The patients who will benefit from a novel treatment for knee osteoarthritis

Dr Jonathan Rees is a highly experienced consultant rheumatologist and sports physician. Having trained at several London teaching hospitals, he has previously worked as a consultant at the Defence Medical Rehabilitation Centre Headley Court, acted as the Honorary Consultant Rheumatologist at Guys’ and St Thomas’ Hospitals, and been Consultant Rheumatologist at Addenbrooke’s Hospital in Cambridge. Dr Rees now works privately at Fortius Clinic in London and in Cambridge, treating conditions including osteoarthritis, rheumatoid arthritis, gout, back pain and osteoporosis.

In this article, Dr Rees examines the treatment options currently available to patients with osteoarthritis and introduces Arthrosamid^®, an intra-articular polyacrylamide hydrogel injection (iPAAG) that works to cushion the knee joint and relieve pain in those suffering with knee osteoarthritis. He goes on to detail the types of patients he believes will benefit from Arthrosamid^® — explaining why this novel treatment could become a key weapon in clinicians’ fight against the disease.

Osteoarthritis (OA) is a progressive, irreversible process leading to cartilage – and joint – damage. The most common musculoskeletal condition, OA poses an enormous burden on health and social care provision in the UK, with an estimated 1 in 5 adults over the age of 45 suffering with OA of the knee and 1 in 9 adults with OA of the hip.¹ It adversely affects patient’s quality of life and, potentially, their quantity of life.

OA in some patients appears to be genetically driven and can run in families; this is known as primary osteoarthritis. Secondary osteoarthritis occurs when cartilage is damaged by events such as injury or other medical conditions. These include obesity, biomechanical problems, and rheumatoid arthritis. As we live longer, the prevalence of OA rises. The knee is a highly complex joint which is frequently injured and prone to OA.

Treatment for OA can be categorised into three core groups; conservative treatment, medical treatment — which would include injections — and surgery. Unfortunately, we do not currently have any treatment that can modify the disease process itself, thus OA remains a progressive and incurable condition (unlike conditions such as rheumatoid arthritis which have numerous medications that can halt or arrest further joint damage).

Conservative treatment for OA includes weight management and patient education. Conservative intervention might see the patient wearing cushioned footwear, or orthotics and bracing. Another such intervention is to help patients become stronger and fitter through physiotherapy and conditioning exercises. 

After conservative treatments, the next step in the treatment pathway is often oral medication (analgesia). Medication such as paracetamol, anti-inflammatories or codeine are commonly used. Medications including duloxetine may be offered as a second-line agent. Unfortunately, each medication has potential side effects, and the effectiveness of medications are very variable. Some medications may be used topically, such as anti-inflammatory agents or capsacian. There is some evidence that TENS machines (transcutaneous electrical nerve stimulation) can also provide some benefit in OA.

If oral or topical medication is ineffective (or inadvisable) then injection therapy may be offered. The most commonly offered injections are cortisone based. Cortisone is generally quite helpful for a flare up and often improves swelling, pain and function in the short to medium term. When cortisone works well, it can provide a period of pain-free (or pain-reduced) time where the patient can rehabilitate more effectively and become stronger. The duration of benefit can be highly variable and there are potential side effects, including lack of benefit or worsening of symptoms, cartilage degradation and the rare risk of infection.

Knee joint injection with hyaluronic acid (HA) is another option. HA is a normal component in healthy knees and injecting the knee with exogenous HA (HA made outside the body) has been shown in some studies to reduce pain and improve knee function. HA injections are usually well tolerated; however, benefits can be relatively mild and HA injections are not recommended in the UK as being cost-effective for the NHS by NICE.

Other ‘niche’ techniques have been used, in particular platelet-rich plasma (PRP) as an injectable. There is evidence that PRP may be effective in some patients. Further work in this field is ongoing to determine potential optimal dose and type of PRP. This option is not currently widely available.

In addition to the physical limitations of knee OA, there are significant psychological implications. Indeed, the psychological aspects can be as important — and difficult — to deal with as the physical. As a sports doctor, I see many injured athletes of all ages for whom sport is a central part of their identity. If you take the ability to run or play their sport away from them, the psychological impact can be severe. More generally, most people enjoy being active and if they can't go up and down the stairs at home or at work, they can’t walk to a bus stop, or they can’t actively play with their children, this will also have a detrimental effect psychologically.

