Early immunotherapy for Crohn’s disease significantly reduces complications
newatlas.com
newatlas.com
> anti-TNF drugs, such as adalimumab, work similarly to infliximab and are significantly cheaper, more research is needed to establish whether they’re clinically effective
Adalimumab has been extensively tested and has been prescribed in the UK for at least 9 years - as that's how long I've been on it. The NHS wouldn't be prescribing it if it wasn't clinically effective.
Both medications are monoclonal antibodies for TNF-alpha, but are slightly different in formulation. Infliximab is a chimeric monoclonal antibody derived from a mouse/human cell lineage, whereas Adalimumab is derived solely from human sources.
My understanding (from the consultants at the research hospital where I am a Crohn's patient) is that Adalimumab is a) more expensive than Infliximab and b) less likely to trigger the patient to develop an immune response after a long prescription period, as the chimeric cell lineage can be recognised by the immune system as "foreign" after a while. I'm not a clinician so I can't really speak to the correctness of this statement, but anecdotally that's what I have been told by my consultant.
I am not sure that Infliximab is more expensive either. From what I understood at the time of my prescription, Adalimumab (Humira) was the more expensive drug, although prices have dropped significantly since then.
We got a generic Adalimumab formulation on the market in the UK about 3-4 years ago - until then, we were using AbbVie's Humira which I believe cost the NHS about £400/pen at the time. As I understand it, Infliximab is cheaper than this - although the generic Adalimumabs are also cheaper (~£80/pen IIRC).
They both have roughly the same target, but Adalimumab is a more recent, technologically superior in every way, design. I'm frankly not 100% sure why any doctor would want to start someone on Infliximab in 2024 if Adalimumab was also available. I think the kind of doctor who does this is the kind of doctor who hasn't caught wind of the fact that early treatment with the best biologics leads to better patient outcomes (this is not the first paper that suggests this, it's a trend in clinical research that dates back at least 15 years). More traditionally, Infliximab was given first, and patients who failed that treatment were then "ramped up" to the equivalent but superior Adalimumab.
Nowadays the state of the art is to start with Adalimumab right off the bat, or even better, one of the newer biologics: either an integrin targeting one like Natalizumab or Vedolizumab (I admit to not being as up to date on this therapeutic avenue as I am on the others), or an IL23/IL12 targeting one like Ustekinumab (although the latter has already been obsoleted by the more p19-selective Risankizumab).
My gastro says he simply sees better results on infliximab than he does on adalimumab across all his patients, so he tends to start people on the former first. I think the fact that it's an infusion versus a shot does make a difference. AFAIK very few of his patients end up failing infliximab and switching to adalimumab, other than the ones who don't respond to TNFis period.
(Worth noting here that I actually was on twice-monthly adalimumab prior to getting a Crohn's DX, so I'm definitely one of those people for whom infliximab is a better choice. The adalimumab helped with spondylitis pain to an extent, but GI imaging at the time still came back definitively Crohn-y!)
My doctor put me on low-dose MTX for this exact reason—here's hoping I never start to develop infliximab antibodies...
Regarding the price, I would also have to assume they're comparing generic v generic (even though generic adalimumab wasn't available in the US until this year!), so I wonder if the reason they're saying infliximab is more expensive is because of the associated nursing labor/infusion clinic/IV supply costs. I only paid five bucks for my meds at the last infusion, but had to pay $160 for them to infuse it in me!
Also, side note, the fact that a name-brand Humira pen "only" cost the NHS £400 in the UK (and likely cost even less for patients) is blowing my mind. They retail for about $3500 a pop here :(
All that said, it's not a massive cheap free-for-all on medication - in the UK we've still got hospital/NHS trust budgets which have been iteratively slashed by a decade of successively worse Conservative governments, so generally the inclination is for the NHS to prescribe the (much) cheaper generics.
That said, our healthcare providers get very creative with pricing, so I don't know how Adalimumab compares. It's never been suggested to me.
This study is not really net-new information, but it does add to the pile of evidence in favour of the more aggressive treatment approach. There are still a very large number of specialists who have not yet updated their views.
On that side note- Pondering a mive to the US from the EU, how does one go about moving a medication regiment like this to avoid disrupting the schedule?
Depending on/asking for help from an employer (if they are helping you move) is a good first step though.
Edward Huang with PAMF is the guy I go to, if you’re moving to the bay area.
