00:00:00: Hello, everyone.

00:00:00: Good morning!

00:00:01: Welcome to another episode of the UAG podcast.

00:00:04: it's Pradeep Pundray here.

00:00:06: my guest controls us from the UK and podcast host for The UAG.

00:00:11: The weather is changing these days a brilliant spring coming up with most of us I'm assuming so.

00:00:16: today we move on to bit about IBD and IBD management which has become more and more complicated With a plethora new drugs And different targets of treatment.

00:00:29: Most of us and patients alike have increasing access to these new drugs.

00:00:35: So lately, the use of these drugs in complex patient situations is increasing And we come across this on a day-to-day basis.

00:00:42: A couple special situation that I can think off Is those patients who've had previous cancers Now in remission Those patients with active malignancy.

00:00:54: They need active management of their IBD whether these are aggressive type cancers or slow growing cancers.

00:01:01: These are all few different case scenarios that not easy to deal with and sometimes need decision making probably in an MDT setting, but some of us we're left on our own to make decisions along without patients And it may be a bit confusing for both clinicians the decision makers and patient.

00:01:17: Sometimes you put forward some statements to the patience and then its difficult For Both Of Us To Make That Decision And today's discussion with our guest is on this scenario, we'll be discussing about cancer risks in IBD or whether that disease related itself for how IBD therapies influence malignancy risk.

00:01:37: Whether they increase or decrease?

00:01:39: We can talk about them and will also discuss about safe use of IBD treatment in patients with past and present history.

00:01:47: For the purpose of this particular episode, we will not delve into IBD-related colorectal cancer.

00:01:55: The reason being that's a huge topic altogether and I would purposely leave that aspect out at the discussion today And we'll probably have its own podcast for that.

00:02:07: Todays guest is Dr Hannah Gordon who was a consultant gastroenterologist at University Hospitals Oxford in the UK.

00:02:15: Hannah was the project coordinator and lead author for The Echo Guidelines on IBD and Malignancy, which was published a couple of years ago.

00:02:25: Hannah is also co-authored as part of the guideline committee for various other guidelines including the echo therapeutics in Crohn's guidelines or the latest BSG IBD guidelines are welcome to the podcast.

00:02:40: Thank you so much for inviting me, Pradi.

00:02:42: It's sunny in Oxford here as well and it's a beautiful change to the weather.

00:02:46: and welcome back from Morocco!

00:02:48: I totally agree with you that this is an area we see more of who are living or have survived previous cancer.

00:03:00: At the moment, I think about one of three of our IBD patients in the clinic is over sixty and with an ageing population this will only grow.

00:03:08: So we almost have to stop seeing when IBD and cancer collide as a special situation but unfortunately see it part-of life because that's something very commonly managed.

00:03:23: get nervous about such patients and then put them through the MDT and things.

00:03:27: But I guess with more knowledge that we have, guidelines like yours would really help us manage these situations because IBD-MDTs will be overburdened by lots of this complex patients.

00:03:40: You're totally right, I'm not suggesting that we don't discuss in the MDT just more than it's becoming more and more common but you are really right.

00:03:47: The first ECHO malignancy guideline was suggesting patients who had cancer before should be on most immunosuppressive therapies or then biologics advanced therapy for between two to five years after the resolution of their cancer, and I think this brings concerns is that since that era we know that treating IBD effectively is really important.

00:04:14: And recurrent causes of steroids, recurrent disease flares isn't good for patients either.

00:04:20: Hannah, let's start with the first point of discussion.

00:04:23: I just wanted to start overall in patients?

00:04:39: I think so.

00:04:39: You've asked me to stay largely away from the more well-known areas such as colorectal cancer, which is an established risk with established screening pathways and even multivariate risk calculators.

00:04:51: PSC is another obvious known area where there's a high enough malignancy risk that we have established ways in which we mitigate both the colorextal cancer.

00:05:05: One of the more pressing areas, or in difficult areas is when there isn't increased risk but absolute risk still relatively rare and how we mitigate that.

