Upadacitinib clinical trial for UC

Is this your first JAK-Inhibitor biological? Out of curiosity, did you consider Xeljanz? You may have been able to get it off-label, it is also a JAK-inhibitor and you'd not had to of risked getting a placebo.

Xeljanz has been used for the last 5 years for RA. They will soon start using it for IBDs, it is currently being used by some UC'ers on HW.

/en.wikipedia.org/wiki/Tofacitinib

They are both orally administered.

Part of the reason I asked is because of the debate about if the 2nd biological you try is less effective than the first. So if you try Remicade first and then you move on to the 2nd Anti-tnf like Humira, it is less effective than Remicade. I was wondering if that worked the same for JAK-inhibitors as it does with Anti-tnfs biologicals.

The odds that you are refractory (non-responsive) to all UC medications increased as you fail a 1st, 2nd, and 3rd biologic.

How bad are your UC symptoms and your quality of life? Any plans for surgery should the Upadacitinib trial fail?

We've had many posters go through surgery for their UC, do well and wish they'd have done it sooner!

Barnsbury, how are things going?

After a ton of hoops and delays I just started a Upadacitinib trial 4 days ago here in the US. I’d guess it’s the same trial.

I’m 99% sure I’m on real drug. Not placebo. As I’m seeing changes starting on day 2 (crazy). So far it’s more formed stool (still small and broken up. But a lot better then near constant D). And less blood.

Having some discomfort I attribute to the more formed stool. Think my poor beat up colon isn’t quite ready for solid stuff.

Still a lot of trips and wakes ups in the night (I’ve been running about 10-15 trips a day, even with some Imodium to help me manage work during the day). But crossing my fingers that things keep improving. Hope you are seeing some relief.

Quick background: UC dx summer 2016. Constant flare since then. Humira started to help late 16’ but developed antibodies. Mesalamine drugs and even prednisone haven’t seemed to do much. Remicade helps some but my body washes it out in about 2 weeks. Insurance would only go for every 6 weeks. So taking a shot at a Christmas miracle with this study.

mapesg said...
Barnsbury, how are things going?

After a ton of hoops and delays I just started a Upadacitinib trial 4 days ago here in the US. I’d guess it’s the same trial.

I’m 99% sure I’m on real drug. Not placebo. As I’m seeing changes starting on day 2 (crazy). So far it’s more formed stool (still small and broken up. But a lot better then near constant D). And less blood.

Having some discomfort I attribute to the more formed stool. Think my poor beat up colon isn’t quite ready for solid stuff.

Still a lot of trips and wakes ups in the night (I’ve been running about 10-15 trips a day, even with some Imodium to help me manage work during the day). But crossing my fingers that things keep improving. Hope you are seeing some relief.

Quick background: UC dx summer 2016. Constant flare since then. Humira started to help late 16’ but developed antibodies. Mesalamine drugs and even prednisone haven’t seemed to do much. Remicade helps some but my body washes it out in about 2 weeks. Insurance would only go for every 6 weeks. So taking a shot at a Christmas miracle with this study.

Hi mapesg

Good to hear from someone else on this trial

I can't believe how quickly you responded to the drug. It took me at least 3 weeks to see any major improvement. It does sound like you are on the active drug. Well, I have now completed the intial 8 weeks of the trial and I had my 2nd trial colonoscopy last week. Although there was still quite bad inflammation in the left side of my colon, the rest of my colon had healed significantly. Which is great news.

So I was categorised as a "responder" to the treatment and moved into Substudy 3 and re-randomised. I have a 50/50 chance of real drug or placebo on this arm of the study. Its been a week tomorrow since I started on this and I havent felt any worse so I am really hoping that I stayed on the real drug.

My BMs per day are around 4 with no blood and rarely any mucus. Urgency is still there, but I have that even when in remission due to massive scarring from repeated UC flares over the last 17 years.

My abdominal pain has mostly gone too. And I no longer run to the toilet all night.

Are you on any steroids? How are you feeling now? Have you experienced any side effects? Please keep me updated on how you go.

