Another question....sorry 😬

[Am1025]

Hello again!

As a lot of you have probably seen, my husband is set to start Humira (whenever insurance ok's it, it's been a nightmare to get it approved between the doc office, it's been 2 weeks...... etc anyway) his GI doc wants to keep him on mercaptopurine for 2 years along with Humira. Neither one of us are super comfortable with that idea and we are going to ask if he can taper off the mercaptopurine and track his antibodies and then add something in IF he starts to build antibodies. His aunt (crohns also) has done Humira only for 15 years and never had an issue and has been in remission except 1 minor flare ever since. But his doc acts like while he doesn't "have to" he would like him to and says it lowers the risk of antibodies, but my research seems to show that as being a little more old school. Obviously we will be discussing this with his doc whenever he goes in for his loading dose and I know the mercaptopurine will have to be weaned down, not cold turkey. But any feedback would be greatly appreciated. Thanks so much!

 

[my little penguin]

Get a second opinion from another gi at another university based hospital .
6-mp/imuran isn’t something you wean at all
It can be stopped or started whenever
So please talk to your husbands Gi about that
Second
Most studies show that you can take 6-mp with humira at first (6 months ) then stop to prevent antibodies to humira
Once you have developed antibodies -then it is harder to get rid of the antibodies
The medicine then either stops working or you have a reaction
No way to predict who will get antibodies
6-mp or methotrexate lowers that risk

most pediatric docs combine with methotrexate and humira for antibody reduction

The extra risk with 6-mp and humira combined is still there especially if you took 6-mp prior to biologics
Combining with biologics with 6-mp raises the risk of T cell lymphoma but that was in young males .

 

[Am1025]

Get a second opinion from another gi at another university based hospital .
6-mp/imuran isn’t something you wean at all
It can be stopped or started whenever
So please talk to your husbands Gi about that
Second
Most studies show that you can take 6-mp with humira at first (6 months ) then stop to prevent antibodies to humira
Once you have developed antibodies -then it is harder to get rid of the antibodies
The medicine then either stops working or you have a reaction
No way to predict who will get antibodies
6-mp or methotrexate lowers that risk

most pediatric docs combine with methotrexate and humira for antibody reduction

The extra risk with 6-mp and humira combined is still there especially if you took 6-mp prior to biologics
Combining with biologics with 6-mp raises the risk of T cell lymphoma but that was in young males .

Sorry I should have specified, I meant weaning as in I know Humira takes about 3 months to build up in your system. What do you mean by extra risk? He's been on mercaptopurine for almost 5 years. That concerns me.

 

[my little penguin]

Abstract
Background & aims: Thiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk of lymphoma in patients with IBD exposed to thiopurines and compared relative risk values derived from population-based studies with those from referral center-based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma.
Methods: We searched MEDLINE, EMBASE, and Cochrane databases, as well as conference abstracts and international publications, for the terms "6-MP and lymphoma," "6-mercaptopurine and lymphoma," "thiopurines and lymphoma," "azathioprine and cancer and IBD," "azathioprine and malignancy and IBD," "azathioprine and lymphoma," and "lymphoproliferative and thiopurines." Pooled standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated. The deviance statistic from Poisson models was used to calculate heterogeneity.
Results: Eighteen studies (among 4383 citations) met our inclusion criteria. Overall, the SIR for lymphoma was 4.92 (95% CI, 3.10-7.78), ranging from 2.80 (95% CI, 1.82-4.32) in 8 population studies to 9.24 (95% CI, 4.69-18.2) in 10 referral studies. Population studies demonstrated an increased risk among current users (SIR = 5.71; 95% CI, 3.72-10.1) but not former users (SIR = 1.42; 95% CI, 0.86-2.34). Level of risk became significant after 1 year of exposure. Men have a greater risk than women (relative risk = 1.98; P < .05); both sexes were at increased risk for lymphoma (SIR for men = 4.50; 95% CI = 3.71-5.40 and SIR for women = 2.29; 95% CI = 1.69-3.05). Patients younger than 30 years had the highest relative risk (SIR = 6.99; 95% CI, 2.99-16.4); younger men had the highest risk. The absolute risk was highest in patients older than 50 years (1:354 cases per patient-year, with a relative risk of 4.78).
Conclusions: Compared with studies from referral centers, population-based studies of IBD patients show a lower but significantly increased risk of lymphoma among patients taking thiopurines. The increased risk does not appear to persist after discontinuation of therapy. Patients over 50 have the highest absolute risk of lymphoma per year on thiopurines, while men under 35 may also be a high risk group. More study is needed to precisely understand groups highest at risk. The risks of lymphoma and potential benefits of therapy should be considered for all patients with IBD.

https://pubmed.ncbi.nlm.nih.gov/24879926/

 

[my little penguin]

