Comparative Effectiveness of Persistent Use of a Name-Brand Levothyroxine (Synthroid®) vs. Persistent Use of Generic Levothyroxine on TSH

[helvella]

We often see claims from the USA that Synthroid, "the brand name", is substantially better at treating hypothyroid patients than generic levothyroxine (GL).

This paper claims to demonstrate this is true. And that, despite the higher cost of Synthroid, its use results in lower overall medical costs.

But, even within the paper, it admits:

Our study examined GL utilization as a single cohort and did not differentiate between different generics, whose effectiveness may not be identical.

That implies some of the patients might have had different products, and different combinations of products, dispensed at each refill. We often discuss the non-interchangeability of levothyroxine products. It sets up the study to fall into Simpson's Paradox.

It ends up claiming, in effect, that no generic could ever be as good as Synthroid. Yet the paper fails to prove that at any level.

The paper is based on getting TSH into reference interval and costs of illnesses. No mention of well-being.

My view is that the paper exists ONLY to persuade those who foot the bills that despite the higher cost of Synthroid, they will save money overall.

I suspect you could have chosen almost any of the generic levothyroxine products as the reference product and achieved similar-seeming results. However, until properly researched, treat that as a guess based on cynicism.

Adv Ther. 2021 Dec 14.

doi: 10.1007/s12325-021-01969-3. Online ahead of print.

Comparative Effectiveness of Persistent Use of a Name-Brand Levothyroxine (Synthroid®) vs. Persistent Use of Generic Levothyroxine on TSH Goal Achievement: A Retrospective Study Among Patients with Hypothyroidism in a Managed Care Setting

Liya Wang 1 , Yaozhu J Chen 2 , Michael Grabner 3 , Bal Nepal 1 , Amit Bodhani 2 , Ramon Espaillat 2 , James V Hennessey 4

Affiliations

• 1 HealthCore, Inc, 123 Justison Street, Suite 200, Wilmington, DE, 19801, USA.

• 2 AbbVie, North Chicago, IL, USA.

• 3 HealthCore, Inc, 123 Justison Street, Suite 200, Wilmington, DE, 19801, USA. [e-mail].

• 4 Beth Israel Deaconness Medical Center, Boston, MA, USA.

• PMID: 34905150

• DOI: 10.1007/s12325-021-01969-3

Abstract

Introduction: Levothyroxine monotherapy (Synthroid® or multiple generic levothyroxine [GL] formulations) is standard treatment for hypothyroidism. Our objective was to compare effectiveness (as measured by achievement of thyroid-stimulating hormone [TSH] levels) and economic outcomes of Synthroid vs. any one of multiple GLs in patients with hypothyroidism.

Methods: Data for this retrospective cohort study were obtained from the HealthCore Integrated Research Database®. All study patients had ≥ 2 claims between 1 January 2006 and 31 December 2017 with ICD-9/10-CM diagnosis codes for hypothyroidism; were persistent users of Synthroid vs. any GL; and had ≥ 1 TSH laboratory result during 12-month follow-up. Patients were divided into one of two cohorts based on index medication and were 1:1 matched using propensity scores. The primary outcome was the proportion of patients with last TSH laboratory result during follow-up within the reference range (0.3-4.12 mIU/L). Secondary outcomes included all-cause and hypothyroidism-related healthcare resource utilization (HCRU) and costs.

Results: After propensity score matching, the Synthroid and GL cohorts each contained 18,382 patients. At follow-up, significantly more patients receiving Synthroid were in the TSH reference range vs. GL (78.5% vs. 77.2%, respectively, p = 0.002). HCRU and costs were broadly similar between the cohorts in terms of all-cause inpatient hospitalizations, emergency department visits, outpatient services, and pharmacy fills. Irrespective of index medication, patients with TSH within the reference range had significantly lower hypothyroidism-related medical and total costs compared to those outside the range.