00:05:17: I mean an example i could give with that are small bowel cancers for patients with small bowel disease.

00:05:29: There's definitely an appreciable relative risk compared to other populations but the absolute risk is still quite low.

00:05:38: I think when we were doing the malignancy guidelines, that systematic review we undertook showed papers that were quoting risks within the remit of sort-of twenty five patients per a hundred thousand patient years and these are numbers that i think even as doctors it's quite hard for us to get our head around.

00:05:56: so whereas communicating at risk two patients then when its appropriate communicate because you want the balance.

00:06:03: You want a really informed, empowered patient actively involved in their own decisions but you also don't want a terrified patient who every time they come to clinic is being told about the risk of another cancer and other cancer when the absolute risk is much lower than other cancers that we do not have population screening for with general populations.

00:06:23: so I think it can be a tricky balance.

00:06:25: Another area which puts fear into us risk of perianophysiola cancers, risk of rectal stump cancers in patients who have elected not to undergo proctectomy or pouch formation.

00:06:39: And yes these are areas that we worry about.

00:06:43: but sometimes surveillance is difficult.

00:06:46: in the context of the rectal-stumped surveillance –the practicalities of surveying an area of bowel with diversion colitis–is challenging but also the intensity of, for example coming back to the small bowel cancer case which I know when we were prepping this you are quite interested in talking through sort of logistics and reality whether or not we undertake routine MREs.

00:07:09: well-patients with small bowel chronicies.

00:07:11: When absolute risk is pretty low?

00:07:14: Okay so against language that they have all different conditions some of us like to coat.

00:07:23: Some of them like to use sort-of loose terms such as, oh there's a high risk.

00:07:26: There is low risks and this is negligible.

00:07:29: overall I think the language that we used our patients are important in their select whatever risk that you mentioned.

00:07:34: they're really not my own mind.

00:07:36: i'm very confused.

00:07:37: you know he said hello what is it?

00:07:40: What do you say?

00:07:41: there is the kind of language that these other patient is important.

00:07:45: so my conclusion or based on that There is a slightly increased risk of cancers, solid organoanalgenic disease and other malignancies in patients with IBD irrespective off the drugs or irrespectful therapy they're on.

00:08:04: However this risk is very low.

00:08:08: Is that what you getting at?

00:08:10: I think for most cancers That's true And i also thing when we convey things to our patient it important with purpose.

00:08:19: I mean when we talk about for example the colorectal cancer, we're letting them know and we're letting them know of a surveillance program and symptoms to watch out for and i think we need to take that in mind when we decide we communicate.

00:08:30: for any other forms of cancer...I mean especially in terms of this small bowel stricturing patient where there isn't necessarily an established surveillance pathway A lot of onus is on the clinician, I mean we're asking patients to report symptoms to us.

00:08:46: To getting touched by the IBD advice services which aren't necessarily at a first pass so different from symptoms that you would necessarily see with active small bowel or structuring small bowel Crohn's disease.

00:08:59: I wonder if, as clinicians for us it's something that we just need to consider in the back of our mind.

00:09:04: If something doesn't look quite right?

00:09:05: To involve the GI radiologist... ...to involve the MDT and make sure that we keep it in our minds of a differential when planning timing investigations….

00:09:14: …and how we follow up with tests with

00:09:16: patients.".

00:09:18: I guess, it's important for us clinicians and patients alike to have that knowledge.

00:09:24: Let say if I develop a new symptom or whatever then at least we are patient.

00:09:29: all clinicians take appropriate action but investigate them promptly.

00:09:33: having the knowledge helps.

00:09:35: i think thats important.

00:09:36: yeah excellent.

00:09:38: Now moving on to IBD drugs and I guess we can go through different classes here Hannah.

00:09:44: In the past, I think you know most IBD Drugs were labeled as being bad in terms of malignancy risk and things.

00:09:50: maybe we should go through that... Maybe we may want to go through it class by class.

00:09:54: uh ...in terms of what IBD drugs are implicated or maybe even i call it associated with increased risk of maligency.

00:10:02: I want to choose my words carefully here because its causality is different from link or association.

