The decision : On Biologics or Not

[LiteBlueSkies]

If I go on Biologics that seems to be a lifetime decision.
If I go on Vedolizimab - what happens if you go off or substitute another biologic down the line ?
In general , for those familiar , how often do people here/elsewhere complain that their biologic choice was one they wish they hadn’t made .
I've read here and there - that Biologics "may not be" as effective as would be liked

The woman who did my colonoscopy Wrote ;
“A mild amount of inflammation in the last part of your small intestine called the term Ileum - seen also on the biopsies . Your colon(or large intestine) looked normal during the colonsocopy . However , the biopsies of the colon showed signs of active inflammation on a microscopic level. This is a non-specific finding”

How risky is it , for those with a lot of experience here ..would it be for someone , perhaps like me to
forestall Biologic , hoping that diet and exercise can control this process ?

I’m considering trying rapamycin for example. I don't know if it's a good idea, but i'm heavy now into eating Apples/oranges/Green leafy stuff and
higher fat , grass-fed hamburger and have no idea whether this helps or is a good idea. Also absolutely no sugar.

 

[Scipio]

How risky is it , for those with a lot of experience here ..would it be for someone , perhaps like me to
forestall Biologic , hoping that diet and exercise can control this process ?

I’m considering trying rapamycin for example. I don't know if it's a good idea, but i'm heavy now into eating Apples/oranges/Green leafy stuff and
higher fat , grass-fed hamburger and have no idea whether this helps or is a good idea. Also absolutely no sugar.

Crohn's is a serious disease. Not normally deadly but seriously debilitating and destructive to having a normal life. And serious diseases almost always require strong medicine.

Diet helps with Crohn's, but it is mild medicine. You need strong medicine to get this disease under control. As I posted on another thread:

The side effects of Crohn's biologic medications are real but very rare. The bad effects of uncontrolled Crohn's disease are real and very common. The biggest threat to the health of Crohn's patients is not the side effects of biologic drugs. The biggest threat to the health of Crohn's patients is uncontrolled or poorly-controlled Crohn's disease.

I tried for years to get by on clean living, exercise, and minimal Crohn's medication. My Crohn's was fairly mild, and so it didn't seem like I needed strong medicine. And the strong medicine's long list of potential side effects sounded so scary. And for several years I got away with it. But my disease suddenly got aggressive, and I soon found myself on an operating table with my chest cut open and the surgeon removing the inflamed lining around my heart, because my Crohn's had suddenly escalated into a major extra-intestinal manifestation by attacking my pericardium. Today I'm happily on much stronger medicine - Stelara injections. The Stelara has worked and my disease is well-controlled for over 6 years and counting - with no side effects. I just wish I had started it sooner.

So now I have a big scar down the middle of my chest to constantly remind me of my folly. My advice is don't increase your risk of a similar bad outcome by withholding the tools needed to control this serious disease.

 

[my little penguin]

Understand the “for life part “
You use the biologic until it stops working or causes side effects or insurance refuses to cover it anymore
My kiddo - we stressed over the for life part
He was 8 when he started remicade
That lasted 8 months till he had two allergic reactions (he is a very allergic person in general )
Humira at age 9
That lasted till age 14 then stopped working
He has been on Stelara since age 14
Now age 20
So while ideally it’s for life
Realistically there are more options for later if needed

 

[braveheart]

Don't be afraid of meds when you are dealing with this chronic disease. I agree with what Scipio explained, you are most likely to need strong med to control this.
And as soon as you get any side effect doctors will switch/adjust your treatment. If you get a remission you could eventually migrate to a softer treatment.
I hope this helps

 

[LiteBlueSkies]

Don't be afraid of meds when you are dealing with this chronic disease. I agree with what Scipio explained, you are most likely to need strong med to control this.
And as soon as you get any side effect doctors will switch/adjust your treatment. If you get a remission you could eventually migrate to a softer treatment.
I hope this helps

thanks

 

[Andersen007]

I was diagnosed with very similar findings as yourself 1.5 years ago. I am trying to manage it with strict diet (and by strict I mean.. currently I eat the same homemade enteral nutrition every single day, and nothing else), not because I do not believe in biologics, but because we all have a limited time how long it will take to exhaust all available therapeutic options, and I am trying to push it out as I am only in my late 20s. Also I am hoping that this way, there will be more medication options by the time I will need them. I wont lie, it is not easy, and the 2-3 times cravings got the better of me, I went straight back into a mild flare. I monitor calpro regularly and make sure it stays within reasonable levels (I try to keep it below 200, doesn't always work), but before diet I had it around 1500-2000. My quality of life in general is really good - just 2 weeks ago I made a climb of 2000 meters a single day, and reached a 4000m peak, and 90% of the time in the last months I have normal stool frequency, and mostly normal consistency, little to no pain - except of course partying and spending time with friends takes way more effort without alcohol and restaurants.

