After nine years of routine bloods, my liver has finally given up tolerating 6-Mercaptopurine.
I have a GP appointment in two weeks, and gawd knows how long before I see my NHS consultant.
So that I can bone up prior to seeing the GP, what are my options?
As a fellow chronic illness person (Three Different Ones) – I have a controversial way of getting help. I use our robot friend, ChatGPT. I feed it all of my test results, symptoms, and anything else useful. It can sometimes give better advice than the doctor can. There’s always a risk with this sort of thing, and you need to educate yourself a bit before you blindly believe what it says.
Anyway, this time I just fed it your question. Answer in reply…
When a person with Crohn’s disease or IBD can no longer tolerate 6-Mercaptopurine (6-MP) due to liver toxicity, they will need an alternative treatment. There are several options depending on their specific case, including disease severity, past treatments, and any other underlying conditions.
1. Alternative Immunosuppressants
Since 6-MP is an immunosuppressant in the thiopurine class, switching to another drug in a different category might be necessary.
• Azathioprine (Imuran)
• A similar drug to 6-MP but sometimes better tolerated. However, since 6-MP is a metabolite of azathioprine, there’s a good chance that the same liver toxicity could occur.
• Blood tests can assess how the body metabolizes thiopurines (such as TPMT or NUDT15 enzyme testing) to determine if switching is viable.
• Methotrexate
• A widely used alternative for Crohn’s disease, often given as a weekly injection or oral tablet.
• Requires monitoring for liver toxicity and folic acid supplementation to reduce side effects.
• Mycophenolate mofetil (CellCept)
• Occasionally used off-label for IBD when thiopurines or methotrexate aren’t tolerated.
2. Biologic Therapies (More Commonly Used Today)
If 6-MP was part of a combination therapy or not working effectively, biologic therapies might be a better option. These target specific immune pathways instead of broadly suppressing the immune system.
Anti-TNF Biologics
• Infliximab (Remicade) – IV infusion every few weeks
• Adalimumab (Humira) – Self-injected every 1–2 weeks
• Golimumab (Simponi) – Used mainly for ulcerative colitis but occasionally for Crohn’s
• Certolizumab pegol (Cimzia) – Similar to Humira, used in Crohn’s
Anti-Integrin Therapy
• Vedolizumab (Entyvio) – IV infusion every 4–8 weeks, gut-specific with fewer systemic effects
Anti-IL-12/IL-23 Therapy
• Ustekinumab (Stelara) – IV induction, then injections every 8–12 weeks, good for both Crohn’s and psoriasis
3. JAK Inhibitors (Small Molecule Drugs)
• Tofacitinib (Xeljanz) – Approved for ulcerative colitis but being studied for Crohn’s
• Upadacitinib (Rinvoq) – Recently approved for Crohn’s
• These are oral medications, but they have more systemic immune effects than biologics.
4. Lifestyle & Adjunctive Therapies
While not a replacement for medication, these might help manage symptoms while waiting for a new treatment:
• Low Residue Diet / Elemental Diet (doctor-supervised)
• Probiotics (VSL#3, etc.) – Mixed evidence, but some find them useful
• Low FODMAP / Anti-inflammatory diets
• Curcumin (Turmeric) Supplements – Some evidence for reducing inflammation
• Stress management – Stress can worsen symptoms
Next Steps Before the GP Appointment
1. Get Liver Function Tests (LFTs)
• If not already done, recent ALT, AST, ALP, Bilirubin, GGT results can guide treatment decisions.
2. Check if Thiopurine Methyltransferase (TPMT) or NUDT15 Testing Was Done
• These tests predict how a person metabolizes 6-MP and azathioprine.
3. Consider Requesting a Fecal Calprotectin Test
• If they haven’t had one recently, this can help assess inflammation levels.
4. Look into Available Biologics
• If switching is needed, it’s worth reading about biologics and whether NHS guidelines allow direct switching.
What to Discuss with the GP
• Do I need an urgent consultant referral?
