u/5u114

Up until the last month, I lived a *somewhat* active lifestyle. I went on long brisk walks most days, with my dog, mostly in the woods. I ride motorcycles. For 'home gym' type exercise, I use an air bike, a rowing machine, I do strength training with free weights.

I can't do any of this right now. I've already put on a good chunk of weight in the last 6 weeks of this. Obviously I can eat less, but that's not the point ... I worry that the mortality rate associated with certain autoimmune conditions can be placed squarely at the feet of simply being unable to do any kind of meaningful cardio exercise, thus leaving your cardiovascular health in a poor spot.

Background: I had auto immune conditions start up, coincidentally enough when COVID started, beginning with skin issues, then bowel issues. I am on a multiple years long waiting list to see a dermatologist because the skin issues aren't severe enough I guess, but in the mean time my GP eventually settled on a psoriasis diagnosis (after first thinking seb derm - maybe it's both).

Then bowel issues started, and that also took a couple years to be finally seen to - and I was diagnosed with Crohn's. Tried some non-biologics interventions first, which helped symptoms a lot - including skin - but didn't produce the level of healing required for my small intestines. So, eventually, and recently, I started biologic therapy.

Specifically Entyvio, which is gut selective. The GI team were initially suggesting Humira, since it had a wider scope and could address skin issues (and upper back pain & stiffness - which I had been experiencing for a while - assuming that was autoimmune related). I suggested trying Entyvio first since the skin issues etc may resolve if they are extra-intestinal manifestations of the Crohn's disease, rather than independently co-ocurring autoimmune conditions. They agreed that made sense.

After the first infusion, didn't feel great, but nothing serious. I just took it easy, and backed off any exercise or physically demanding activities - just took it easy. Decided to take it easy until I was in the maintenance stage. I didn't think much of it at the time, but I did notice one of my knees occasionally give a little ache here and there when I would climb some stairs.

After the second infusion, within 48 hours or so, the same knee developed full blown enthesitis and swelling.

Turns out, this has been observed in new Entyvio patients. It is in rheumatology & gastro journals. It has been observed enough that there are meta-analyses on the papers published about it. Some papers strongly indicate / suspect a causal relationship, some are inconclusive, and the meta-analysis was ultimately inconclusive too. So basically they see it happening, but can't say with certainty why it's happening. But this is to be expected, to some degree, with observational studies.

At any rate, it's happening, it's being observed, and it's happening enough that they are actively publishing papers about it (which all generally come to the same conclusion that it should be researched further).

So, as far as I'm concerned, the timing of this is too much of a coincidence for it not to be directly or indirectly caused by Entyvio.

So I see the GI team about it, they're skeptical, say they haven't seen this before. They refer me to a rheumatologist. Takes a couple weeks to be seen. By then, on that very day, my knee was in the best condition it has been in for this entire 6 weeks - typical poor timing. But, in saying that, it was still obviously swollen, still had fluid on the knee, and still was stiff and limited mobility - just nowhere near as severe as it was a couple days previously.

Rheumatologist also didn't like the idea it was caused by Entyvio, cited the same meta analysis I read (I happen to have a science degree, for what it's worth, so reading medical literature was 90% of my work for my degree) - but I made it clear I didn't share her interpretation of the meta-analysis findings (she falsely represented it as the meta-analysis proved there was no link. It was inconclusive, not the same thing - but I digress).

Anyways, she aspirated the knee to analyse the fluid to rule out infection & gout. On the spot, she felt like this was an autoimmune arthritis - could be PsA, SpA, just generic IBD / autoimmune arthritis - she wasn't willing to pinpoint a specific form of autoimmune arthritis, since the treatment would be the same - biologics. She offered a steroid injection that day, but I declined because I seriously thought that whatever was causing this had passed, since my knee had improved so much that day. She told me I could come back for a steroid injection if I changed my mind.

I really regret not taking that shot, because within 24 hours my foot was sore, and within 48 hours my knee enthesitis was back to full blown swelling, pain, stiffness, severely limited mobility.

At any rate, whether it is a paradoxical side effect of the Entyvio, or an awfully suspiciously timed coincidence of a genuine progression of my IBD / Psoriasis / Autoimmunity into the development of arthritis .... the net result is changing biologics.

So now I am waiting for the Entyvio to flush out of my system entirely before starting a Stelara biosimilar.

Anyways, I'm in agony, pain is severe while sleeping, I'm sleeping in like blocks of an hour or so before pain wakes me up ...it could be a month until the rheumatologist can see me to inject steroids into the knee. And 3 months until I start the new biologic.

Ultimately I'm depressed at the idea that this may be my new reality ... not being able to do meaningful cardio exercise is really troubling me. Up until now, I was coping with autoimmunity by living an otherwise very healthy life - no bad habits, diet & exercise on point. In my mind, I could at least mitigate the severity of the autoimmunity by eating well and exercising. But if my knees, or ankles, or feet, or anywhere from the spine down to the toes are fucked up with arthritis / enthesitis - that's going to put an end to the type of exercise that keeps your cardiovascular system healthy.

Shit, I can barely get from my bed to the toilet. My poor dog isn't even getting a short, slow stroll most days.

