A new test could save arthritis patients time, money and pain. But will it be used?
A new test could save arthritis patients time, money and pain. But will it be used?
Dr. Erinn Maury knew Remicade wasn't the right drug for Patti Schulte, a rheumatoid arthritis patient the physician saw at her Millersville, Maryland, practice. Schulte's swollen, painful joints hadn't responded to Enbrel or Humira, two drugs in the same class.
But the insurer insisted, so Schulte went on Remicade. It didn't work either.
What's more, Schulte suffered a severe allergic reaction to the infusion therapy, requiring a heavy dose of prednisone, a steroid with grave side effects if used at high doses for too long.
After 18 months, her insurer finally approved Maury's drug of choice, Orencia. By then, Schulte's vertebrae, weakened by prednisone, had started cracking. She was only 60.
Schulte's story of pain, drug-hopping, and insurance meddling is all too common among patients with rheumatoid arthritis, who often cycle agonizingly through half a dozen drugs in search of one that provides a measure of relief. It's also a story of how doctors are steered by pharmacy benefit managers — the middlemen of the drug market — as well as by insurers.
This reads like an advertisement for Orencia.
Biologics like Enbrel, Humira, and Remicade all act on slightly different parts of the TNFalpha pathway. Some patients respond to one and not the others. Also, biologics can become less effective over time, so many patients will switch from Enbrel to Humira after a few years.
Orencia is not a TNFalpha inhibitor, but a T-cell signaling inhibitor.
Think of your immune system like a demolition crew. If something is in your house that doesn't belong, they walk into the room, smash it to bits with hammers, and then someone else comes along and sweeps up the debris.
There are also people walking around your house looking for shit that doesn't belong, like spotters. They have the blueprints, and if they find something that shouldn't be there, they call the demolition team.
Rheumatoid and Psoriatic arthritis are the result of an overactive immune system. The people with the blueprints will walk into a dusty room and think "This wall isn't supposed to be dusty!" and call the demolition crew. The crew shows up and busts down the wall, kicking up more dust. The spotters see more dusty walls and call more demo teams. More people in the room, more demo, more dust, the cycle continues.
Incidentally, this is also more or less what causes allergic reactions and flu symptoms, except for those you have the Mucus Crew which comes in and hoses everything down with mucus. Fly got in the house? Smash it with hammers and then cover everything in mucus.
Anyways, TNFalpha is sort of like the hammers. Biologics like Enbrel, Humira, and Remicade all act on the hammers, making it harder to swing them or making them less effective at destruction. T Cells are sort of like the people with the blueprints. T Cells use two receptors to recognize foreign material, so think a measuring tape and a level. Orencia comes along and knocks the level out of the spotter's hand, so they are less likely to call the demo team.
Neither treats the underlying cause, the overactive immune system, and both treatments leave the patient more vulnerable to infections and leukemia. It also takes months to determine if they have been effective, because you have to heal the damage before you can determine that there hasn't been additional damage.
All that is a long way of saying, no doctor can predict which treatment will be effective. No doctor could predict that, if Enbrel and Humira have not been or stopped being effective, that Remicade wouldn't work. No doctor could predict that Orencia would work where the others had failed.
Neither can the insurance companies, of course.
This article makes it sound like the patient was forced to try something they knew would be ineffective before they were allowed to try a treatment they knew would be effective. There are four problems with that statement.
Medical decisions should be made by doctors and patients. Medical insurance companies shouldn't exist at all, at least not in their current form. So I agree that there's a problem here, but we don't get anywhere by misrepresenting what we know and don't know.
We know for a fact that around 50% of people with RA will not respond to TNF inhibitors and there's a blood test that can identify those people with about a 60% success rate, except insurance companies won't cover it?
That's not a non-story. That's clinically significant.
And the article mentions two other drugs in addition to Orencia, which are not t-cell signalling inhibitors. This is not an ad for a drug. It's a good article.
The patients were forced to take a drug that had a high likelihood of being ineffective without being permitted access to a test that has a high likelihood of detecting that ineffectiveness.
We don't know "for a fact" anything of the sort. We expect that only about 50% of people suffering from RA will have a >70% clinical improvement, while we would expect about 10% of patients who do not have an adequate response to TNF inhibitors to have a 70% improvement on abatacept. Source:
https://pubmed.ncbi.nlm.nih.gov/16162882/
Which is great. That's good news. >20% clinical improvement for most patients is the difference between being bedridden and being able to bathe and get around the house.
And yes there are some promising blood tests and genetic markers that would suggest the efficacy of biologics overall, see here:
https://www.liebertpub.com/doi/full/10.1089/nsm.2020.0007
https://www.medscape.com/viewarticle/835000
But neither the genetic test nor the interferon ratio tests are conclusive enough (yet) to be recommended prior to beginning treatment, nor do either even attempt to predict the efficacy of abatacept. It's a promising pathway for future research, but nobody is recommending routine blood tests to skip TNF inhibitor treatments yet.
I agree with you that we have a problem with medical insurance. For-profit payment providers should not be dictating treatments to doctors and patients, neither forcing certain treatments nor prohibiting clinically-proven effective treatments. That's major problem that needs fixing immediately.
We also have a problem with pop-science articles drawing sensational conclusions from limited data. Pharmaceutical companies promote their drugs like they're soft drinks. It would be much easier to argue that insurance companies have no rational basis for overruling decisions made by doctors and patients if we didn't have patients demanding the latest fad drug they heard about on a morning talk show.
I'm not saying this article is a paid advertisement, but if the drug company had written it, there wouldn't be much difference. I do think the author implies a more dramatic scenario than what exists in reality. Outrage is good for engagement, but just because the insurance company was wrong to intercede doesn't mean that the outcome was known in advance. Doctors have to live with uncertainty, and patients have a hard time accepting that their doctors are sometimes going with their intuition because the patient is the data needed to draw conclusions.
I look forward to better predictive tests and new treatments and therapies, since Humira seems to have stopped working for me and I might be moving on to Orencia next. I have the good insurance, so that's nice for me. But the world will be a better place if medical science directs treatments instead of profit and marketing, and journalistic integrity drives engagement instead of drama.