[bdcravens]

I have CF, and I take Trikafta. Before Trikafta, I usually had a 5+ day stay in the hospital every year, and sometimes I have would very stubborn respiratory infections that just wouldn't go away. I was mentally preparing myself for inevitable decline and eventual death.

Trikafta changed my situation dramatically. I've had no hospitalizations, and most the classic CF symptoms are either gone or extremely diminished. It can't undo a life of damage to things like my pancreas, vas deferens, etc, and I still take medicine to digest my food, but overall, it's as close to "normal" as I could hope for at this point.

The only real downside: weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame, and went up some 6 inches in the waist. To add insult to injury, it happened during the spring and summer of 2020, when buying clothes was a challenge due to the pandemic.

Speaking of the pandemic, the timing of Trikafta was amazing: it kept the normally full "CF floors" of hospitals empty, opening up those beds for those with COVID and keeping CF patients less exposed.

One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.

(copied from the last time Trikafta was mentioned here: https://news.ycombinator.com/item?id=37540731)

[therein]

One of the first friends I made in college was a friend with CF. I didn't know what CF was. He was very mature for our age and generally a very nice, happy, caring person. Got internships, studied with us. Went to bars with us but never drank because he couldn't. He had stories about how Make-a-Wish foundation has been dragging their feet not to give him his wish since his childhood.

He would take his enzymes, do the vibrating jacket treatment. He graduated and got a full time offer from a nice company. As he was relocating, he picked up some infection and passed away in a few weeks. None of us expected it. This was months before I heard of the approval of Trikafta.

[bdcravens]

Never had a problem drinking. (So much so that I had to quit a few years ago)

[therein]

It was more of an I don't want to risk it kind of thing. He did taste it a few times towards the last few years of college.

[joney_baloney]

My younger brother has CF and takes Trikafta and it's absolutely made all the difference in the world, it's wonderful to see. Watching all the years of research and CFF funding finally pay off is really something.

My personal situation is probably pretty unique, in that I have CF as well, but had a double lung tx many years ago. A couple years ago my transplant team (actually it may have been the CF people.. fuzzy memory) asked me if I was interested in getting on Trikafta and after thinking it over for about 30 seconds I told them I'd probably pass. It seemed like it wouldn't have any beneficial effect on my lungs, as they no longer "have CF", and that I assumed it would just make extra weight for my decently healthy but still under par lungs to have to drag around. They didn't disagree.

[Sammi]

Yes but CF affects all liquids in your whole body. You can get diffuse long term damage anywhere and everywhere in your body. Having to eat calorie amounts like someone without CF sounds like a good tradeoff in order to not risk this damage.

[joney_baloney]

Yeah and it'd help my sinuses too but at my age I'm used to taking the enzymes when I eat and they work well enough. Long term damage is basically my personality at this point, lol.

[abdulhaq]

I'm in a similar situation so it's funny to see someone else here with the same. I had my transplant in 1988. There's also Steve Rasmussen (you can google him) who AFAIK also does not take Trikafta.

[COGlory]

Sorry for the potentially insensitive question, but I really am wondering about this:

>One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.

I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?

[junon]

Just an anecdote.

My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us).

He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke.

He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.

[bdcravens]

Most of us, especially adults, are pretty much settled in with the state of our condition - we've had it our entire lives. Anecdotal, but many CF patients (including in online communities I'm a part of) have reported a lot of increased anxiety.

[mason55]

> I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?

There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal.

So it seems to be a bit of an open question and I'm sure an emotional one on both sides.

[ipaddr]

Clinicians are always a day late and a dollar short. The evidence comes from these people reporting. These clinicians need a 50 million dollar grant to get that proof.

[TechnicalVault]

If you've ever had to organise a scientific study you'll understand why. Privacy and ethics are important but they make recruitment of a large and representative sample for any medical study a nightmare. First you'll need to run your protocol past an ethics board and do back and forth until it's agreed. Once you have that done you'll send out an invite (often blind) in hopes of getting people who fit your study aims and you will get who you get. There are often costs associated with this.

So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses.

Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion.

tldr; medical and scientific studies are hard if you want them to actually have any validity.

[AdamN]

It seems like we really need to move forward to 'indefinite/active studies'. I believe some researchers are trying to get onto this pattern but of course there are major privacy/quality of care concerns.

By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).

[markus92]

These kind of platform trials are getting more common luckily! Famous example is the COVID Recovery trial.

[pas]

wouldn't this side-effect become visible in Phase4 data? (and there should be at least some hints of this in the previous ones)

so, what I'm trying to say is that for this particular drug we "just need to wait", no?

[matthewtse]

(I left a previous comment as a similar sufferer of a lifelong genetic disease that was cured by a breakthrough medicine: https://news.ycombinator.com/item?id=37541222)

Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before.

A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.

[therein]

Just an anecdotal experience so doesn't necessarily mean anything but the only person I knew that had CF had absolutely no anxiety from his condition.

If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.

[vkou]

People generally get acclimated to the situation they are in.

If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.

[fnordpiglet]

I grew up with a lot of money insecurity, was homeless for a while and started my career with nothing - one change of clothes and a floor to sleep on. I’ve since done very well for myself and have a considerable amount of net worth at this point and a lucrative forward for as long as I want to keep working at it.

I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had.

That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.

[TotalCrackpot]

That's interesting - does your career require any formal education? Or were you able to develop some crucial skill on your own? Can you share what is your career about and where you started and where are you now? For example - do you hire employees or are you a landlord now, or are you an employee?

[fnordpiglet]

No, I’m a software engineer. I barely graduated high school because I was too busy smoking pot and programming at a time when you needed a degree to get a good job so didn’t have much opportunities despite being pretty skilled at programming. I got a job at Netscape tho as one of the first tech companies that didn’t look at credentials before skill. I did well there and did my own companies. But before I had nothing and move to California with $5 and a change of clothes, slept on the floor of someone I randomly met on irc (I was lucky it didn’t turn out worse than it did don’t try this at home!) until I found a job. Anyway, after Netscape and my startups I became a quant on Wall Street, finished my cs degree, and have had a successful career since. Now I’m the top IC at a late stage startup.

[TotalCrackpot]

I don't really see how you become a quant on Wall Street before you finish the CS degree, they I think look at credentials a lot, can you at least give the name of the prop shop that hired you without a formal education? Did you have any good results in algorithmic competitions or math competitions in high school? And how did you learn programming without an actual computer? Did your parents buy you a computer when you were young?

[pfannkuchen]

You might even have more with 15M! It’s much harder to replace if you lose it.

[cbeach]

On the subject of correlation/causation, I once took a drug called Accutane to cure my teenage acne. Listed side effects included: "Mental health issues depression, psychosis, aggressive behaviour and suicide ideation and attempts"

Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects.

However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem.

For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge.

So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.

[dan-robertson]

Yeah a lot of the side effects you listed sound a bit like they could be within normal expectations for teenagers, or just slightly heightened. Reminds me of an SSRI that happened to also massively reduce caffeine metabolisation without anyone noticing, and loads of the known side effects were really just effects of caffeine overdose – insomnia, jitters, headaches, etc.

[ipaddr]

It takes a lot including many suicides to get that side effect listed. You are lucky it didn't reach that point for you. With a little more time or repeated usage it probably would have got you as well.

[paulpauper]

weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame

This seems like a no-brainer way to treat obesity, by restricting or blocking such enzymes. Obviously the downside is diarrhea and other malabsorption symptoms, but obese people have too much nutrition. Blocking absorption seems easier than dieting, as no willpower required. You shit out the undigested food.

[derefr]

They sort of tried this in the '90s — not in the form of suppressing the required enzymes for nutrient absorption, but rather in the form of diet foods that contained inherently non-absorbable nutrients. The downsides were basically the same — the non-absorbed nutrients had to come out. People didn't generally respond well to these products. See e.g. https://web.archive.org/web/20060113084223/http://www.zug.co...

