeated steroids, which can hurt cartilage. These agents are not quite ready for prime time, but there should be more data very soon. Other options that are getting a lot of press are platelet‑rich plasma and stem cells. I would not recommend these until there are more stringent and rigorous studies performed, as neither have been proven effective for OA.

RHEUM CON: Which therapeutic targets do you think are most promising?

LM: NGF is a promising therapeutic target for the treatment of OA pain. NGF is a neurotrophin that is released from inflamed tissue and sensitizes peripheral nociceptors. Clinical trials of tanezumab, a humanized monoclonal antibody against NGF, showed significant reduction in pain and improvement in function among patients with knee OA. This is very exciting and encouraging, but NGFs are still evolving. NGF has also had a history of possibly accelerating destruction of the joint, so this issue needs to be re-explored. I think it is too early to talk to our patients about stem cells and platelet‑rich plasma. I will be excited to see findings from ongoing studies in this area. Right now, it is hard to know if they are going to work or not for our patients.

RHEUM CON: Most research on therapeutic targets have focused on articular cartilage. What other elements should be considered to understand OA and optimize management?

LM: OA is not just a disease of the cartilage, but a whole joint disease. We know the cartilage is affected, but the cartilage does not have pain fibers. The pain a patient feels comes from the other tissues. The subchondral bone is affected, as well as ligaments and tendons. Therefore, it is important for patients to engage in physical therapy because the muscles that surround the knee joint can act like a splint and help stabilize their joint. This allows for less pain when a patient moves. We have to remember that all components of the joints are important, not just the cartilage.

RHEUM CON: What is important for a rheumatologist to remember to optimize OA management?

LM: OA management needs to include a combination of nonpharmacologic and pharmacologic strategies. Nonpharmacologic strategies are useful and can help reverse pain. This needs to be emphasized because a pill or injection is not necessarily going to fix everything, especially if you do not have a multipronged approach. It is also important to remember that repeated intra‑articular corticosteroid injections can be detrimental to the cartilage. However, the occasional steroid injection can be extremely helpful for patients who have a flare. We should keep the occasional injection in our back pocket for patients, but if you are giving a patient constant steroid injections, this should be a red flag that something different is needed. It is also crucial to know the difference between nociceptive pain—pain coming directly from the joint—and pain related to central sensitization, which is when minor stimuli feel disproportionally painful, usually due to the way the brain and central nervous system is processing pain. Knowing what kind of pain you have can make difference since the treatments can be different. It is also important for rheumatologists to remember that joint replacements can be extremely effective for the right patient. It can take patients, especially women, a long time to decide if this operation is right for them. It is often helpful to let patients know that a joint replacement is a potential therapeutic option earlier rather than later so patients are aware this could be something down the road if they ever need it. Having this knowledge can also help them contemplate the pros and cons before they have end-stage disease.

Lisa Mandl, MD, MPH, is a rheumatologist at Hospital for Special Surgery in New York City.

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