It's interesting that the article states that Infliximab is more expensive than Adalimumab.
> 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).
> trigger the patient to develop an immune response after a long prescription period
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 :(
It costs nothing in the UK as it's covered under the National Health Service. Well - I say "nothing". All British citizens pay "national insurance", but it's effectively a regressive tax that's not based on the individual's health (as insurance would be), so some folks are effectively subsidising others. To give you an idea of cost, my NI contributions are about ~5.5% of my salary, but that also goes towards the state pension.
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.
The pricing on Humira in the US feels like a scam, although I'm not totally clear on who--the insurance companies? My insurance covers some % of the astronomical price, I put the rest on a credit card, and AbbVie deposits that money right back into my bank account, minus $5. After about two or three iterations of this, my out-of-pocket maximum has been reached for the year, and I've paid $10-15, minus credit card cash back. I guess having Crohn's has an upside.
I've been getting a biosimilar to Infliximab for several years to treat Crohns. I go in for an infusion every 8 weeks; about 6 times per year. I can only tell you the cost on the invoice from US providers, but it's about $10k for each infusion. $60k per year.
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.
I’ve been on infliximab for a while. My insurance (in USA) pays about $1800 for the drug + the 2 hours of time in the infusion center. It’s even cheaper (for the insurance company) to do an at home infusion.
I think maybe what the article is saying is that they didn't test giving Adalimumab early, so they don't know if that is as clinically effective as the Infliximab that they did test early.
I can tell you that Adalimumab is going to be at least as effective as Infliximab, and probably marginally better, at a minimum. This will obviously vary by patients, but Adalimumb is simply a superior design (it has comparable-to-somewhat-superior epitope conformation/selectivity, and has a humanized Fc part which has a much more favourable immunologic profile), and tends to statistically outperform.
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).
> I'm frankly not 100% sure why any doctor would want to start someone on Infliximab in 2024 if Adalimumab was also available.
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!)
The top down approach has actually been the state of the art in America for the last 5-10 years. It has been the state of the art in Europe since at least 5 years earlier than that-- And the conflict between the two schools of thought has been very interesting to observe.
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.
I was about to come comment that I got put on monoclonal antibodies basically immediately when I got diagnosed 4 years ago. I opted for Stellara bc it's mechanism overlaps with potential Celiac treatment.
I got this last year, after being on oral meds for a while. One downside I was told is the risk of rejection/allergy to the medicine if treatments aren't given regularly.
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?
I have never made such a move, but here is what I would do at a minimum, having dealt with healthcare in the US a lot. I would make sure I qualify for health insurance through work immediatly on starting. If not, you may have to pay for a few months on a healtcare exchange plan, which will likely be expensive but provide bridge coverage. Get signed up immediately. Know whether or not you will need a refferal to visit a specialist. Bring copies of your medical records with you. If you can go straight to a specialist, find a GI doc, maybe one that other chrons patients in your new area recomend, if you can find anyone online or know anyone in your area. Otherwise, get setup with a primary care doc and see if they will prescribe the meds based on your medical records or reffer you out... it will depend on the doctor and their comfort with the meds and your issues if they will be willing to do this, so expect to be reffered to a GI specialist. Emphasize how urgent it is. Even if you go straight to a specialist, get setup with a primary care doc right away, too. Don't be afraid to change doctors or seek a second opinion.
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.
I don't know how common this is, but for some Very Expensive Medications, drug manufacturers such as Lilly will run non-profit orgs that will help you get them dirt cheap if your insurance won't cover them.
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.
I’m originally from the UK, but it might still apply - it’s much more normal in the US to go straight to a specialist without a referral from a GP. If the company you’re moving with isn’t helpful you will probably be able to arrange directly with a GI doctor’s office with little effort.
Edward Huang with PAMF is the guy I go to, if you’re moving to the bay area.
EDIT: not sure if the post was edited or I misread you… I was reading US -> EU
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.).
Find a local doctor as soon as possible. The precise details will very much depend which country you go to in the EU. If you are moving with the help of a company, I would help their HR can help you with such details.
Regarding the rejection, ask about low-dose methotrexate! It helps prevent your body from building up a resistance against those sweet, sweet monoclonal antibodies.
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.
The evidence here is actually very slim. There are some studies that show a mildly positive effect on drug survival, but of these, the longest studies have typically been only a year or less.
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.
Oh, interesting; thanks for the links! One thing you might find notable is that my gastro wasn't the one who put me on MTX, even though he's the one who put me on infliximab—a rheumatologist suggested it. Although that rheumatologist didn't have me on MTX when I'd previously been taking adalimumab under his care. Not sure why he suggested it for one TNFi and not the other!
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 :)
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?
The incident count for very early onset Crohns is rapidly increasing [1]-- I wonder if they'll start to make these drugs available for younger children since today it's more or less forbidden for them to be used on kids under 16.
Have there been studies showing the long term effects of anti-TNF drugs? I'm specifically worried about the tumors that might escape being nipped in the bud if tumor necrosis factor is limited. I've always been concerned about this..
> 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).