Common surgical techniques for knee OA have included ‘wash-out’, realignment (altering the biomechanics of the knee) or partial / complete joint replacement. Wash out was previously a common treatment for OA in the UK, involving arthroscopic (keyhole) surgery to clean out any debris inside the knee. However, recent evidence suggests it is ineffective for generalised knee OA. Realignment procedures (such as a tibial osteotomy) can improve the function of the knee for some patients with OA in specific areas of the knee. However, for many patients with advanced knee OA, total knee replacement (TKR) is the only viable surgical option.

For patients in whom pain is severe and physical demands on the knee are not high, TKR can produce high levels of patient satisfaction. However, for the younger and generally more active patients, the physical limitations of a replaced knee are a major issue. Joint replacement is, of course, major surgery.

Knees are not simple joints to replace. If we compare knees to hips, the hip is a ball and socket joint and, in general, a replaced hip more closely matches the function of the original joint than a replaced knee. Generally, a replaced knee (modified hinge joint) is more difficult to match the function of the original joint. As a replaced knee joint won’t be as functional as the original knee, you ideally want to avoid your OA patients having a knee replacement before they are at least 60 years old, as joint replacement in younger patients greatly increases the chance of an early revision (re-do replacement). Revision surgery can be challenging, does not generally yield functional results as good as the first replacement, and comes with a risk to both mobility and the limb in the future.

There are a significant number of OA patients on waiting lists for knee surgery, possibly having already been waiting for a year or more. This wait has been worsened by the COVID-19 pandemic. Increased waiting time is likely to have a negative effect both physically and psychologically. Reduced physical conditioning pre-surgery increases the risk of surgical complications.

Which brings us to Arthrosamid^®. I believe there are three types of OA patients who will be suitable for a non-biodegradable, single-dose injection and who might find this treatment beneficial. Firstly, there are those active potentially younger patients who might want to postpone (or avoid) a TKR. If we, as clinicians, can provide sustained pain relief and get a patient to 60 before a knee replacement, then they will have more years with a functional knee and they also get the benefit that the replaced knee will not have to last as long — thus reducing the possibility of requiring revision surgery.

Secondly, there are patients who require TKR and are on a waiting list for surgery. If they had access to an Arthrosamid^® injection, this could well give them a year or two of pain relief benefit so they could more easily stay fit, have a better quality of life, and be a better surgical candidate when the time comes for their replacement.

Thirdly, there are those advanced OA patients for whom a replacement is not viable and who are not suitable candidates for surgery; perhaps they have a poor anaesthetic risk, or they have medical comorbidities. They’ve exhausted all available treatment options and they’re looking for something else to help reduce their knee pain. Despite the options available to us as clinicians, it is evident that there are OA patients for whom standard treatments are ineffective — and whom Arthrosamid^®could help.

Arthrosamid^® is unique amongst current treatment options in terms of the long-term and sustained benefits it provides OA patients. It provides cushioning to the knees that is more permanent than what is currently available. That said, this is a novel treatment and, inevitably, there will be concerns about what it does to your body. A prudent practitioner will only use a new treatment when there's no other option — and typically in those patients displaying the worst symptoms. I anticipate that we will use Arthrosamid® in those OA patients who have had education, analgesia, and physiotherapy, they've done what they can to control their weight, and they’ve either had, considered or can't have a cortisone or a viscosupplement injection, and have considered PRP. As we wait to learn more about the safety profile of this medical device, you would expect a clinician to have administered other treatments before they opt for Arthrosamid^®. Of course, no treatment is without risk and benefit so side effects and available data should always be reviewed — but Arthrosamid^® shows promise.

There is a definite treatment escalation in knee OA, with conservative, medical, and surgical options available. Arthrosamid^® provides a bridge between medical intervention and surgery — allowing us clinicians to potentially either delay or avoid TKR for our OA patients. My view is that Arthrosamid^® fills an obvious gap within current treatment options and offers certain groups of patients an effective alternative to the currently available therapies. It is a definite case of right patient, right place, right treatment.

^References:

^{1. Arthritis Research UK - Prevalence of osteoarthritis in England and local authorities: Birmingham}

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