War On RA - Part 3- Useless Drugs Save

This is the War on RRA. Useless drugs. Useless drugs? Hell, drugs are the best thing we've got. Drugs are all we've got in managing RA.

What's he talking about? Well, we have this strong reliance on drugs and that's what I want to discuss in this particular edition of the War on RA. You know, in 1998, I believe, Jim Fries from Stanford did a study, a survey actually of US rheumatologists and asked them what the milestones were in RA care. I know the results of that study and so I repeated it in 2008 and the comparisons are interesting. They looked at a lot of different diseases, but in RA in 1998, the major advances that you chose was early aggressive therapy and combination therapy and then third or fourth down the line was methotrexate.

By 2008, this had changed. TNF inhibitors were at the top of the list. Next was early aggressive therapy, combo therapy methotrexate, and fifth or sixth down the list were other biologics. If we repeated this today, I think we would say drugs, drugs, drugs and all the new drugs that we have. Nowhere on this list was a discussion of the pathogenesis of the disease, you know, CCP, the shared epitope, things that clearly are underlying what's going on.

When asked what was most disappointing in 2008, you said the cost of care, managed care, lack of timely referral, lack of a cure, and no known etiology. I think your hearts are in the right place. The question is, what are we doing about that? What would today's survey look like? I think it would be very focused on drugs.

We have lots of options. In rheumatology alone, we have 28 biologics. 19 of them were actually approved for rheumatoid arthritis in the last twenty years. Of the 19, however, 15 are biosimilars or me too copies. We have five TNF inhibitors, for instance.

And does that really change the field? Does that change the paradigm? Does that change our patient's chances of remission, winning the battle so we can win the war? We have two JAK inhibitors and by the end of the year, we're gonna have three or four and are they gonna change the game? The facts are the following.

The next best prescription you write for a rheumatoid arthritis patient is going to have a thirty to fifty percent chance of failing. And if it does succeed, more than half of them are not going to be on the drug two years later. Of the fifteen to thirty five percent who will stop the drug for toxicity realize it's going to forever scar the psyche of the patient who's now worried about the next drug that you're going to prescribe to them. This is a problem. What we really need is the right drug at the right time.

And like the proverbial thermos, how will we know? Ask your friends. Many of you think that drugs are the answer, but you know, it's just the new kid in town and how does that usually work out for the new kid in town? I think it could be that we're all just guessing. People don't like when I say that because we're smart, we know what we're doing, we're usually successful.

But if we're not guessing, then why are all the clinical trials with our best new drugs essentially non inferior to each other. They're equivalent. They're all hitting the sixtyforty benchmarks in the same manner. There's no new advantage to any of the new drugs that we've seen in the last ten years, maybe even twenty years. The major differences between the drugs we currently have is, is it a pill or a shot?

And really what I'm saying here, will the patient accept your recommendation and buy into it? Is it the marketing and the name recognition? Clearly that's important in what drives the market and what people are going to use. Is it going to be your familiarity of the drug? Did you do the clinical trials?

Did you attend a conference where you heard about all the data? But the problem is we tend to rely on the data we know best, the experience we know best and why we use the old drugs preferentially over the new drugs. And which one is preferred or forced to you or forced upon you by managed care and insurance companies? Does that drive you crazy or what? Managed care?

You mean the industry that we trust our patients welfare to the one that is driven by billions of dollars in income and millions of dollars in bonuses for the individuals who pave the way and the choices that are preferred or who established the tiered therapies approach. You mean the industry that has GED knuckleheads wasting my staff's time trying to get prior authorization when they're trying to help patients, but instead they're wasting time waiting on the phone to deal with people who are really looking at an algorithm on what their choices are. Wait, let's not even call it an algorithm. It's really a Crayola list of two or three drugs, not very intelligent. It's driven by the monies, the rebates, etc.

What I call kickbacks. The industry that forces upon me to them trying when I'm trying to go to bat for my patients to talk to a dyslexic physiatrist who knows nothing of RA, who can't spell canakinumab and has no idea what we're talking about, but is really trying to read off a script and trying to obstruct what we think is good care. I know it's very maddening and it gets in the way, but still the facts are your management is usually very successful in many people. It's strongly rooted in knowledge, experience, and the utmost of care and interest in patient welfare. However, our best therapeutic choices are either an educated guess or at worst therapeutic adventurism.

It's only going to be confounded by the idiocy and greed of insurance companies and managed care, uncomplicated even worse by patients who may not trust you, have uncertainty over that which you prescribe. It's a really complex story. But again, your role in management is what's going to guide this, not necessarily the drugs. If I'm correct in saying it's a toss-up, it's a toss-up between whether the next best prescription for this patient is Orencia or Enbrel, then managed care is probably okay in saying it doesn't really matter and hence let's make the choices based on financial gain, our financial gain, not financial gain that benefits the patient and certainly not the physician. Instead, why are we not making other decisions, these decisions not based on money but instead based on data, either new data or big data or something that gives us a 10%, 15% advantage.