Anyways, thanks for listening to my TED talk - I suppose I'm fishing for people to tell me they got their PsA / enthesitis under control and are exercising normally, and are fit. If anyone is living that life, please let me know. I need to know such people are living that experience.

For example, if I had an A0 sized screen & design, but could only use an A4 sized printer to create the positives - this would mean the design could be printed across 16 A4 film/transparency sheets to make up the full A0 design (16 A4's = A0).

But could these 16 A4 tiles be cleanly exposed to create a seamless, singular A0 screen ?

16 A4's to A0 is probably an extreme example. In reality, what I would actually like to do is more like stitching a couple A1's to make an A0 ... Or maybe 4 A1's to make a 2A0.

Extra time and effort isn't really the issue, it's more a case of is this possible to do in a seamless fashion, repeatable every time without relying on luck ?

Also, assume that the design can't be separated out into individual components - assume the whole design is connected from one corner to it's opposite, occupying the whole A0 space.

Most obvious challenge that occurs to me is cutting the borders off the individual sheets.

Let's say you manage to do that just right ... it's probably still likely that somehow the edges where the sheets are sitting beside each other messes with the exposure in one way or another, so the lines are visible somehow ?

Just wondering what people's experiences are on the biosimilars for Stelara / Ustekinumab ... specifically Wezlana or Pyzchiva.

I often see people have a bad time moving from the original biologic to the biosimilar. Sometimes I wonder if it's the switching over itself, rather then the biosimilar specifically, which causes the poor performance.

Like I wonder if you started on the biosimilar would you have a better experience than starting on the original and then switching. I wonder this because I have also seen some people report that they were fine on the original, moved to a biosimilar and had a bad time - but stuck it out and after several months ended up back in the same good place they were at with the original.

Anyway, I digress, I'm just curious who is using these biosimilars and what your experience has been - as I am likely to start on Wezlana or Pyzchiva in a couple months or so. I am not currently on Stelara. I started my first biologic, Entyvio, recently. Two infusions but had a bad reaction to it so I will be switching biologic.

Just wondering what people's experiences are on the biosimilars for Stelara / Ustekinumab ... specifically Wezlana or Pyzchiva.

I often see people have a bad time moving from the original biologic to the biosimilar. Sometimes I wonder if it's the switching over itself, rather then the biosimilar specifically, which causes the poor performance.

Like I wonder if you started on the biosimilar would you have a better experience than starting on the original and then switching. I wonder this because I have also seen some people report that they were fine on the original, moved to a biosimilar and had a bad time - but stuck it out and after several months ended up back in the same good place they were at with the original.

Anyway, I digress, I'm just curious who is using these biosimilars and what your experience has been - as I am likely to start on Wezlana or Pyzchiva in a couple months or so. I am not currently on Stelara. I started my first biologic, Entyvio, recently. Two infusions but had a bad reaction to it so I will be switching biologic.

The main argument I have heard against Valve subsidising the Steam Machine, and I think (if memory isn't playing tricks on me) Valve staff may have even made this argument directly around the launch announcement media appearances, is that because the Steam Machine is essentially a PC - they can't subsidise it because someone could buy it (or many of them) and never actually buy any Steam games. They could use it as a PC, or simply use it to play games bought elsewhere, or previously owned games. Etc.

OK.

However, it's not like Valve don't have an obvious way of getting around this.

All Valve would have to do, to counter this specific concern, is to subsidise the Steam Machine through an up-front expense on the consumer end which is leveraged/'refunded'/'rebated' against future discounts on Steam game purchases, which Valve would then use their revenue share to finance.

For example, let's say they *have to* sell the Steam Machine for $1,000 (just to pick a simple figure) ... but what would really be more palatable to their target consumer base is $800 (another simple figure, and also my personal limit for the 2tb SKU) - All Valve would have to do is offer $200 worth of Steam discounts, by simply discounting part or all of their revenue share (30% in most cases) per Steam game purchase. Until $200 has been 'refunded'/'rebated' to the consumer.

It wouldn't even matter if this stacked on sale prices, since it's going to amount to the same revenue expense on their end either way - but they could insist that the discount/'refund'/'rebate' would only apply to full price purchases - which would be a boost to the developer's selling games on their platform. But I digress.

Yes, this means Valve are subsidising the console. But it completely addresses the argument against subsidising which is based on the idea that someone could just buy the subsidised hardware and not buy any games. Anyone doing that would be paying full price for the hardware, and Valve wouldn't be subsidising them.

The idea could be tweaked here and there to make it even more certain that the people being subsidised are genuinely Steam gamers, or that Valve are still making money through the process of issuing the 'refund'/'rebate' (partial revenue share rather than the whole 30%)

So if Valve don't want to subsidise the Steam Machine, fair enough - but don't tell me it's because they can't be sure the buyer isn't just going to use it as a PC and not buy any games.

What am I missing here ?

No previous history of arthritis, inflammatory or psoriatic.

Waiting for rheumatology to investigate before proceeding with further Entyvio doses.

May not turn out to be psoriatic arthritis, but the symptoms are the same. Could be reactive arthritis, isolated enthesitis ... but for all intents & purposes, the symptoms are the same as psoriatic arthritis. In my knee.

Fuck this. I hate that I was worried about biologics, specifically adverse reactions and side effects, and it turns out I was right to be worried.