Researchers announce findings from landmark clinical trial for pediatric Crohn's disease

[J100]

Hi All - Some latest research done by University of North Carolina.

https://medicalxpress.com/news/2023-04-landmark-clinical-trial-pediatric-crohn.html

 

[asadmom]

I don't get it. What did they find? Humira + mtx better than Humira alone?

 

[Scipio]

I don't get it. What did they find? Humira + mtx better than Humira alone?

Yeah, they found that, but they also found that Remicade + MTX was not better than Remicade alone. Which is at least mildly surprising to me. I would have expected those two biologics to behave the same in that respect.

 

[asadmom]

I thought MTX is always prescribed along with Remicade to lower the chance of the body developing antibody to the drug?

 

[J100]

@Scipio - Don't the two biologics work in the same way?

 

[Scipio]

I thought MTX is always prescribed along with Remicade to lower the chance of the body developing antibody to the drug?

It often is, but monotherapy with Remicade or Humira is not unheard of.


"@Scipio - Don't the two biologics work in the same way?"

In theory, yes. They target the same protein, but that doesn't mean they behave identically in all respects. It's common right here on this forum to find patients for whom Remicade works great but Humira not so much. And vice versa.

 

[kiny]

Remicade is almost always given as monotherapy nowadays to reduce risks. Combo therapy has become very rare.

What they instead do with some patients is dose escalation, so they decrease the time between infusions.

Some people break down these molecules faster than others, through protease. You can measure this. Remicade half-life is just over a week.

What also changed completely is how they give remicade to people. It used to be given once and was stopped. Now it is given every 8 weeks to patients. Another thing that changed is that they now start Remicade with a 2 week, 4 week, 8 week lead-in. It limits the chance of developing antibodies.

They also are more careful about latent TB with patients now. Some hospitals didn't used to do a mantoux test, so you had TB reactivation in some people with latent TB. Now they properly screen people before giving people remicade.

They also didn't used to let people drive their car when infliximab was first tried. Because it is a biologic, a new type of medicaiton, and they had no clue when an anaphylaxis reaction could take place. So people who were given infliximab in a hospital could not drive home. Now they know what the reaction looks like, they know when it happens, so people can just drive home.

Remicade has always been slightly more effective than other anti-TNF. Its mechanics are slightly different and it is also weight based, which makes it more appropriately dosed.

I found how other anti-TNF are dosed always weird, you're giving a young adult with half the weight the same dosis as an adult. It is because people want to take it at home so they make one size fits all injections, but this means improper dosing for patients. It means increased risk for people with low weight, and sometimes ineffective dosing for people with higher weight. Remicade is more correctly dosed.

 

[asadmom]

Remicade is almost always given as monotherapy nowadays to reduce risks. Combo therapy has become very rare.

What they instead do with some patients is dose escalation, so they decrease the time between infusions.

Some people break down these molecules faster than others, through protease. You can measure this. Remicade half-life is just over a week.

What also changed completely is how they give remicade to people. It used to be given once and was stopped. Now it is given every 8 weeks to patients. Another thing that changed is that they now start Remicade with a 2 week, 4 week, 8 week lead-in. It limits the chance of developing antibodies.

They also are more careful about latent TB with patients now. Some hospitals didn't used to do a mantoux test, so you had TB reactivation in some people with latent TB. Now they properly screen people before giving people remicade.

They also didn't used to let people drive their car when infliximab was first tried. Because it is a biologic, a new type of medicaiton, and they had no clue when an anaphylaxis reaction could take place. So people who were given infliximab in a hospital could not drive home. Now they know what the reaction looks like, they know when it happens, so people can just drive home.

Remicade has always been slightly more effective than other anti-TNF. Its mechanics are slightly different and it is also weight based, which makes it more appropriately dosed.

I found how other anti-TNF are dosed always weird, you're giving a young adult with half the weight the same dosis as an adult. It is because people want to take it at home so they make one size fits all injections, but this means improper dosing for patients. It means increased risk for people with low weight, and sometimes ineffective dosing for people with higher weight. Remicade is more correctly dosed.