What I can say is the remission (defined by lack of any symptoms + okay-ish calpro) I have achieved a few times during the last 18 months has been very fragile. On the positive side I have learned a ton of my disease - what foods cause inflammation in me, what are usually safe, combinations, consistency, etc. - this way when I do decide to go for a serious medication hopefully combined with some of this knowledge remission will last longer. I am planning to do an MRE soon to see how things look inside vs when I was diagnosed, and adjust accordingly. I have a "lucky" trait -it seems like I can follow my level of inflammation live by checking my eyes in the mirror - whenever my inflammation is increasing, the blood vessels in my eye get way more visible, and vica versa.

I am particularly reluctant to take anti-tnf before having children. But, if I couldnt keep my calpro under control for many subsequent weeks, or the MRE would tell me things are significantly worsening, or I would just feel like I am fed up with such a disciplined life, I would probably go for it. I still want to try Pentasa though, its not in the standard of care anymore and considered ineffective for Crohn's compared to biologics, but after reading through all the studies, I strongly believe its worth a shot, especially if done next to my current approach.

I would definetly not recommend my approach, just wanted to share that in case you do decide to go down this road, its not all fun and games either. There is a lot of trial and error, disappointment, social anxiety and fighting involved, as well as regular monitoring as symptoms do not always correlate with the disease process.

 

[kiny]

I've read here and there - that Biologics "may not be" as effective as would be liked

A select few are effective. Many biologics are not efffective for crohn's disease.

-Etanercept, an anti-TNF, is not effective in crohn's disease.
-JAK inhibitors (while arguably a synthetic and not a biologic) are not effective.
-Entyvio (vedolizumab) is not effective for crohn's disease.

However, Infliximab, biosimilars and IL-23 blockers are able to induce remission, but are still only effective in around half of patients, with many also eventually losing response.

EN is very effective, with 80+% of patients going into remission, but compliance is low.

As far as diet, there is no evidence regular diets are able to induce remission. Popular diets like vegan/paleo/Mediterranean are certainly not able to induce remission.

There are studies trying to mimic EN with very specific diets, like CD-Treat, which shows promise, but there needs to be a lot more evidence before anyone can say these diets are effective.

A lot people who try to manage their disease with diets just have uncontrolled inflammation, and they will end up regretting the damage the inflammation caused. Uncontrolled inflammation can lead to fistula, stenosis, strictures and perforations. Crohn's diseasse is not a disease you can manage without being closely monitored.

Be careful when people claim they manage crohn's disease by just changing their daily habits, diets, doing workouts, or using herbs or probiotics. They either don't have crohn's disease, or are trying to sell you something.

 

[LiteBlueSkies]

I was diagnosed with very similar findings as yourself 1.5 years ago. I am trying to manage it with strict diet (and by strict I mean.. currently I eat the same homemade enteral nutrition every single day, and nothing else), not because I do not believe in biologics, but because we all have a limited time how long it will take to exhaust all available therapeutic options, and I am trying to push it out as I am only in my late 20s. Also I am hoping that this way, there will be more medication options by the time I will need them. I wont lie, it is not easy, and the 2-3 times cravings got the better of me, I went straight back into a mild flare. I monitor calpro regularly and make sure it stays within reasonable levels (I try to keep it below 200, doesn't always work), but before diet I had it around 1500-2000. My quality of life in general is really good - just 2 weeks ago I made a climb of 2000 meters a single day, and reached a 4000m peak, and 90% of the time in the last months I have normal stool frequency, and mostly normal consistency, little to no pain - except of course partying and spending time with friends takes way more effort without alcohol and restaurants.