Bring as many doses of your current meds as you can with you. How quickly you can get in to see some one will depend on where you are in the US. Ask them to put you on a cancellations call list if your appointment is further out, they will sometimes call if they have a cancellation and you can get in earlier... depends on the practice. Emphasize with them when you talk to scheduling how urgent it is because you need to continue your meds. Be kind in all your interactions, and they can often find ways to work you in if they understand how urgent it is.
Don't be afraid to call around to find a specialist with an earlier opening, even if you change specialists later becuase one is a better fit.
Worst case I could fly home to get it (6 months until free care ends after moving away fromwhere I am now), and I could bring 3 months with me.
This makes planning for an eventual move way easier.
For a move from US to EU without employment insurance (which may grant you coverage for existing issues), you will need to go through your state marketplace which is more expensive but should have plans that covers it (by law).
Original text:
I just did such a move from the USA to France. After seeing a specialist in the country, I got access to something called “ALD” (“affectation de longue durée” aka long term chronic issue). This grants me 100% coverage for anything related to my crohn’s, including surgeries and the drugs mentioned in this thread. Note that the drug itself is also capped at $500 per box of 2 pens due to French regulation on drug prices, vs $5000 without insurance in the U.S.).
Disclaimer: I’m French American.
I was hesitant at first thanks to how many MTX horror stories I've heard, but those dose is so small that I thankfully haven't experienced any side effects. Just 7.5mg once a week.
A recent Dutch single-blind RCT (van der Kraaij et al. 2023 [1]) on adalilumab on psoriasis with/without methotrexate reported very favorable results after one year. However, when they their third-year update basically concluded that the effect was not real. As a counterpoint, many of their patients exited the study by the end of the third year (sometimes due to adverse events), and so at the end they had just 8 patients left in total. They use some statistical techniques to account for this, but I'm not a statistician and don't know if they make sense. Some commentary here [2].
As an aside, it's interesting that most studies typically look at ADA (anti-drug antibody) serum levels and not actually at clinical efficacy. A few studies do look at both.
I'm inclined to think that it's better to be safe than sorry, but that's in spite of the evidence.
Regarding MTX horror stories, there are some things one can do to prevent/alleviate side effects [3]. One thing that's not known by most doctors is that a lot of people (maybe as many as 40% of the U.S. population) have a genetic mutation that impacts the body's ability to activate folate. The MTHFR 667CT genotype reduces folate activity by about 35-40%, while having two copies of the mutation (677TT) reduces it by about 70-80%. Since MTX is a folate antagonist and folic acid is taken to counteract this, it means that for many people, the folic acid doesn't do its job. There are two alternatives (folinic acid and L-methylfolate), both widely available by prescription, that don't have this problem, and some rheumatologists swear by them. A formulation called Rheumate (L-methylfolate plus curcumin) was developed specifically for use with methotrexate.
[1] https://pubmed.ncbi.nlm.nih.gov/37014287/
[2] https://onlinelibrary.wiley.com/doi/10.1111/jdv.19282
[3] https://rheumnow.com/content/dsb-managing-methotrexate-toxic...
And yeah, I'm also inclined to think "better safe than sorry" here, especially with how cheap generic MTX is :P
Re. the folic activity: this does seem like it could explain a lotttt of negative experiences I've heard! It doesn't seem like I'm one of the 40%, but my dose just might be too low to tell. If I ever need to up my dose, I'll definitely ask my rheumatologist about Rheumate :)
In my case, my dermatologist put me on Taltz straight away, skipping all of my insurance company's preferred first drugs because the complication rate was much lower. Even if my insurance company would have covered it, the co-pay would have been impossible to keep up with.
However, with their other org covering the cost, I think I ended up paying something like $25 a dose for what was at the time several thousand dollars retail price.
All of that is to say, if the health insurance plan your company has doesn't want to cover it, it might be worth reaching out to the manufacturer to see if they will help. At the very least, they may be able to recommend a US based specialist to get you a new prescription if the specialist pharmacies here don't respect a foreign prescription.
Edit: here's the specific program I went through: https://www.taltz.com/savings-support
If you scroll to the "Declaration of interests", you will see that the authors are heavily entangled with the drug industry. That doesn't mean the study is wrong, but ...
HN community, why can't we regularize, if not automate, the very simple process of linking to studies rather than thin rewrites of studies? When a study assesses a commercial endeavor, why can't we regularize tagging it with the author's interest in that endeavor?
[1] https://www.frontiersin.org/journals/immunology/articles/10....