Today in RheumNow, we published a report from the Swedish registry looking at which is the best biologic when you got to use biologics beyond TNF. It's an eye opening report because it shows in real world experience that when choosing the first biologic or a switch biologic, non TNF biologics, especially rituximab and tocilizumab fared better than the TNF inhibitor. Again, that's first biologic or second biologic. And the differences here were 10 to 25%. They're not small.

If I told you the next biologic that you wanted to use was wrong, the one I wanted to use was gonna be better because it was 10 to 20% better, I think you'd go along with me. We need that kind of advantage. You know, there are reports out there about when choosing biologics, if you made your choice based on whether the patient was strongly seropositive or not, you might do 10% better in choosing abatacept or rituximab. Again, that's under certain situations, but we need that kind of advantage to benefit our patient. You know, life has been good for many of our patients and that's mainly your fault, your role, your expertise.

But again, we need great advances in RA to do better than we've done. And these haven't yet come. What is the next milestone? I think it's from better science, smarter management, maybe driven by data and not necessarily the new drugs. Where are new drugs important?

Well, they can be important if they change the paradigm and how we use them. You know, it's sort of an example of Tipping Point, the great book by Malcolm Gladwell that talked about the sociology of change. If you look at the statins for instance, it's a really interesting story. The very first statin which came out I think in the seventies was lovastatin, Mevacor. Many of you have never even heard of that drug because no one used Actually it took two, three, four, the fifth statin Lipitor to change the market.

So in this case it was new drug introduction, so a succession of new drugs. It was time and the time necessary to show that these statins, this intervention led to not just improvement in the primary endpoint, which is what your cholesterol level was or your LDL level, but instead the major improvements, the big time improvements, death, hospitalization, surgery, etc. I think this is what we have seen to some extent with TNF inhibitors and biologics. Will we see more of this with the third and fourth JAK inhibitor remains to be seen. So more drugs can change the market so that more people are being treated more aggressively and this is what drives managed care and insurance crazy because they think we just want to spend more money.

That's not necessarily true. But what is the big change that we're seeking? For me, the big change I'm seeking is long term success with any drug I use. Less progression, less surgery, less death. When I'm doing that, I know I'm winning the war.

We have to realize that RA is more than just drug management. RA is actually a biopsychosocial disease saying that it's not just a drug that's going to fix this problem or right the ship. RA management encompasses a lot of things that you must manage and manage expertly. Personal issues, lifestyle change, problems with family, problems with job, much, much more. Those are probably equally important as drug therapy.

Surgery when appropriately used can be way more important than drug therapy. This means that we are not always going to be the high priestess of or priests of, the science when it comes to managing RA and we may not always possess the magic bullets. Most of those are still locked up because we don't have one drug or two drugs that works in everybody. Means we need more help. We need you to do more, we need you to change, and no one drug is gonna fix this.

If you could identify one or two or a few measures that would give you an odds advantage, an increase in two, four or nine percent in the likelihood of response, would you not employ it to the benefit of your patient? We need to have that information. So what's going to make the big change in the future? Is it going to be the drug? Is it going to be the doctor?

Is it going be the disease itself? I believe that rooms and ingenuity will be the driving agents for change as we go forward. We need the right people at the right time. I can't tell you why, can't tell you how or when, can tell you that you need to be a part of the solution here. I'm going close with my patient Barbara.

She died in 2012 at the age of 67. Her diagnosis was rheumatoid arthritis. Arthritis. It was based on chronic symmetric polyarthritis involvement of the PIPs, MCPs, wrist, elbow, shoulders, knees, hips, and feet. She was strongly rheumatoid factor and CCP positive.

She had deformities, erosions, and contractures. Her list of medications is a long one. Prednisone, methotrexate, Enbrel, Remicade, Humira, sulfasalazine, Rituxan, hydroxychloroquine, Imuran, Kineret, cyclosporine, Orenzia, cyclophosphamide, intramuscular gold, non dapsone, IVIG, clinical trials, there's probably a few I didn't include. Her disease was complicated by uveitis, tendon ruptures, osteoporosis, numerous surgeries, Sjogren's syndrome, septic arthritis, numerous hospitalizations for serious infectious events, DVTs and much more. I'm telling you this because she once said to my partner, when I die, put on the autopsy report that rheumatoid arthritis killed me.

It was the cause of my death. You can help. The Warren RA needs all of our help. I'm Jack Cush, executive editor of roomnow.com. Tune into Room Now for more great information on the war on RA.

Thanks.