Hepatosplenic T-Cell Lymphoma and Anti-TNF Therapy
A more well-supported association between IMM use in IBD and malignancy development is that of hepatosplenic T-cell lymphoma (HSTCL), a rare malignancy with rapid progression and high mortality rates. HSTCL has been associated with IFX, ADA, and, primarily, TP use.34 In 2011, Kotylar et al used the FDA Adverse Event Reporting System (AERS) database to assess the risk of HSTCL with ATA use.37 Of the 36 subjects diagnosed with HSTCL, 16 were on TP monotherapy and 20 had both TP and ATA exposure. Median time from start of TP therapy to diagnosis of HSTCL was not statistically different between combination therapy and TP monotherapy at 5.5 and 6 years, respectively. Further review in 2019 found that the risk for HSTCL was indeed related primarily to TP use.38 The risk has also been attributed to dual therapy, especially if used for longer than 2 years.36

A 2020 study also examined data from the FDA AERS database.39 Patients were divided into combination therapy, biologic monotherapy, or no biologic therapy groups. Sixty-two cases of HSTCL were identified from 2002 to 2017 with the majority of patients being male (83.6%), young (median age 28 (range 12–81)), and having Crohn’s disease (84.7%). All affected patients had received at least one dose of a biologic (ATA, IL 12/23, or integrin inhibitor). Fifty-seven patients had azathioprine or mercaptopurine exposure. The five patients who had no history of TP use had IFX exposure. The authors argued that, despite the appreciated correlation with TP use, there still may be an associated risk with ATA.39

The study also assessed the role of EBV in HSTCL development. Only 4 of the 62 cases were found to have active EBV infection. Therefore, the role of EBV in HSTCL remains unclear. While HSTCL is a serious illness with poor outcomes, the rarity of developing this malignancy should be weighed against the higher risk of worsening or uncontrolled IBD when considering ATA therapy.39

From
https://www.dovepress.com/risk-of-l...s-with-inf-peer-reviewed-fulltext-article-CEG

 

[Am1025]

https://pubmed.ncbi.nlm.nih.gov/24879926/

Ugh that gives me extreme anxiety especially since idk when he will actually start the humira

 

[my little penguin]

They do NOT use 6-mp anymore in pediatric crohns due to the increased lymphoma risk- most tend to use methotrexate instead .

pediatric Gi’s will NOT combine 6-mp/imuran with biologics in young males patients due to the increased risk of fatal Tcell lymphoma in that group
They use methotrexate to combine with biolgics instead

 

[Am1025]

They do NOT use 6-mp anymore in pediatric crohns due to the increased lymphoma risk- most tend to use methotrexate instead .

pediatric Gi’s will NOT combine 6-mp/imuran with biologics in young males patients due to the increased risk of fatal Tcell lymphoma in that group
They use methotrexate to combine with biolgics instead

All that made me nauseous. I seriously am scared now. He's been on it for 4.5 years. Makes me want to have him come off now.

 

[my little penguin]

Fwiw my kiddo was on 6-mp for 8 months at age 7-8 before they knew about the risks
He then used methotrexate for three months before moving on to remicade
So the risk was there for him at an early age
10 plus years later (18 now )
No issues
He is on Stelara plus methotrexate (4 plus years)
And was on humira plus methotrexate a for 5 plus years

 

[my little penguin]

Ibd all by itself raises risk of cancer
Uncontrolled ibd definitely raises the risk
So keeping it under control is key
Adding humira is great
Some need bridge therapy (steriods or formula only )
BUT steriods have their own sets of risks
Even infant Tylenol can cause death ,liver failure or Steven Johnson syndrome but it’s used every single day o. Babies
My point
Lots of risks are taken by us every day
Just get to a med that keeps things calm
As quickly as possible
That’s all you can do
And hope for the best

 

[Am1025]

Ibd all by itself raises risk of cancer
Uncontrolled ibd definitely raises the risk
So keeping it under control is key
Adding humira is great
Some need bridge therapy (steriods or formula only )
BUT steriods have their own sets of risks
Even infant Tylenol can cause death ,liver failure or Steven Johnson syndrome but it’s used every single day o. Babies
My point
Lots of risks are taken by us every day
Just get to a med that keeps things calm
As quickly as possible
That’s all you can do
And hope for the best

Well ill have to tell myself, he's not under 18 of over 50 and those 2 age groups seems to fair the worst and I've talked to some that have used mercaptopurine for 20 years or so with no issues and That's pretty much what his doc has always said too, that they aren't totally sure if it's medication alone that causes the risk, having IBD, having uncontrolled IBD or all together. To pick the lesser of the evil, which uncontrolled disease is deff the bigger evil and his doc has always felt like all of the meds carry risk. Even now, he has some active disease but his inflammation markers are great so are his white cells and such. My MIL has R.A. and has tested positive for Crohns and she's on Cimzia, Cyclosporine and MTX as well as some other one I'm missing. So her risk is much higher and she's been fine. I keep telling myself to not worry, but as you know. That's not always easy. We are getting a 2nd opinion though. I appreciate your time!