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Crohn's Disease Forum » Books, Multimedia, Research & News » Study shows anti-TNF drugs don't increase cancer risk


01-14-2014, 06:42 PM   #1
nogutsnoglory
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Study shows anti-TNF drugs don't increase cancer risk

"Use of anti-TNF drugs such as infliximab do not raise the risk of cancer in Crohn’s patients, say US researchers.
Data from over 6,000 Crohn’s patients from the TREAT registry showed that neither infliximab alone, nor immunosuppressive therapy alone, nor a combination of the two was independently associated with the risk of later cancer.
However disease duration, age and smoking status were all positively linked to cancer risk, the researchers from the University of Pennsylvania found."

http://www.gastroenterologyupdate.co...nked-to-cancer
01-14-2014, 06:57 PM   #2
Tesscorm
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Thanks NGNG for posting!

Here's a bit more detail from the same study.


Drug Therapies and the Risk of Malignancy in Crohn's Disease: Results From the TREAT™ Registry

Gary R Lichtenstein, Brian G Feagan, Russell D Cohen, Bruce A Salzberg, Robert H Diamond, Wayne Langholff, Anil Londhe and William J Sandborn

Abstract
OBJECTIVES:

We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined.

METHODS:

Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, infl uences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confi dence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA).

RESULTS:

As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither.

CONCLUSIONS:

In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.

http://www.nature.com/ajg/journal/va...g2013441a.html
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01-14-2014, 07:21 PM   #3
kiny
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Shouldn't use titles like that to be honest. A single study is a single study, not a fact. There are continuous studies regarding immunosupressants and many that contradict that study.

I don't think it's good to just link one single study and then make a title like that. There have been many that showed an increased risk, there have been some that did not. My guess is that there is probably an increased risk based on the volume of studies that do show an increased risk.


The question should also be asked, what happens to someone who is on TNF-alpha blocker and gets a cancer. Not just onset matters. People on TNF-alpha blockers who get cancer, especially combo therapy, often have rapidly progressing cancers, because of the fact they were on TNF-alpha blockers.


TNF-alpha stands for Tumor necrosis factor alpha, it didn't get that name by accident, it's directly involved in killing of cancers.




http://www.ncbi.nlm.nih.gov/pubmed/24328939

Melanoma Associated with TNFα Inhibitors: a Research on Adverse Drug events And Reports (RADAR) Project.
Nardone B, Hammel JA, Raisch DW, Weaver LL, Schneider D, West DP.

2013 Dec

BACKGROUND:

Tumor necrosis factor-alpha inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, "melanoma has been reported in patients treated with these agents."

OBJECTIVES:

Determine whether a statistically-significant association exists between administration of TNFαIs and development of malignant melanoma.

METHODS:

We searched the FDA Adverse Events Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. non-exposed subjects.

RESULTS:

There were 972 reports of melanoma associated with a TNFαIs identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab (I) golimumab (G), etanercept (E), and adalimumab (A). Cetrolizumab pegol (CP) had no detectible safety signal. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6,045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for A (RR = 1.8, p = 0.02) and E (RR 2.35, p = 0.0004).

CONCLUSIONS:

We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to further explore this association and the risk of melanoma with TNFαI therapy.

Last edited by kiny; 01-14-2014 at 08:05 PM.
01-14-2014, 08:58 PM   #4
nogutsnoglory
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Kiny, that's why I wrote "study shows" because it's far from a fact but at the same time it's an encouraging and exciting piece of large research. We deserve a little hope?
01-14-2014, 09:32 PM   #5
kiny
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Yes we do. I'm just saying that people should still be careful with things like sunlight on TNF-alpha blockers and imuran, etc. Imuran carries warning labels about that. My guess is that there is an increassed risk, it just isn't apparent in every study.
01-14-2014, 09:34 PM   #6
Tesscorm
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Much of what I've read about anti TNFa is just plain way above my head , so this may be a 'basic' question but ...