00:10:09: So if you kind of maybe go through class by class, explain it for us?

00:10:12: Yeah

00:10:13: so i think what your saying absolutely right.

00:10:17: there's an association with some drugs that not always in all cases proving a causal relationship and needs to be interpreted accordingly especially when we know that active IBD is itself a risk certainly for colorectal cancer or certainly active colonic IBD as a risk of colorector cancer and kind of interpreting the relative risks and benefits.

00:10:39: But what I think it's interesting now, as we have more choice in more options before a risk for thypeurins ,for example .

00:10:49: And i'll come on to talk about little bit more as a relatively low risk compared with the benefits of the drug.

00:10:58: Now that we have different drugs available, it's little bit more nuanced discussion or thought point.

00:11:06: also now that we're keeping patients on maintenance therapy be that advanced therapies are otherwise for longer periods time kind cumulative risks comes into our decision factor.

00:11:17: going through Drugs class by Class starting I don't think that i know of any cancer associated risks with steroids, with exclusive enteral nutrition or with mesalazine.

00:11:35: Coming through and i'm going through kind of the timeline of when these drugs became widely available to us-I'm not picking them for any other reasons.

00:11:42: now The thiopurines is an interesting one because there is a recognized increased relative risk big groups that I think are relatively certain.

00:11:53: there is an association, one being hematological malignancy.

00:11:57: The other be non-melanometer skin cancer in particular squamous cell carcinoma of the skin.

00:12:03: so thinking mainly of the hematologic risks because i think this is what we fear and worry about.

00:12:09: .I'm going to say first and foremost I am aware that absolute risk it low.

00:12:14: ,the relative risk seems highest when used with an anti-TNF and in young men, especially those who have not been exposed previously to EBV.

00:12:28: The absolute risk is higher in older people because the absolute risk of all cancers is higher than older people.

00:12:36: And I believe if you're using a thipurin as monotherapy by the time you get sort of between sixty to seventy... ...and these are ballpark figures.

00:12:46: about One in two hundred patients per year may develop a dipurin-related cancer and these stats do differ depending on the different cohorts.

00:12:57: For me, what I take home from that when using dipurins... And again there is no textbook or clear consensus on how we all interpret risk.

00:13:07: Is it for me?

00:13:08: ...for young patient especially if they've not being exposed to Epstein-Barr virus, I think is this the right choice of drug for them?

00:13:17: Is there another option in Crohn's disease.

00:13:20: I tend not use the thyperins as a monotherapy because i don't think they work very well but if im using them as combination therapy with an anti TNF therapy After a year, I think that they need to be on both and in the majority of patients.

00:14:00: relative risk, probably compared with other drugs that you could use as an alternative.

00:14:07: So for me personally I don't tend to use them but i do think particular areas where we all should be starting to worry a bit more about life here in risk is in the older patient cohort sort of over sixties or people who have got accumulative exposure to them above seven or eight years which was when Do they definitely need to be on the drug and is there a safer alternative?

00:14:33: And that, Is There A Safer Alternative question may depend locally on finances ability to provide drugs.

00:14:41: That are maybe less cost effective for other viperians and the patient journey of the individual patients does not make sense.

00:14:49: Yeah, I think i got the overall gist.

00:14:52: So over all we agree that there is ever so slightly increased risk of malignancy in patients exposed to typerin which was mainly lympho-proliferative disorders.

00:15:02: and you mentioned EBV.

00:15:03: can just clarify on that?

00:15:04: Just for the sake of the registrar's can you clarify so EBV status?

00:15:09: you would check by checking their IgG if they are positive.

00:15:14: So if they're positive, they've been exposed to it before.

00:15:17: I'm not too worried about this in context of a thypurein If someone has never had mono-glandular fever EBV and the developer was on a thyroid purine there's a reasonable risk of developing a significant post-monomucleus hematological malignancy things like the hepatic splenic T cell lymphomas which once did.

00:15:41: this is rare.

00:15:43: If it's an avoidable consequence, its pretty tragic when it happens.