Take care

Barnsbury,

How are you doing? Looks like I’m following a similar route as you. Deemed a responder, re-randomized. Crossing my fingers I’m getting the real drug (just started yesterday so too early to have a guess).

Scope at about 6 and a half weeks in found that my deep ulcers had cleared up. Still a total mess down there but they are saying they see a lot of signs of healing.

Down to about 4 BMs a day. I’d be content to stay at that rate. I still have blood here and there. And the quality of my stool varies quite a bit. I am being looser with my diet though and that seems to correlate wth some of my rougher bathroom trips. But even the bad trips seem a lot better then before the trial.

Hoping for more improvement. But if I had to stay where I’m at I’d take it. Very livable. That’s nice to say. And... hopefully I’m not on placebo. They can bump me to an open label study where I get real drug if I start to go downhill after something like 4 weeks. So I’ll be on the drug one way or another eventually.

Hope you are doing well.

iPoop said...
The odds that you are refractory (non-responsive) to all UC medications increased as you fail a 1st, 2nd, and 3rd biologic.

I’ve seen this stated a few times here. What is considered “failing a biologic”? Is it just people who never responded at all to the biologic? Or is it still considered failing the drug, if it eventually loses its effectiveness over time?

If anyone knows the answer to this, I’d love to know, thanks!

mapesg said...
Barnsbury,

How are you doing? Looks like I’m following a similar route as you. Deemed a responder, re-randomized. Crossing my fingers I’m getting the real drug (just started yesterday so too early to have a guess).

Scope at about 6 and a half weeks in found that my deep ulcers had cleared up. Still a total mess down there but they are saying they see a lot of signs of healing.

Down to about 4 BMs a day. I’d be content to stay at that rate. I still have blood here and there. And the quality of my stool varies quite a bit. I am being looser with my diet though and that seems to correlate wth some of my rougher bathroom trips. But even the bad trips seem a lot better then before the trial.

Hoping for more improvement. But if I had to stay where I’m at I’d take it. Very livable. That’s nice to say. And... hopefully I’m not on placebo. They can bump me to an open label study where I get real drug if I start to go downhill after something like 4 weeks. So I’ll be on the drug one way or another eventually.

Hope you are doing well.

Hello mapesg

Good to hear from you and glad to hear that you are doing well.

Well a fair bit has happened since last time. After I got re-randomised, my symptoms started to slowly worsen. After around a week or so, the number of BMs went up and I was having to run into shops to use the toilet when I was out and about which wasnt the case before.

Also, the (mild) side effects that I was getting before stopped. (Strange dreams). Then the abdominal pains came back, etc. So, I was sure I was moved onto placebo. So, after 6 weeks I was moved onto the open label. You need to have 2 "unscheduled loss of response" appointments 2 weeks apart to be eligible for open label.

I have been on open label 15mg for 10 days now, and things are improving again. Some days I only have 2 BMs with no blood, which is amazing. Though today i had 4. So, its up and down but its definately improving. Also the strange dreams came back! Have you experienced any side effects?

It is deeply disappointing that my healing was interrupted with the placebo and I moved backwards just when I was doing so well. But, that cant be helped. I hope you manage to avoid placebo.

There are 3 of us on open label at my hospital now. Also, I think your steroid taper is a bit too fast, I could never come down that fast. But, then I have been on steroids for most of the past 18 years and now my adrenals are shot. I would drop by 1mg a month after 10mg and then at 5mg I switch to hydrocortisone which has much shorter half life than pred and makes taper easier. Its what worked for me last time.

Best wishes, keep us posted on your progress.

No reason to be scared. There's new biologics every year or two. Some have been on remicade for 8-10, or more years without issue. Same will go with newer ones like entyvio. in the end, only 20-ish percent of us ever need a surgery, while 80% of us do not need it.

Thanks for sharing details. This medicine sounds hopeful. I just took my last loading dose of Entyvio today. I can't say I have seen any improvement from it yet.