What I can say is the remission (defined by lack of any symptoms + okay-ish calpro) I have achieved a few times during the last 18 months has been very fragile. On the positive side I have learned a ton of my disease - what foods cause inflammation in me, what are usually safe, combinations, consistency, etc. - this way when I do decide to go for a serious medication hopefully combined with some of this knowledge remission will last longer. I am planning to do an MRE soon to see how things look inside vs when I was diagnosed, and adjust accordingly. I have a "lucky" trait -it seems like I can follow my level of inflammation live by checking my eyes in the mirror - whenever my inflammation is increasing, the blood vessels in my eye get way more visible, and vica versa.

I am particularly reluctant to take anti-tnf before having children. But, if I couldnt keep my calpro under control for many subsequent weeks, or the MRE would tell me things are significantly worsening, or I would just feel like I am fed up with such a disciplined life, I would probably go for it. I still want to try Pentasa though, its not in the standard of care anymore and considered ineffective for Crohn's compared to biologics, but after reading through all the studies, I strongly believe its worth a shot, especially if done next to my current approach.

I would definetly not recommend my approach, just wanted to share that in case you do decide to go down this road, its not all fun and games either. There is a lot of trial and error, disappointment, social anxiety and fighting involved, as well as regular monitoring as symptoms do not always correlate with the disease process.

Thanks for your reply . My gastro guy doesn't ever give me any tests like calpro , my primary care doc will give me CRP . Eyes thing sounds interesting , but I have a great imagination. Will check it out though. I am very interested in your home concoction of EN . I have started in the last 2 weeks to drink a lot of stuff like "Ensure / Premier Protein / Gold standard Protein shake" and there is NO doubt it has made a difference in my stools and evacuation frequency. I evacuate anywhere from 24-70 hours now.

I think fibre is a killer for me though . I tried eating lots of fiber - salads/apples/green stuff and the result was catastrophic.

If you could , could you give me your EN home made receipe and I'll just leave out the fibre part . Thanks

 

[LiteBlueSkies]

A select few are effective. Many biologics are not efffective for crohn's disease.

-Etanercept, an anti-TNF, is not effective in crohn's disease.
-JAK inhibitors (while arguably a synthetic and not a biologic) are not effective.
-Entyvio (vedolizumab) is not effective for crohn's disease.

However, Infliximab, biosimilars and IL-23 blockers are able to induce remission, but are still only effective in around half of patients, with many also eventually losing response.

EN is very effective, with 80+% of patients going into remission, but compliance is low.

As far as diet, there is no evidence regular diets are able to induce remission. Popular diets like vegan/paleo/Mediterranean are certainly not able to induce remission.

There are studies trying to mimic EN with very specific diets, like CD-Treat, which shows promise, but there needs to be a lot more evidence before anyone can say these diets are effective.

A lot people who try to manage their disease with diets just have uncontrolled inflammation, and they will end up regretting the damage the inflammation caused. Uncontrolled inflammation can lead to fistula, stenosis, strictures and perforations. Crohn's diseasse is not a disease you can manage without being closely monitored.

Be careful when people claim they manage crohn's disease by just changing their daily habits, diets, doing workouts, or using herbs or probiotics. They either don't have crohn's disease, or are trying to sell you something.

Thanks for your post , you seem the most knowledgable . I'm gonna hold off on the vedolizimab. The transfusions would be free cause it's through the VA . Think I will hold off on that for now - as drinking lots of Ensure as an addition to my wheat/diary free [except for cheese , I love cheese] diet , is showing actual good results. Do you have ANY experience with Rapamycin/Sirolimus ? I'm interested in this .
It's supposed to be an Anti-Inflammatory - purposed for transplant rejection and used off-label for life extension type stuff .

 

[Guerrero]

A select few are effective. Many biologics are not efffective for crohn's disease.

-Etanercept, an anti-TNF, is not effective in crohn's disease.
-JAK inhibitors (while arguably a synthetic and not a biologic) are not effective.
-Entyvio (vedolizumab) is not effective for crohn's disease.

However, Infliximab, biosimilars and IL-23 blockers are able to induce remission, but are still only effective in around half of patients, with many also eventually losing response.

EN is very effective, with 80+% of patients going into remission, but compliance is low.

As far as diet, there is no evidence regular diets are able to induce remission. Popular diets like vegan/paleo/Mediterranean are certainly not able to induce remission.

