Chances are you’ve either personally dealt with osteoarthritis (OA) or know someone who has. This common type of degenerative joint pain represents both a heavy disease burden and a major opportunity for drug developers. Read on to learn more about:
- OA’s prevalence
- Optimal diagnostic criteria for clinical trials
- Treatment options
- What OA research looks like today
Understand the Basics
There are currently 30 million Americans living with OA. The knees are the joints most vulnerable to OA, which means that 46 percent of adults will develop OA of the knee at some point in their lives. There is currently no cure for OA, helping to make it the top cause of disability in the elderly population. Osteoarthritis is more common among women than men, especially after age 50 where it often follows menopause.
The prevalence of osteoarthritis has been climbing over the last few decades. Current research points to these three major reasons for this trend:
- Growing obesity — Extra weight puts more stress on weight-bearing joints, such as the knees and hips.
- An aging population — As people live longer, more are likely to experience conditions associated with old age.
- Increasingly sedentary lifestyles — While high-impact sports can lead to OA, staying active has a protective effect.
There are a wide range of symptoms that come with OA of the knee, but the most common criteria that drug studies include are:
- Knee pain
- Noisy, crackling joints (crepitus)
- Bony tenderness
- Bony enlargement
- No palpable warmth
- Stiffness of less than 30 minutes
- Visible osteophytes on X-rays
- Lack of rheumatoid factor and low erythrocyte sedimentation rate to rule out rheumatoid arthritis
- Changes to the synovial fluid
Of special note, the Kellgren-Lawrence (KL) radiographic grading system is especially helpful for obtaining consistent objective disease scores for use in clinical trials for OA of the knee. In this system, scores range from 0 (normal) to 4 (severe). Most studies include patients in stages 2 through 4.
Surprisingly, there is a low correlation between pain score and KL grade. At Premier, our experience has found that employing central X-ray readers leads to better consistency across study sites and reduces sources of bias that get introduced at the clinical level.
Osteoarthritis treatment modalities focus on alleviating pain and improving function. Recent efforts have also been focused on finding ways of slowing down disease progression.
Knee OA drugs in particular can be administered in a variety ways, depending on the patient’s needs and the optimal vehicle of the drug being used. The four main routes are:
- Intra-articular injection directly into the affected joint. Examples include hyaluronic acid, capsaicin, steroids, anti-TNFs, autologous platelets, and stem cells.
- Topical application to the joint. Examples include nonsteroidal anti-inflammatory drugs (NSAIDS), DMSO, and capsaicin.
- Taken orally. Examples include NSAIDs, COX-2 inhibitors, opioids, SNRIs, glucosamine/chondroitin, and tramadol.
- Subcutaneous and intravenous injections. This is the main route of cutting-edge biologics, including anti-NGFs, anti-TNFs, and other disease-modifying antirheumatic drugs.
Considerations for Osteoarthritis Clinical Trials
There are three main treatment objectives when it comes to OA drug trials: chronic pain management, treatment of other OA signs and symptoms, and disease modification. When evaluating these, the knee model is relatively easy to work with, as this joint is simple to visualize and reach with topical and injectable drugs. For pain trials, study designers should take into account the high placebo effect for such treatments and incorporate methods of mitigating this issue. (For more placebo effect info, have a look at our Placebo Problem series in progress, beginning with Part 1.)
There are 210 interventional studies currently planned, ongoing, or temporarily suspended — and that’s not including historical or epidemiological studies! Of these interventional studies, two-thirds are in phase 2, while the remaining third is in phase 3. Additionally, more OA studies are being conducted in the U.S. than in any other country, representing only roughly 25 percent of all ongoing studies. The competitive landscape of OA research is a global one.
These factors may make OA sound like a crowded field, but it’s one with a global patient base large enough to support it. If you’d like to know more about the unique challenges — and solutions! — of OA drug development, check out our latest webinar, Chronic Pain: Conducting Clinical Trials in Osteoarthritis.