[vrc]

Olestra! I ate a whole bag of the Lay’s with Olean as a kid. They had the audacity to say that they assumed that people would only eat a handful at a time. Of near zero calorie potato chips that taste like potato chips…

[vrc]

Orlistat. Look at Alli — very available to buy. A very common side effect is steatorrhea. Oily leakage/poops. But not like, “oops I gotta run to the bathroom” but like, a tiny bear down and oil shoots out your bum. There is a clear warning on it about malabsorption as well of fat soluble vitamins.

[Scoundreller]

Having taken orlistat in low/intermittent doses, I can say it really matters what you eat fatty stuff with, on top of quantity. A regular "balanced" low-mid fat diet, and you're (well, I've been) okay.

If you eat a tub of ice cream as dinner, you're going to have a bad time.

[patmorgan23]

Appetite suppression/regulation seems like a much better route to pursue than intentionally inducing malabsorption.

[bdcravens]

I've played with my enzyme dosage, and there are a lot of unpleasant side effects as you've mentioned. Overall, the best approach has been what everyone else has to do: watch carbs and sugar, reasonable exercise, etc.

[7thaccount]

I had a close family friend (many decades older than me) lose his young daughter to CF back in the 60s or 70s. He and his family helped run the CF walk each year in their area and I'm sure made some major donations to research regarding it.

Hearing about any kind of advancement is huge. I can't even begin to understand what you've gone through, but am so happy to hear there is a new medicine to help with such a cruel disease and that it's made a world of difference to you. Sometimes it feels like medical science is still in the dark ages and I get saddened that we haven't got flying cars or Dr. Beverly Crusher can't wave some device over me and fix all the ailments I now have. Other days I hear about these kinds of advancements and it makes me smile!

[jMyles]

Reading your comment, I was certain I remembered it - and I see that you've now added a link to its previous home.

So I just wanted to say: it was an impactful piece of writing, enough so that I remembered it quite clearly after a single read these few months ago.

[bdcravens]

Thank you. My aim isn't to wax poetic or elicit sympathy, but to provide insight for others.

[cogman10]

> The only real downside: weight gain.

Interesting. I'm an uncle to a family member with CF (and I'm a carrier) and one of their long battles has actually been weight. To the point of doing things like downing olive oil to try and keep up the weight. They've eventually had to take the fairly drastic measure of getting a feeding tube installed. Getting enough calories in just hasn't been possible until the feeding tube.

[bdcravens]

Yeah, it's been quite a shock trying to reverse the first 40+ years of my life where I was told to eat eat eat. Not just for the weight, which is really a vanity thing, but also to counteract the diabetes that most with CF develop, since that can directly impact overall health and the ability to fight off infection.

[pedalpete]

Can you elaborate on the weight gain? I'm curious why that is a downside of the Trikafta? You say with CF the pancreas is blocked, so why did the weight come as a side-effect of the drug, and not with the disease initially?

[abhisuri97]

Med student here. My guess is the following: So with CF your pancreas can’t secrete many of the enzymes that are necessary to actually digest food. You can take medications to help with that digestion, but regardless, you aren’t actually getting all the calories in your food with CF because it isn’t making its way into your body (notably patients with CF have steatorrhea which is fat in their stool because they can’t absorb a lot of fat from their foods like a non-CF patient). The med helps the pancreas recover some of its ability to secrete digestive enzymes and so patients can now eat and get more from their food. The issue is that there needs to be a recalibration in terms of how much patients are eating. Previously a 2000 calorie diet may not have gotten them so far because they didn’t absorb much of it, but now they’re absorbing a lot more of it. Plus increased work of breathing with CF expends more calories compared to a non-CF patient (and patients on this drug).

[joney_baloney]

This is exactly right.

Source: have CF.

[bdcravens]

Some of the blockage of the pancreas is due to scarring, some of it to thick mucus. The scarring can't be undone, but with a reduction of mucus blockage, food may be digested better. That said, I think that there's other causes, given how fast most who start Trikafta gain weight.

[sunnybeetroot]

Assuming your anxiety medication is an SSRI or similar, your weight gain could be attributed to this as it’s been observed in people who take these medications.