There are studies trying to mimic EN with very specific diets, like CD-Treat, which shows promise, but there needs to be a lot more evidence before anyone can say these diets are effective.

A lot people who try to manage their disease with diets just have uncontrolled inflammation, and they will end up regretting the damage the inflammation caused. Uncontrolled inflammation can lead to fistula, stenosis, strictures and perforations. Crohn's diseasse is not a disease you can manage without being closely monitored.

Be careful when people claim they manage crohn's disease by just changing their daily habits, diets, doing workouts, or using herbs or probiotics. They either don't have crohn's disease, or are trying to sell you something.

I dont want to argue, but I think it’s wrong to say:
“Entyvio (vedolizumab) is not effective for crohn's disease.”
There are many studies proving Entyvio is effective for crohn’s disease (maybe percentage is not as high as infliximab, but that would still make wrong your conclusion), that’s why it’s aproved by many american and european drug agencies and insurance as a valid therapy. You can also read on this forum many success stories with entyvio.

 

[kiny]

I dont want to argue, but I think it’s wrong to say:
“Entyvio (vedolizumab) is not effective for crohn's disease.”

Vedolizumab is not effective.

One of the largest studies to date, 368 patients with crohn's disease. And this was a sponsored study where the maker could pick and choose the type of patients eligible for the study.

At 6 weeks, 6.8% of patients were in remission on placebo, only 14% in remission on Vedoluzimab.

That's an effective remission rate of 7%, which is even lower than mesalazine that doesn't have nearly the side effective Vedoluzimab has.

That 7% "remission rate" is already questionable, because they could not show a CDAI-100 response.

"At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission. Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response"

https://www.nejm.org/doi/10.1056/NEJMoa1215739?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0www.ncbi.nlm.nih.gov

Another study, at 7 weeks.

An effective remission rate of 8%. (41% placebo vs 49% vedoluzimab).

Again, lower than mesalazine.

"Clinical response rates at day 57 were. 49% in the MLN0002 0.5 mg/kg group
41% placebo group."

https://www.cghjournal.org/article/S1542-3565(08)00617-4/fulltext

 

[kiny]

Is Vedoluzimab effective at 52+ weeks? Who knows and who cares. Data at 52+ weeks without a placebo arm is completely unreliable.

Do people with crohn's disease with active inflammation have the time to wait 1 year before they achieve remission? No.

The fact is that Vedoluzimab has failed to achieve remission at 8 weeks in multiple studies and that makes it ineffective compared to EN, anti-TNF and IL-23 blockers that can achieve remission at 8 weeks.

 

[Andersen007]

I agree with Entyvio not being too effective esp for non-colonic disease (perhaps above numbers would have looked a bit better if they would have looked at Crohn's restricted to the colon?) unless patient can somehow afford to wait quite long.

But I wouldn't say the same about JAK inhibitors, obv it wouldn't be my first choice but I think the numbers aint that bad if all else failed
https://www.nejm.org/doi/full/10.1056/NEJMoa2212728e.g. at 12 weeks here endoscopic response of 35-46% vs placebo of 4-13%, with clinical remission of 40-50% vs 20-30% in placebo

 

[Guerrero]

Vedolizumab is not effective.

One of the largest studies to date, 368 patients with crohn's disease.

Only 14% of patients in remission at 6 weeks, compared to 6.8% on placebo.

That's lower than mesalazine that doesn't have nearly the side effective Vedoluzimab has.

"At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission. Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response"

https://www.nejm.org/doi/10.1056/NEJMoa1215739?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0www.ncbi.nlm.nih.gov

Another study, at 7 weeks.

An effective remission rate of 8%. (41% placebo vs 49% vedoluzimab).

Again, lower than mesalazine.

"Clinical response rates at day 57 were. 49% in the MLN0002 0.5 mg/kg group
41% placebo group."

https://www.cghjournal.org/article/S1542-3565(08)00617-4/fulltext

It makes no sense to watch data at 6 or 7 weeks, it’s well known for how it works that it takes around 10 to 14 weeks to be effective as it slowly change how new immunity cells work.

“After 1 year, nearly twice as many people had their Crohn’s under control after taking vedolizumab compared with people who had been taking placebo. About 39% (39 in every 100 people) who took vedolizumab had their Crohn’s under control compared with 22% (22 in every 100 people) who had been taking placebo.”
https://crohnsandcolitis.org.uk/inf...subcutaneous injection showed similar effects.