My understanding is that the biologics block or inhibit the actions of TNFas, right? If yes, is the impact cumulative? Are there studies that show your risk of developing cancer increases as a direct result of prolonged use of anti-TNFs. Aside from the fact that if you are on a biologic for one year, you have one year's chances opposed to being on for five years so five years worth of chances (with the chance being equal each year). So, is your risk of cancer higher in year 5 than in year 1 - hope I'm making sense??

Also, once you stop using a biologic, does your risk of developing cancer return back to the same risk as the general public?
01-14-2014, 09:47 PM   #7
kiny
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TNF-alpha is a signaling cytokine, it's like a director from an orchestra. Immune cells have ways to communicate with one another, they can present antigen to one another, during an immune response for example, cells put parts of the antigen (antigen could mean bacteria here) "out there" so other cells can interact with it. When an APC, antigen presenting cell, goes into the lymphatic system, it causes an adaptive immune response, T Cell, NK cells, B cells in the lymph system set off the alarm once they see the APC signal and they cause thousands of cells to home in on the target and you get inflammation.

To make sure all those reactions runs smoothly, you need directors, signaling molecules, TNF-alpha and interleukin, they need to orchestrate everything. They don't really understand what they all do, they don't really understand why infliximab works. It might be because when infliximab binds to TNF-alpha, part of the response is lessened, maybe it's an anti-microbials because some bacteria exploit an inflammatory environment, maybe it's because it's causing apoptosis of certain immune cells, they're not sure.

Why one would assume that if you lower TNF-alpha, your chance of cancer increases, is because you're interfering with an important orchestrator, you're breaking signals that are needed to not only control bacteria, but also cancers.

Everyone has "potential cancer cells" in their body.....but most just get destroyed by our immune cells before you even notice they're there.
01-14-2014, 09:53 PM   #8
kiny
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I should also say something about the lymph cancers that people fear. They are seen especially in children in combo therapy.

The reason for this is specifically attributed to the use of the TNF-alpha blockers.

You have a certain number and type of lymphocytes in your body. You have T cells, B celll, and within those types you have CD4, CD8, etc.

If you cause a decrease in certain lymphocytes, and someone already has a big number of malignant lymphocytes, you can easily increase the percentage of malignant lymphocytes if you use immune modifying agents. Which explains why some got lymph cancers and why that cancer is specific for TNF-alpha blockers for some people. Extremely rare.
01-14-2014, 09:54 PM   #9
nogutsnoglory
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I think another piece of the puzzle that needs to be questioned is what's the cancer risk for those with IBD not on anti-TNF's? We are at an increased risk just by the nature of the disease and I wonder if other research disproves this study if weighing it all that those on these drugs fair better cancer wise.
01-14-2014, 09:57 PM   #10
kiny
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Also, once you stop using a biologic, does your risk of developing cancer return back to the same risk as the general public?
I don't think anyone knows that. If you look at imuran, imuran increases the risk of skin cancer for people who are in the sun a lot, and that risk does decrease once they go off imuran. You're asking if you just "undo" everything and everything gets simply reset, I think the immune system is much too complex to know that.

That the risk decreases once you go off immune modulators is probably a given.
01-14-2014, 09:58 PM   #11
kiny
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I think another piece of the puzzle that needs to be questioned is what's the cancer risk for those with IBD not on anti-TNF's? We are at an increased risk just by the nature of the disease and I wonder if other research disproves this study if weighing it all that those on these drugs fair better cancer wise.
Chronic inflammation in itself probably increases the risk of cancers. It's a good question.
01-14-2014, 10:01 PM   #12
Tesscorm
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Thanks so much!!! Your explanation actually makes it all make sense now!

So, in my mind, that means your risk of cancer in 5 years would be the same as in year 1, for example. As remicade (like almost all meds) need to be re-dosed, I'm assuming the impact wears off, ie, in remicade's case, it only blocks the TNFa for a time period and more must be re-injected to maintain the blockage/inhibition of the TNFa. Am I on the right track?
01-14-2014, 10:09 PM   #13
kiny
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Well, all immune cells are regerative, they take a while to grow and mature. They're very complex and they learn from each other. Some exist days, others exist for months. Some are very busy and constantly moving around in your body, some like macrophages line your intestine and just wait in tissue until something happens

Some like B cells, can be generated by the thousands per second.

