Expert opinion

Serge Perrot is a rheumatologist, pain specialist and Professor at the Paris University. Philip Conaghan is Professor of musculoskeletal medicine and Director of the Leeds Institute for Rheumatic and Musculoskeletal Medicine at the University of Leeds; Anne-Marie Malfait is Professor in the Department of Internal Medicine at Rush University, Chicago where she is also a researcher.

The faculty stress the importance of realising that pain is an experience different for each patient, and loss of function, difficulty sleeping and quality of life (QoL) impairment are just as important as the pain itself. Complete ablation of pain is unrealistic so there is a need to tailor expectations for patients and try to help them return to a normal life as much as possible.

Pain assessment

In order to help people, physicians need to understand their pain. Professor Perrot describes the importance of considering the evolution, type and quality of pain in order to adapt treatment. Professor Malfait confirms that it is not enough to just measure pain intensity, and while pain can be quantitated by sensory testing, we are unable currently to identify particular pain mechanisms in our patients.

Risk/benefit considerations

Everything done for patients has potential benefits and risks. Professor Conaghan describes how we are not very good at predicting which subsets of patients will respond to the two most common pharmacological therapies, NSAIDs and weak opioids, and that side effects often occur earlier than potential benefits. Professor Perrot urges us to regard treatment benefits in line with the aims of management, which should be to improve function, and highlights that the only way to tell if a treatment is working is to ask the patient.

Find out more about individual goal setting for patients.

Professor Conaghan makes the point that we now have more guidelines than therapies. Recent guideline updates address the treatment needs of OA in different joints and multiple sites and continue to recommend a holistic approach using pharmacological and non-pharmacological therapies. Professor Perrot comments that the efficacy of the guidelines could be improved by adapting them for the different physicians that might use them, for example, primary care physicians, rheumatologists, orthopaedic surgeons and physical therapists.

Need reminding of the available guidelines? Visit the clinical guidelines section for an overview.

Exercise – friend or foe?

Professor Walsh and the faculty discuss that while all the guidelines for OA encourage exercise, patients often are not keen to exercise because it hurts. Professor Conaghan describes the plentiful clinical trial data that support that muscle strengthening over a period of weeks reduces pain, despite short-term aggravation. Informing patients that they won’t further damage their joints by exercising is important and Professor Perrot advises that pre-emptive analgesic medicine to use before exercising can work well. Professor Malfait also discusses the benefit of combining exercise with weight loss for patients with OA.

Drug combinations

Professor Walsh queries whether physicians should choose between treatments or combine them. Professor Perrot comments that, often, patients try one treatment and when that fails they move to another. This is not optimal as there are different types of pain, which means that combining treatments in a mechanistic approach can improve pain throughout the day. However, Professor Walsh comments that combining treatments will also lead to more side effects. Professor Conaghan comments that while there is often a reluctance from patients and physicians to discontinue treatments even if they are only giving a small benefit, regularly reviewing and rationalising treatments is important.

Misconceptions

Professor Walsh asks the faculty questions about the common misconceptions when treating OA pain. There are two main misconceptions:

• Pain is related to the joint damage
• Analgesics mask pain that is useful to avoid further joint damage

Professor Perrot comments that there is no strict correlation between intense pain and severe OA and that pain should always be treated. It is important to discuss these misconceptions with patients to ensure treatment adherence. Professor Conaghan highlights that the second misconception is a much smaller issue in clinical practice but community education about the different types of pain and when it is safe to do muscle function exercise and physical therapy is important, given it is so effective and without side effects.

Professor Malfait comments that while the ‘holy grail’ for OA is a treatment that targets both joint damage and pain, current research into the mechanisms of OA pain has identified different potential strategies for treating pain, which is exciting, given that physicians have been using existing treatments for a long time. There is considerable evidence that OA pain has a strong peripheral drive and that targeting the neurotrophin nerve growth factor (NGF), an important pain mediator in the periphery, has proved successful, with several clinical programmes for neutralising NGF antibodies at quite advanced stages.

Anti-NGF antibodies and joint damage

Professor Walsh queries the uncommon problem of NGF blockade causing serious increases in joint damage seen during clinical trials. Professor Conaghan responds that while we don’t fully understand rapid OA progression, there is evidence that it is associated with increasing doses of anti-NGF antibodies and concomitant NSAID therapy.

For example, in Study 1043 32 of the 34 patients that required total joint replacement took NSAIDs at some time while they were treated with tanezumab¹. Note that since the recording of this video, the tanezumab program has been discontinued.

Similarly, a phase IIb/III study reported treatment emergent adverse event rates of 17% with fasinumab and 10% with placebo. Adjudicated arthropathies occurred at a higher rate with fasinumab, compared with placebo. This was clearly dose-dependent and dominated by joint space narrowing (RPOA-1). Most patients were not symptomatic and there were no cases of osteonecrosis. Rates of joint replacement were found to be similar across treatment arms².

Professor Malfait highlights that while this rapidly progressive OA is only seen in a small percentage of patients treated with an anti-NGF antibody, it provides an opportunity to better understand the relationship between joint damage and pain.

Want to see the clinical data? Visit the emerging therapies section for all the details.

How important is pain relief?

Professor Walsh poses the question of how bad a side effect needs to be for a patient not to want effective pain relief. Professor Perrot comments that if you only look at the side effects, there are many patients who just could not be treated and so individualising treatments involves looking at both efficacy and side effects, which can often be managed. Professor Conaghan highlights that despite new treatments on the horizon, they will not replace the need for exercise-based therapies.

• Be ambitious for your patients – consider not only pain, but loss of function, difficulty sleeping and quality of life for every patient
• Really listen to your patients – only they can tell us if a treatment is working, we can only predict what might work
• Remember that NSAIDs have a different time course for toxicity and efficacy – many patients stop taking them before they have had the opportunity to have an effect
• Regarding treatments, bear in mind that there is a considerable placebo effect, and conversely a nocebo effect in patients with OA pain
• Consider that new effective pain treatments are not going to restore function if patients already have wasted muscles – exercise and physical therapy is always going to be hugely important

More on emerging therapies