• If liver damage is significant, they should push for an expedited gastroenterology appointment.
• What are my options?
• Ask whether to try methotrexate, biologics, or JAK inhibitors based on their case.
• Should I stop 6-MP immediately?
• If the liver is significantly affected, stopping 6-MP right away may be necessary, but this should be done under medical supervision.
• Do I need further liver tests (ultrasound, elastography, etc.)?
• If there’s concern about chronic damage, an ultrasound or FibroScan may be needed.
Final Thoughts
The best next step depends on how severe their Crohn’s is, past treatments, and how badly the liver is affected. If it’s urgent, they should call their IBD nurse (if they have one) or request an earlier appointment. If NHS waiting times are too long, they could consider private gastroenterology consultation to expedite treatment.
@fentonsteve
Have you had anti-TNF therapies previously (ie the four listed above, starting with infliximab)?
Not yet.
So far: lots of steroids, Azathioprine (which my body rejected fairly quickly) and 6-MP which I have been on for nearly 9 years, and “functioning” for about 7 or 8 of them.
Currently: nothing, until bloods show my liver has recovered.
I quite like functioning, in my limited way. I really don’t want to go back to being ill!
Personal experience. I am in the process of switching medications. Have been injecting myself weekly with Humira for 9 years, but it seems to not be effective any more. Have been quite poorly since before Christmas.
They are going to try me on Rinvoq which will be one pill a day taken orally. My insurance provider needs to approve it as it is costly (less than Humira though I think) and I am having various tests before I can start. Yesterday I had blood work to check if I have latent TB or Hepatitis as my immune system will be affected. Last time I was positive for TB and had to take a certain antibiotic for almost a year to sort that out before I started on Humira. I also need a shingles shot.
I am glad I won’t need to inject myself any more hopefully although Humira was the best thing I have been on. Really helped me for most of those 9 years.
Just started on steroids to hopefully quickly remove current inflammation before I start the new thing in a few weeks
Good luck finding the right thing. I have also heard Entyvio can be good. I believe that is injected periodically or from an occasional IV.
Crikey, that sounds like a palaver.
Does injecting yourself with Humira draw red stuff? I am hopeless with needles. When I was anaemic, I was supposed to prick a fingertip, get some into a little jar, and stick it in the post to be analysed. I passed out after one drop, much to the amusement of Mrs F, and went down the GP surgery to have it extracted by a nurse while I looked at the ceiling.
No red stuff, fairly easy to do (Epi-pen) takes about 10 seconds, hurts a little. Glad not to do it any more though
Very fine needle – as pain-free as they are able to make it.
And definitely no red stuff – listen to your Uncle Dai…
I don’t mind a bit of pain so much, but the site of, erm, ketchup, brings on wobbly eyeballs and tweety birds flying around my head.
When I am having blood work done which is pretty often I look in another direction
Any of the -imab agents. Seem to be game changing, usually far better tolerated than the old traditional poisons.
Do they have the same side-effects? Nothing disabling, but being UV hypersensitive is a pain, so Mrs F can’t go on any sunny holidays, and I have various itchy and blotchy patches (including one side of my nose).
Sides tend to be more idiosyncratic to the individual than by expectation, and of the sort that are picked up more by blood test, from what I recall. As in inflammatory markers more than by spots or rashes.
Those who take them can answer better than I, mind, plus I’m nearly a year retired, and off the register.
I, too, think biologics are your best bet, steve.
Thanks, both. I will steer conversation with my consultant in that direction when I get my follow-up.
All the above is great advice and I dearly hope you get the best new treatments, Steve. However, I’m not sure ‘boning up’ is what you require right now…;-)
Can you shout out of your window and tell Moose we need him back? I keep leaving him breadcrumbs…
Well, we’re both from Hull…must be summat in t’Umber.
Another vote for biologics, I’ve been with Imraldi (Adi..bab) for a couple of years now after 6-MP tried to kill me.
Good luck, mate.
Azathioprine tried that with me. I think I glowed in the dark when I was on it.