Conclusions: This real-world data study showed Synthroid was associated with better TSH target achievement vs. GL in a US managed care population. Achieving TSH goals may provide substantial economic value by reducing hypothyroidism-related HCRU and costs.

Keywords: Comparative effectiveness; Hypothyroidism; Levothyroxine; TSH.

pubmed.ncbi.nlm.nih.gov/349...

Full paper freely accessible here:

link.springer.com/article/1...

If you are wondering why this paper is open access when so many are not, I suggest you read this statement from the paper:

Funding

Study funding was provided by AbbVie, Inc., to HealthCore, Inc. The study sponsor is also funding the journal’s Rapid Service and Open Access Fees.

link.springer.com/article/1...

[diogenes Remembering]

This paper is a nonsense. If different generics were used in different doses, no way could one compare Synthroid versus these unless they were separated into a comparison with each generic at the same dose. And that would take a very large study indeed to be meaningful. Getting TSH in range of course is another red herring that proves nothing, if at the same time patient reaction is not considered.

[BadHare]

Something that came up several times in my biomedicine lectures was that expensive branded drugs, such a painkillers, listed exactly the same ingredients as cheaper generic drugs so should work as effectively. As a painkiller user, I know this is definitely not the case!I've had a few conversations regarding this issue with a microbiologist friend who's worked in the pharmaceutical industry for over 30 years, often in a quality control or quality assurance role. Like a lot of things we're prescribed or buy, the basic ingredients including exponents & manufacturing process will affect how good any product is.

I've never taken synthetic T4 so cannot comment on this pharmaceutical, but I'd compare it to my experience with the different NDT brands. I've tried undrinkable £2.99 hangover wine & >£80 bottles. They've both been though the same manufacturing process but one should be poured down the sink, & the other heavenly. Some people regularly take the thyroid hormones that have disagreed with me as well as others being unable to tolerate my preferred meds & supplements.

[helvella Administrator Thyroid UK in reply to BadHare]

I agree that two different makes can have very different effects. But the more expensive is definitely not always the preferred one.

For example, some USA patients massively preferred Unithroid to Synthroid despite being less expensive (and, at the time, also supplied as a cheap "generic" by one company - leaving names out to try to avoid future confusion).

[jimh111]

Two things that drive me nuts in one paper.

1. So much for peer review. This paper is pure advertising and should not be published. As noted by you and diogenes there wasn't a one for one match with specific generics. Given Synthroid is expensive you would expect more careful monitoring to keep costs down.

2. We instinctively feel larger trials are better than small ones. However, if the effect is trivial it will only show up in a very large study. The example I give is that if you put a postage stamp in the heal of your shoes you will be taller. It would take a very large study to demonstrate this. This study states "the Synthroid and GL cohorts each contained 18,382 patients. At follow-up, significantly more patients receiving Synthroid were in the TSH reference range vs. GL (78.5% vs. 77.2%, respectively, p = 0.002). " 18,382 subjects and p=0.002 looks fantastic but an extra 1.3% within the reference interval is trivial, if it is indeed desirable.

[diogenes Remembering in reply to jimh111]

I also think that the editing power of the journal leaves a lot to be desired. Blatant attempts to increase usage of Synthroid should not appear in this or any other journal unless that journal is openly honest about its allowance of manufacturers to promote their products, And even then good science should prevail not this cherrypicking effort.

[Mlinde in reply to diogenes]

TUK shouldn't be promoting any particular brand of Levothyroxine (or NDT) given as how different they seem to work (or not) with different patients.

[helvella Administrator Thyroid UK in reply to Mlinde]

Do you consider the discussion, in strongly negative terms, of the subversion of the journal publishing industry and self-serving promotion by the manufacturer is promoting a particular brand of levothyroxine?

My view is that it simply informs that there are attempts by at least one manufacturer to promote their product using techniques I regard as deeply unethical.

Were Synthroid an option for me, I would be very much avoiding it on ethical grounds, and would only accept it if it there were no satisfactory alternative for me. That is, I wouldn't go to the extreme of (possibly) harming my own health to avoid it.

