As the be dreaded Corona virus continues to spread and I read just today that there are chances that the virus can spread between people that don't even have any symptoms yet (making it very hard to track), it's obviously a 'serious' condition sometimes resulting in death.
We too have a condition that may be deemed by the FDA and TGA as 'serious' that we address, namely OA. Tonight I cover the seriousness of OA. Don't be fooled, OA is not 'just' pain, there are other repercussions, read on...
INTRODUCTION
Back on December the 1st, 2016 a report was presented to the FDA by Oarsi to highlight the condition of OA and the current std of care and why the FDA need to address OA as a serious condition.
OARSI White paper submitted to FDA
WHO IS OARSI
They stand for Osteo Arhtiritis Research Society International and basically are dedicated to advancing the research and understanding and of course treatment and prevention of the disease. It's a non profit organisation. They host an annual world congress and produce a peer reviewed journal.
I will summarise this report for you but certainly if you have time it's an interesting read. Do enjoy:
Probably the main and first quote I need to extract for you is this one that summarises the entire report:"OA has all the hallmarks of a serious condition". The report goes on to say that it is not just a single problem that OA causes but it is a thing called co-morbidity, "severe with chronic pain, progressive irreversible structural damage and progressive loss of function, often with associated decline in mental health as well as an increase in mortality when a person is no longer able to walk or live independently. Pain from arthritis is one of the key barriers to maintaining physical activity and can be considered a key factor in onset of frailty in the elderly ".
NSAIDS are commonly prescribed to tackle OA but these have nasty side effects as the report indicates:
"Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with a clinically relevant 50 –100% increase in the risk of myocardial infarction or cardiovascular death compared with placebo".
Did you read that properly? A 50 - 100% increase of heart failure.
"As many as 20-30% continue to experience pain and disability after total joint replacements and one in five require joint replacement in another joint within two years".
As we have discussed in the past here at HC, there is potential for iPPS to act on patients post surgery.
"The more severe the walking disability, the higher was the risk of death (p value for trend <0.001), largely due to cardiovasular disease".
So how does OA start, how does it progress?Well the report describes this for us in words but I thought I'd put it into a flowchart for easy readability:
Typically how OA progresses and what it means to the average patient.
HOW IS OA PROGRESSION ACCELERATED?
OA progresses at varying rates but will progress in all people. "People who have OA in multiple joints, have a strong family history, are overweight, work in load bearing occupations or with repeated joint injury, progress at a faster rate. Within the US, the prevalence of doctor-diagnosed arthritis, which includes OA, is expected to increase in the coming decades".
"By the year 2030, an estimated 67 million adults (25% of the projected total adult population) aged 18 years and older will have doctor-diagnosed arthritis, compared with the 52.5 million adults in 2010-2012." The problem is it's a vicious cycle: "Both within the US and Europe, adults with OA are significantly less likely to meet the recommended levels of physical activity compared to adults without OA. After lifestyle factors, this could also be explained by the fact that people with OA tend to avoid physical activity because activity induces pain. However, decreased physical activity levels might lead to decreased muscle strength and stability of joints, which have been shown to be important risk factors for the onset and the course of OA".
The ironic part: 'While low physical activity is a problem globally, over the past few decades there has been an increase in participation in both youth sports and recreational activity among all ages. This has resulted in an increase in both acute and chronic musculoskeletal injuries, with joint injury being the most common risk factor for OA development in young adults 36. As life expectancy continues to increase, the span over which adults participate in such physical activities is also increasing. Therefore, the incidence of knee injuries among older adults can also be expected to increase' 3 . So let me surmise, we are living longer so there are more cases of OA. But we are being told to exercise more at a younger age which we are doing in greater numbers as youths and this is causing an increase of OA at younger ages due to an increase in sporting injuries! It's like we are burning the candle from both ends and it's all leading to sharp increases in OA affected patients both younger and certainly older.
Take a look at the following figure again from the same OARSI report. (If it's a bit unclear/small try double clicking the image to enlarge or alternatively follow above link to the report to see it in full detail for yourself).
Figure 1 Ranked conditions of Year's life lost due to disabilities.