 

[kiny]

JAK inhibtors Filgotinib and Tofacitinib were both pulled from the market for crohn's disease because they were both ineffective.

And JAK inhibitors have very serious side effects.

 

[Guerrero]

Is Vedoluzimab effective at 52+ weeks? Who knows and who cares. Data at 52+ weeks without a placebo arm is completely unreliable.

Do people with crohn's disease with active inflammation have the time to wait 1 year before they achieve remission? No.

The fact is that Vedoluzimab has failed to achieve remission at 8 weeks in multiple studies and that makes it ineffective compared to EN, anti-TNF and IL-23 blockers that can achieve remission at 8 weeks.

Well, it’s a life long disease, and some patients may have had no response to any treatments unfortunately, so yes they can wait for 14 weeks or even 52 weeks.

 

[kiny]

It makes no sense to watch data at 6 or 7 weeks

After 1 year, ....

Inflammation doesn't wait 1 year. Fistula, strictures and perforations don't wait.

They don't wait 1 year (52 weeks) until Vedoluzimab "supposedly" works. I say supposedly because at 52 weeks you no longer have a reliable placebo control arm.

EN induces robust clinical remission at 4 weeks.
Anti-TNF and IL-23 blockers induce robust clinical remission at 8 weeks.

Vedoluzimab does not. I have a difficult time believing Vedoluzimab actually does anything, since it doesn't target a major phagocyte cytokine involved in crohn's disease.

Anyway, I have made my opinon on Vedoluzimab clear in the past, there is far more effective medication, have a nice day.

 

[Guerrero]

Inflammation doesn't wait 1 year. Fistula, strictures and perforations don't wait.

They don't wait 1 year (52 weeks) until Vedoluzimab "supposedly" works. I say supposedly because at 52 weeks you no longer have a reliable placebo control arm.

EN induces robust clinical remission at 4 weeks.
Anti-TNF and IL-23 blockers induce robust clinical remission at 8 weeks.

Vedoluzimab does not. I have a difficult time believing Vedoluzimab actually does anything, since it doesn't target a major phagocyte cytokine involved in crohn's disease.

Anyway, I have made my opinon on Vedoluzimab clear in the past, there is far more effective medication, have a nice day.

If it can’t wait then you use corticoids or EEN for a short period of time to induce remission and maintain it with biologics.

There are no certainty or valid studies so far concluding EEN is a valid solution to maintain remission and what are the long term effects of that kind of nutritions for years. Anyway I guess most of the patients are looking to maximize their chances for good heatlh and quality of life with a less stricter diet than EEN.

 

[NeverBeenEasier]

JAK inhibtors Filgotinib and Tofacitinib were both pulled from the market for crohn's disease because they were both ineffective.

And JAK inhibitors have very serious side effects.

Simply saying "X inhibitors have very serious side effects" is really a null point. All biologics, TNF-alpha, integrin inhibitors, Jak inhibitors all have potentially serious side effects. For the most part, all the serious side effects associated with biologics are extraordinarily small.

The FDA applied a Blackbox warning on all JAK inhibitors due to extrapolation of data surrounding the risks of venous thrombosis, MACEs, etc. SPECIFICALLY for Tofacitinib - which inhibits JAK 1 & 3 preferentially along with some JAK 2 inhibition.

Upadacitinib selectively inhibits JAK 1 so it is very much a different mechanism. Plus, for the most part, Upadacitinib actually works quite well for Crohn's disease, especially those with refractory disease.

I don't know what your background is, but unless you're a physician, going around speaking about the risk and benefits of specific pharmaceuticals is honestly unsafe and can push patients away from necessary medications. If someone is at the point where they need to start taking JAK inhibitors, it's pretty obvious their disease is quite refractory to a lot of the medications out there. It should be a serious consideration for them to start a medication that has quite a robust response so early on.

My last point, if your physician recommends hopping on biologics, there is a good chance your physician believes you'll be better off on meds than trying to control your disease through dietary and lifestyle management. Recent landmark study (PROFILE) has come out that has finally confirmed that a "top down" approach (starting with the big guns - biologics) should be the standard of care for those with moderate disease. Don't delay medical care out of fear of very low-risk side effects - not taking medication in and of itself is a major risk factor for disease progression and serious complications.