[Mlinde in reply to helvella]

Absolutely!

[helvella Administrator Thyroid UK in reply to Mlinde]

Could you please explain why you consider it promotion of a particular make of levothyroxine?

I'm afraid I cannot see in what way it promotes one make.

[Mlinde in reply to helvella]

Well, I think it's one thing to inform users of any potential problems with a drug/hormone but quite another to advocate that one product is superior to another, especially where thyroid treatment is concerned, after all, isn't that why TUK exists? Not that I'm saying TUK does this but I think this doc, 'Comparative Effectiveness' is misleading as it looks 'scientific' but in actuality it's a puff piece for a particular product.

One of the major topics here is just how variable Levothyroxine can be, if not the active ingredient then the fillers and what not. But the last thing we need to rely on is anything the manufacturer says about it. I think the piece that kicked this off treads a very fine line (I'm being generous).

Just to clarify, obviously, particular brands affect different people in different ways but that's not the same as saying a particular product is better than all the others, or advocating one product eg, Synthroid. Better for whom? I've read a lot here about sticking to one brand and that may well work for some or most but in my case, none of the Levothyroxine works regardless of the brand.

[helvella Administrator Thyroid UK in reply to Mlinde]

The whole point of posting was to point out that the paper is rubbish, not good enough to qualify as science, and grossly misleading.

You cannot call out a lie without identifying the lie you are calling out!

I used the same practice I always do of quoting the paper's title (or part, if too long) as the subject line for the post.

[shaws Administrator in reply to Mlinde]

I had to diagnose myself after GP phoned to tell me I had nothing wrong. I cried and had never heard of hypothyroidism at all ( if the word was stated it would have meant nothing to mel. None of the specialists I paid diagnosed me and I even went under an anaesthetic to 'remove 'web' !

My GP didn't realise (or know) what a TSH of 100 indicated as he phoned to inform me that my blood tests were fine and there was nothing wrong!

I cried.

It was thanks to Thyroiduk (before this forum began) that led me along the path to my proper diagnosis and also that there were other thyroid hormone replacements other than levothyroxine.

I can definitely state that, for me, levothyroxine only made me far more symptomatic and affected my heart beats too (in the middle of the night it was not rare to have palpitations of over 120+.p.m.

For me , only one thyroid hormone replacement restored my health.

If patients are still complaining the doctor should should permit options to be trialled

Before diagnosis, I even underwent anaesthetic to 'remove a 'web' from my throat. I had no such thing and when I was finally diagnosed correctly, did I realise that the 'web' was a swollen thyroid gland.

[Mlinde in reply to shaws]

Well 13 years ago I was diagnosed by accident. I had a blood test for an infection and by the way, I was informed that I had an underactive thyroid. I was never asked for any of the symptoms I had and I think it was 25mcg Levo to start with and within hours of taking it I got the most crippling pains in my legs when I walked more than a 100yds. 'Pure coincidence' I was told, nothing to do with the Levothyroxine. And then, about 3 years later, I woke up one morning and it was as if a veil had been lifted from my eyes! I realised I'd been in some kind of weird 'brain fog' for three years! I surmise that I had been underactive for much longer and somehow, my body had adjusted to life without a properly functioning thyroid (is this possible?). I think, looking back now that my thyroid had been wonky for at least 20 years!

The point is, the Levo never worked on me in 13 years, in fact I'm worse off physically now than I was before I started on it. Until very recently, I was on 100mcg and I reluctantly pushed it up to 125mcg because suddenly my symptoms got worse. Increasing to 125mcg, reduced my being cold, but only a little but all the symptoms I've had are still with me. I just don't convert enough T4. My vits etc are all pretty good. Elsewise my immune system is excellent! The last time I had the flu was 45 years ago and I never get colds and I've never been overweight, according to the doc, I'm underweight (I think she's wrong, I'm just a very lightweight person 5-10 and 135 lbs). I eat healthily and regularly, I just don't put on weight, don't ask me why.

