Thursday, 14 Nov 2019

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War on RA - Part 3: Useless Drugs

In 1998 Dr. Jim Fries surveyed US rheumatologists on the advances or milestones in rheumatology in general and, specifically RA.

In 1998 – the major advances were early aggressive therapy and combination therapy.

IN 2008, I repeated the survey and found that TNF inhibitors, early aggressive therapy and methotrexate were the milestone advances.   

Not or low on the list were CCP, the shared epitope or a greater understanding of RA. When asked what was most disappointing about RA; you said the cost of care, managed care, lack of timely referral, lack of a cure and lack of an etiology.

What would a survey of today’s rheumatologist yield?  I dare say – Drugs, drugs, drugs.

We have options that are endless – we have 28 biologics in rheumatology; 19 approved for RA in the last 20 years, but 15 of these are me-too copies or biosimilars.  We currently have 2 JAK inhibitors and may have 3 or 4 by year end. 

The facts are that your next best prescription written for RA will fail in 30-50%; half will not be on that drug in 2 years and the 15-35% of patients who stop your Rx for toxicity will forever be jaded about taking your next best suggestions for disease modification. 

What we really need is the right drug at the right time – but how can we know. .

Many of you think drugs are the answer. But they are just the new kid in town - How well does that play out? 

Are you guessing with each prescription you write?  Why is it that all clinical trials with our best new drugs essentially have “noninferior” efficacy compared to the other standards or other new competition?  

Currently the major differences between drugs are:

  • Pill vs shot (pt. acceptance of your recommendation)
  • Marketing and name recognition
  • Your familiarity (which is why we tend to rely on the same ole agents)
  • Which one is preferred or forces on you or the patient by managed care?

Managed care?  You mean the industry to whom we entrust our patients welfare, the one that is driven by Billions in income and millions in bonuses to make the choice of preferred or tiered therapies?  You mean the industry that has GED knuckleheads wasting my staff time with prior authorizations to maximize their profits while redirecting care according to the algorithm on the screen – wait more like a Crayola list of 2-3 drugs.  The industry that forces me, when I go to bat for my patient - to talk to a dyslexic physiatrist who cannot spell canakinumab and has no clue what RA is?

Your management of RA – MOSTLY SUCCESSFUL – is rooted in knowledge, experience and the utmost interest in patient well fare.  However, your therapeutic choices are at best educated guesses and at worse, therapeutic adventurism. Only to be confounded by the idiocy and greed of insurance and managed care and only to be complicated by patients uncertainty over a new medication.

If I am correct that it’s a toss-up as to whether Orencia is a better choice over Enbrel, then managed care is justified in their forcing choices based on financial incentives that benefit everyone but the patient or physician.  Instead of being money driven should the choices be based on new data or big data?

Today we published a report from the Swedish registry showing real world performance when choosing the first or 2nd biologic in RA – better efficacy was seen with RTX and TCZ, non-TNFi biologics compared to the TNFi.  The differences here were as much as 10-25% with the non-TNFi biologic.

Similarly there are data suggesting, if you prefer to use certain Biologics (namely ABA, RTX) in seropositive RA you may do 10% better.

Life's been Good for many of our patients, BUT I believe that the great advances in RA are yet to come and that the next milestone with be from better science, smarter management (driven by data) and not necessarily new drugs.

Where can new drugs make a difference?  And they can...

I believe the greatest new difference with new drugs is when there are enough of them that the paradigm changes.  This is an example of tipping point sociology and seen when you look at the introductions of statin drugs, the first being lovastatin (Mevacor). The use and impact of statins didn’t change or skyrocket until the 4th or 5th one was introduced (Lipitor).  The equation for change was time, product succession, pivotal trials showing bigtime benefits beyond primary endpoints (surgery, death, hospitalization etc.).  Then statins changed the way CV disease was managed, mainly because they changed the most important outcomes.

We’ve seen some of this with TNFi and biologics. We may see more of such change with the introduction of a 3rd or 4th JAK inhibitor.  

But the big change we seek is what?  For me – long term success, less progression, less surgery, less death – that’s where we need to be to win the war.

RA is a biopsychosocial disease; meaning is takes more than “a drug” to fix this problem or to right the ship.  RA management encompasses personal issues, lifestyle changes, family concerns, work challenges and more.  Means you may not be the high priestess of Science and your magic bullets are still unknown to you.

This means we need more help than any one drugs can offer us.

We need you to identify the other 2 or 3 or 6 measures needed to increase the odds of success by 2-4-9 percent per patient per prescription.

So what will make the biggest difference in the future – the Drug, the disease or the doctor?  Clearly we need change - I believe that rheums and ingenuity will be the driving agents of change.  The right people at the right time.  I Can't Tell You Why, how or when. I can tell you that you need to be a part of the solution.

My patient Barbara died in 2012 at the age of 67 yrs. Her diagnosis is based on chronic, symmetric polyarthritis, involvement of PIPs, MCPs, wrist, elbow, shoulder, knee, hip, and feet, with a high titer RF and CCP, deformity, erosions, and contractures.  Her prior therapies included prednisone, methotrexate, Enbrel, Remicade, Humira, sulfasalazine, Rituxan,  imuran, Kineret, cyclosporine, Orencia, cyclophosphamide, Plaquenil, intramuscular gold, NSAIDs, Dapsone, IVIG, and numerous clinical trials. Her disease was further complicated by uveitis, tendon ruptures, osteoporosis, numerous surgeries, Sjogren’s syndrome, Septic arthritis, numerous SIE, hospitalizations, DVT and more. 

She said to my partner – “when I die, put on the autopsy report, that RA killed me.”

This is the third of a four part series devoted to the War on RA – We need to change the standards, rethink the approach, be innovative and look for help to win the war on rheumatoid arthritis. Your comments, suggestions, and ideas are needed!

Read War on RA - Part 1: Walk on the Moon

Read War on RA - Part 2: It's All About You

 

 

 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Rheumatologists' Comments

Tremendous post, erudite and cogent. Much appreciated

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