It's complext to say what would happen if you lower a signaling molecule.

.
.
I think what you're asking is, is it cumulative or not, if you take more infliximab, does your risk keep increasing. Your risk wouldn't keep increasing just because you use it longer....not all TNF-alpha gets removed.....there are many ways for your body to deal wtih cancers, it has a whole toolbox.....TNF-alpha gets restored......infliximab does not stay in the body, it has a halflife of a few weeks. You are at risk when you take it, but it's not that the risk keeps increasing no.
01-14-2014, 10:12 PM   #14
Tesscorm
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Thanks Kiny for your explanation - much appreciated!
05-18-2014, 03:16 PM   #15
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I was on remicade for many years in "remission" and no steroids for the first time in many many years. Worked great then I started having symptoms after about 8 years so My GI increased the dosage which helped a little. Except I got 3 squamous cell skin cancers first cancers ever and I am n my 60s.
We reduced the remicade. Turned out I now also had collagenous colitis and that what was causing the symptoms
Then the remicade no longer worked GI retired and now the new guy put me on humira, entocort pred, and I developed a PA fistula and now also on cipro, clindomycin.cant take flagyl. Humira doesn't seem to do much. If this fistula doesn't heal I may stop the humira get a baseline and try remicade again. My Only symptom now is the fistula but it took pred on my suggestion to control the inflammation in my rectum and the antibiotics helped all around. Doc kept saying give humira time I did it didn't help but the pred did. Entocort doesn't work in the rectum.

I think it is really important for all of us IB people to eat really healthy organic pesticide free simple unprocessed foods and take heavy anti oxidants like resveratrol and astralagus as all the immune suppressing drugs probably make us all more susceptible to the environmental carcinogens we are exposed to.
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05-18-2014, 05:17 PM   #16
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Robrich: Remicade is something you build up antibodies to, so you likely can't go back on it. You would probably need to try another biologic. That's unfortunate about the Humira, though... it's done wonders for my fistula. Is it still draining? Do you still have a seton in?
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05-18-2014, 06:48 PM   #17
Robrich
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Ocean thanks for the reply. Yes it is still draining dodged the seton.
It's not very active or as bothersome as it could be. Still hoping the current regimen will heal it. Only been 2weeks on the antibiotics. Remicade was a miracle drug for me in that respect.
Not sure if I built up antibodies or it stopped working for other reasons, but you are probably right. I should get that tested at some point. I am more hopeful hearing humira cleared up your fistula. But with 5 months of humira and it was the pred that got the inflammation under control. Maybe cimzia then or hold on for the next new treatment
However one thing I have learned in 50 years wth this is don't assume anything and especially don't be tied down to any current protocol as they constantly change and every case is different, almost, anyway?
05-18-2014, 06:57 PM   #18
theOcean
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Ocean thanks for the reply. Yes it is still draining dodged the seton.

It's not very active or as bothersome as it could be. Still hoping the current regimen will heal it. Bly been 2weeks. Remicade was a miracle drug for me in that respect.

Not sure if I built up antibodies or it stopped working for other reasons, but you are probably right. I should get that tested at some point. I am more hopeful hearing humira cleared up your fistula. But it 5 months of humira and it was the pred that got the inflammation under control. Maybe cimzia then or hold on for the next new treatment

However one thing I have learned in 50 years wth this is don't assume anything and especially don't be tied down to any current protocol as they constantly change and every case is different, almost, anyway?

I've had my fistula since late last May, and was originally treated with Remicade, Imuran and Cipro/Flagyl after my fistulotomy. I was allergic to Remicade and switched to Humira in November, and within one-two months all drainage had stopped for me, and then three weeks ago I finally got my seton removed and the fistula has been closing and healing. I also stopped cipro/flagyl after eight months in December. The addition of an immunosuppressant might help you but ultimately I think biologics are best. It may also help to increase the frequency of your Humira dosage - I inject once every week, which I think really makes a difference.

It's true pretty much everyone's experience is different, though. I hope you find something that works for you!
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