[tattybogle]

confused ...........should i file this under "spam" or 'bollocks " ?

[helvella Administrator Thyroid UK in reply to tattybogle]

I did wonder if it broke guidelines on advertising on ThyroidUK/HU.

[Mlinde]

OK, point taken, but I don't think that was clear to readers at least judging by the responses to it. Wouldn't a summary have been a better choice perhaps and your reasons for posting it?

[Batty1]

I was on Synthyroid and it was pure poison they use Acacia in the 50mcg …. I will stick with my generic at least I don’t get jello legs, blistering hives and so much more.

[helvella Administrator Thyroid UK in reply to Batty1]

Keeping to the same make, once you've found one that works for you, is key.

[Batty1 in reply to helvella]

100% agree and Im so grateful you found that info for me or who knows what would have happened to me down the road …. That Acacia really needs to be removed from thyroid meds.

[helvella Administrator Thyroid UK in reply to Batty1]

I'd like to see it removed from absolutely all medicines. Seems little reason to use ingredients which are known to affect people, unless absolutely unavoidable.

(Obviously, for any ingredient, you might find someone, somewhere, who is intolerant. But at least to aim for zero intolerance seems entirely reasonable.)

[nightingale-56 in reply to helvella]

Acacia Powder was in Goldshield Eltroxin, but since then they have changed the way it is heat treated before it can be used. I wonder if this is the problem with Acacia Powder now.

[helvella Administrator Thyroid UK in reply to nightingale-56]

Could you explain about heat-treatment of acacia powder, please?

[nightingale-56 in reply to helvella]

A few years ago you posted a few pages of a, now out of print, Handbook of Medical Excipients. In it, it said under Acacia Powder, that it couldn't be used with soap unless it had been heat-treated. A couple of year ago on a facebook page someone had posted that heat treatment had been done a different way. When I first had problems with Mercury Pharma, it was after I had been taking it for about 3 months and my scalp felt very sore and I could taste soap in my mouth whenever I washed my hair. Then, when I had my hair coloured I could taste bleach in my mouth also. I felt it prudent to stop having my hair coloured then and can only infrequently use soap when I am washing my hair. I can't tell you how many bottles of 'once used' shampoo I have given away because I couldn't use them. Now, the same thing is happening while taking Erfa. WP was fine and it was so lovely not to taste soap in my mouth and having sticky spots appearing on my body. This is also happening to my son. Brings a whole new meaning to having my mouth washed out with soap from telling lies!

[helvella Administrator Thyroid UK in reply to nightingale-56]

Is this what you mean?

adiyugatama.files.wordpress...

[nightingale-56 in reply to helvella]

I think it was a much earlier version and was just a couple of pages at the top of the second page it stressed that it was not to be used with soap (hence the shampoo taste in my mouth?) unless it was properly heat treated. Sorry I can't be more explicit than this, and can't find where I have saved the piece.

[nightingale-56 in reply to Batty1]

I fully agree with you Batty1 . I am also finding Microcrystalline Cellulose a problem in Erfa (Armour is worse as this also had Acacia Powder in it), but this is all I can reasonably take now, until, hopefully, WP Thyroid comes back.

[Batty1 in reply to nightingale-56]

I was on Armour a long time ago and came off because I felt suddenly sick on it and actually thought cymbalta was causing a reaction but now you said it has acacia in it that explains a lot .

[nightingale-56 in reply to Batty1]

I could only take Armour for a few days before I realised it wasn't for me. I have to say, I have patches of nausea on Erfa.

[nightingale-56 in reply to helvella]

And then they take it off the market helvella , and have to start again.

[nightingale-56]

Thanks for posting that helvella . I still maintain that Goldshield Eltroxin was better than any Levo we have around today. My health and that of my son has certainly gone downhill since this was 'sold out' to Mercury Pharma.