Wow... had no idea. Is there any surprise or unknown stories about Stelara?

 

[kiny]

Idk if it's an unknown story, but the reason Stelara exists is because patents on Remicade expired and biosimilars came onto the market.

Stelara has slightly worse remissions rates than Remicade. The main cytokine macrophages secrete is TNF and IL1, no one expected that blocking IL23 would improve things. It still brings down inflammation, but is slightly less effective and it takes longer since the the medication acts on the IL23 pathway.

 

[asadmom]

Idk if it's an unknown story, but the reason Stelara exists is because patents on Remicade expired and biosimilars came onto the market.

Stelara has slightly worse remissions rates than Remicade. The main cytokine macrophages secrete is TNF and IL1, no one expected that blocking IL23 would improve things. It still brings down inflammation, but is slightly less effective and it takes longer since the the medication acts on the IL23 pathway.

I hear most people commenting on the slow acting of Stelara as the major drawback. Why does blocking IL23 take time? Is it also the same reason why it has a safer profile compared to antiTNF?

 

[kiny]

TNF promotes inflammation through leukocyte migration. IL23 acts on Th17 cells.

If you block TNF you interfere with the ability of the body to recruit more blood leukocytes, it is a more direct inflammatory pathway.

 

[kiny]

Not sure if Stelara is any safer than Remicade, it would be much more difficult to attribute side effects to IL23, but that doesn't mean it is safer though.

If someone develops TB reactivation 2 weeks after their first remicade infusion, it's easy to attribute that to a TNF blockade.

But if someone develops a staph infection after 6 months of Stelara, because you have been blocking IL23, they might not attribute that to Stelara in studies, since it's hard to prove the IL23 blockade caused it.

 

[kiny]

The main thing that is hard to control is reactivation. You can protect your kid or yourself from acute infections by just limiting unnecessary contacts with sick people, cooking meat well to avoid foodborne infections, avoid contact with certain animals that cause zoonotic infections.

The problem is latent infections. TB, herpes zoster, there is nothing you can do about that except getting enough vitamin D, zinc, etc. Avoiding unnecessary psychological stress that we now know impacts the immune system. That's pretty much all you can do, the rest is hard to control.

 

[my little penguin]

@kiny
You mention IL-1 to treat crohns
Anakinra (IL-1) and Canakinumab (IL-1) are used in anti inflammatory disorders
Limited case studies for pediatric crohns (one or two that I know of )
Neither did anything for crohns side of things for my child

 

[my little penguin]

Six years of Stelara here with no issues on infections

 

[my little penguin]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531243/

 

[kiny]

Not to treat crohn, it's just one of the main cytokine intestinal macrophages secrete, it activates T cells.

 

[kiny]

I said a few years ago that we won't make any progress with anti-inflammatories.

There's about 40 known interleukins, the most relevant being IL23 for crohn's. There's a small TNF family where anti-TNF works well to block inflammation.

JAK inhibitors failed for crohn's disease, and their safety is questionable.

Remicade / Stelara is the ceiling for treating crohn's disease with anti-inflammatories. Biosimilar brought the cost down, but we will need to look at other types of treatments to improve outcomes now.

 

[Scipio]

The main thing that is hard to control is reactivation. You can protect your kid or yourself from acute infections by just limiting unnecessary contacts with sick people, cooking meat well to avoid foodborne infections, avoid contact with certain animals that cause zoonotic infections.

The problem is latent infections. TB, herpes zoster, there is nothing you can do about that except getting enough vitamin D, zinc, etc. Avoiding unnecessary psychological stress that we now know impacts the immune system. That's pretty much all you can do, the rest is hard to control.

For Herpes zoster there are also vaccines to reduce the risk of reactivation: Zostavax and the newer and more-effective Shingrix. I've had them both over the years.

 

[Soryan]

What they instead do with some patients is dose escalation, so they decrease the time between infusions.

Some people break down these molecules faster than others, through protease. You can measure this. Remicade half-life is just over a week.

How to differentiate whether I am just metabolising fast or the drug is actually failing?

My trough drug level is higher than range but with undetectable antibodies. GI said the biologic is not working well on me.