Yes Osteoarthritis is increasing but look at other related indications such as Lower Back Pain (Rank 1 by all measures for both sets of years). COPD also features in US, how is that related to us? New guys, see my post which covers COPD, a little about what it is and how we may address it one day in the future: https://hotcopper.com.au/threads/par-copd.4822883/
Other Musculosketal ranks at #2 and neck pain is up there too.This data does NOT include OA of other joints such as hands, feet, elbows etc.
OA - A SERIOUS CONDITION?
Adding to the Serious condition: "The impact of arthritis on individuals is significant. Globally, 80% of those with OA will have limitations in movement, and 25% cannot perform their major daily activities of life" 3. "Eleven percent of adults with knee OA need help with personal care and 14% require help with routine needs Strong relationship between ability to walk".
Death in regards to OA:"Walking disability was a significant predictor of survival in OA – the more severe the walking disability, the higher the risk of death". Serious? Death? I would say so.
OSTEOARTHRITIS IS ASSOCIATED WITH PERSONAL AND SOCIETAL ECONOMIC LOSS
How about a stat that involves Aus. again quoting from the report: "Within Australia, the median total accrued personal savings by the age of 65 years of males aged 45-54 who retired early from the work force due to arthritis (not specifically OA), was estimated to be as little as AU$315. This is considerably less than the median accrued personal savings for those who remained in the workforce full time, whose estimated personal savings at age 65 years was AU$339,121133. The median weekly income of those who retired early due to arthritis (not specifically OA) was AU$260, compared with those employed full time who were likely to earn on average five times this amount"
From insurers point of view, hospitalisation's due to OA is much greater, back in 2005 the direct aggregate annual medical costs for OA was some $185.5 Billion. :See fig 2 below.
Figure 2 = Back in 2010, OA features heavily in hospitalisations. It's a costly burden to both Public and Private systems.
On Page 40 of the Oarsi report the author's write this statement "There is, however, no evidence for any agent consistently providing clinically and statistically significant slowing of progression of OA.". Finally there is could be an 'agent', iPPS.
MOZZARC, WHY IN YOUR OPINION WILL WE BE SUCCESSFUL ?
The report goes on to compare current remedies namely: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo "treatments may be effective for reducing pain, long-term data is lacking and safety data is inadequate. Again it should be noted that these treatments are for the reduction of symptoms, and do not provide a cure for OA. "Treatments are needed that alter the natural history of increasing joint damage, and could possibly increase cartilage, decrease bone marrow lesions and robustly reduce inflammation associated with OA". As we know, not only do they give a milder form of pain remedy compared to us BUT they have no effect on Cartilage wearing our further and IN FACT some of them ADD to the rate of destruction.
On top of that, as if that's not simply enough, there are a number of Adverse effects mainly with NSAIDS.
NSAIDS
The report goes on to state to the FDA, NSAIDS results in "twofold to fourfold increases in the risk of myocardial infarction, stroke, or cardiovascular death compared with placebo ". PAR being Successful will be a gross understatement just in my opinion, yes we may take a little while to start up but , and I apologise for this untimely comparison, we will catch on like wild fire.Yes of course we need to pass the Third Phase trial and there may be hurdles and delays, keep this is mind, but if when we get through...well just wait for it, it's gonna be big (my views) ...
RISKS OF NSAIDS
I actually could prob do a separate post entirely on this but here are some risks of this current so called std of care:
The increased risk of peptic ulcer bleeding by taking these NSAID's...let's turn this into a quiz..
A) 2% more
B) 30% more chance
C) 100% more
D) 110% more
Yes of course it's more than any of those answers above, it's a Mozzarc quiz ain't it? ... 450% is the answer.As many as 25% of chronic NSAID users will develop ulcer disease, gastrointestinal hemorrhage, perforation and ulcer disease due to NSAIDs.
NSAID has been "...reported in more than 100,000 hospital admissions annually in the US and between 7,000 and 10,000 deaths, especially among those who have been designated as being in a high-risk category". There is strong evidence for a link between using this stuff and Death from Cardiovasular disease. The same link exists with NSAIDS and Atrial Fibrillation.
There is also discussion of Chronic Kidney Disease - An increase in risk of this with use of NSAIDS.The report then goes on to contrast NSAIDS with Opioids and it finds that Opioids may actually be even more harmful. "A meta-analysis of studies of opioids in OA showed that while there may be a small benefit in pain reduction from treatment with opioids, this is outweighed by significant increases in risk of adverse events "
OK OK pause..I just learnt something tonight that i didn't know...have you guys heard of Voltaren? Yeah its common and can be found everywhere and every pharmacy in Aus. Hmm I have always thought it was some innocent Panadaol kinda thing..nope, it's a NSAID as well.
Huh? This is a NSAID? Did you know that? I didn't!
Want another mind blowing fact on NSAID's? In 2014 what percentage of the US army was on NSAID'S? Quiz time? Sure:
A) 0.03%
B) 1.45%
C) 2.1%
Yeah you are right..it's more than 5%....want the figure?
82% 2 That wasn't a typo...Ok I'm on a role now...here is one more factoid/Mozz Question; How many doses worldwide each year are consumed of those awful NSAID's?
A) A lot
B) Ten Million doses
C) Twenty five Million doses
Well if you said it's another Mozz quiz and the answer is either A) or something more than C) you'd be quite right and you'd be learning from my past quiz's...
The answer is an astounding 30 Billion.3 (Yes this fact is from a Harvard Medical school source)Now I agree, there ain't many alternatives our there and used sparingly, it does give some relief and is madly popular and highly prescribed. All I'm inferring is that a viable and better alternative is on its way to you soon...yeah, iPPS (you are the owner of this amazing product, remember? Whaddya mean you aren't a shareholder and are waiting for the right time to buy?? Ok Ok that was aimed at the new guys [specially those Basement Trolls I'm expecting any day now - Thanks HeyItsJay])...
Now can you understand why I think we might have a large market? Yes Yes I know we aren't going to take over the entire market but what I AM saying is the OA and Pain markets are vast and we have a real shot of capturing even 1 or 2% of it and that will be compelling let me tell you. (My opinions here).
It's not just about VOLUME and MARKET SIZE..it's about being a DECENT and SAFE option... an actual viable alternative compared to the current std of care. This is my point. Market size and volumes will come (My views).
Back to the report, as a final treatment Joint replacement is covered but the report documents that it is certainly not considered to be a cure and that greater than one in ten patients still continue to experience pain in the replaced joint.One of the key goals of the paper is stated on Page 44 (I've bolded for emphasis): "The goal of this white paper was to demonstrate that many patients with OA clearly suffer from a serious disease, and the progressive disability observed in these patients is associated with reduced mobility and increased risk for death. Both of these findings fulfill the FDA definition of a serious disease". It is here Paradigmers that I'm sure the FDA (and TGA) would classify OA as a serious disease and it is this designation that I believe will help us immensely in a major way in pursuit of clearing the important Phase 3 trial."With the global impact of OA constituting a major challenge for health systems in the twenty-first century and in the coming years, the importance of having therapies available to stop the disease progression and to manage the symptoms (e.g. pain) needs to be a priority".
I have little doubt the FDA know how serious OA is, it's effects and damage it's doing not only to the individual but to society too. I'm personally buoyed by the fact that we have the great Dr Felson working with us to show them (FDA) what exactly is the mechanism of action and how we can address all the nasties presented by such reports as this one back in 2016. This is happening in JUST 18 days Paradigmers.
DISCLAIMERS
Yeah there are some positive and certainly enthusiastic type statements here, please don't think I'm a crazy up ramper. I'm just telling you to consider the facts...yes there are some negatives though I think they are minor and don't hold a candle to the positives. Do your own research is always the best policy...debate it...rationalise it...don't just listen to one source (me). Read widely and discover what we have and what we are about, for yourself. I certainly did and I liked what I saw.
... 450% is the answer.As many as 25% of chronic NSAID users will develop ulcer disease, gastrointestinal hemorrhage, perforation and ulcer disease due to NSAIDs.
(20min delay)