00:15:46: So that is why my practice would be to screening for EBV and also judicious use of the thiopyrins.

00:15:55: Yeah!

00:15:56: And this such a simple test because you are sending them other serology anyway.

00:15:59: so just add on an EBV too.

00:16:02: then there will be more I guess more cautious think alternatives if they're EBV naive or Serology negative.

00:16:12: Okay, that's clear.

00:16:15: And you mentioned that a combination therapy with anti-tenants increases the

00:16:19: risk.

00:16:20: Yeah, I think it.

00:16:21: just briefly on that one.

00:16:22: I think anti-TNF itself as a risk for malignancy.

00:16:25: there's small signals That may be a risk from melanoma is more especially in Crohn's disease but less so an osteoarthritis.

00:16:32: There's a small signal that the that the entity and F itself maybe a risk.

00:16:36: behemothological Malignancy although It's not always replicated or in all cohorts But when they combine together at their risk becomes more significant.

00:16:45: And I think that kind of makes sense.

00:16:46: if we're thinking a lot the hematological malignancies may in some way be virally driven, it would make sense that a combination immunosuppression might impact that.

00:16:54: but just for any patients or anyone listening again i will stress that absolute risk is low and needs to be balanced with risks associated.

00:17:05: Yes, I think that's probably there.

00:17:06: There is a huge risk of under treating the disease in most scenarios as common theme than I see.

00:17:16: moving on to newer drugs any new drugs implicated?

00:17:20: This

00:17:21: is this is a reasonably easy one-to-one.

00:17:23: so i think in the sense that the meta analysis data and post marketing data from vedalizumab suggests it safe.

00:17:30: no overall increased risk for any malignancy.

00:17:34: Earlier on in the use of vetylizumab we were maybe worried that we might see more colorectal dysplasia and colorector cancers because, in theory you might be reducing immune surveillance at the gut.

00:17:44: Because not only are we preventing the proactive inflammatory T cells from coming into the gut but that mechanism is quite conserved amongst other cell types as well.

00:17:53: But fortunately we've now been using Fetalizumab, I believe from just over ten years and none of the data that i'm aware of has shown any adverse signals in that area.

00:18:04: So in general this can be thought as a relatively safe option but not aware for us to kinemab being associated with malignancy either in the IBD population or in the psoriasis registries from dermatology.

00:18:21: And similarly, there's less data available for the P-nineteens.

00:18:24: That is the Gazelka Mab, Mira Kizyumab, Rizan Kizymab because these are newer drugs but from what I do know of them they seem to be safe.

00:18:33: Okay!

00:18:33: But this a very early... We've only known Rizankis for one year in my hospital

00:18:39: I think for IBD, we've had it for a couple of years as obviously the trial coming through.

00:18:43: but its been used other conditions across other immune mediated disorders with no adverse safety signals to date.

00:18:50: Admittedly when other specialties use similar drugs sometimes drug dosing and obviously patient population is not identical.

00:18:57: so far good signal are seem reassuring.

00:19:00: The Jack inhibitors an interesting one because Across the IBD population, I don't know of any associations between Jack inhibitors and malignancy.

00:19:12: And i believe when there was a meta-analysis data across all of the immune mediated disorders use of jackinhibitors compared with placebo they're looking at all of different trials.

00:19:22: There wasn't significant safety signal.

00:19:25: The follow up period for all of those trials that went into that whether it's appropriate for detection.

00:19:32: but in general across the IBD cohort, there doesn't seem to be too much risk associated with Jack inhibitor use.

00:19:39: However, TOFA-CITINib one of three jack inhibitors that's licensed for IBD did in the rheumatology population and particularly older patients with rheumatoid arthritis show some quite also reasonably worrying safety signals when it came to malignancy.

00:19:59: To go into that a bit further, after real-world data showed an association between TOFA citizen abuse and all cancer development A randomized controlled trial of thousands of patients I think between three in four thousand with safety endpoints was conducted.

00:20:13: And across the follow up which i believe is about four years Inpatients with rheumatoid arthritis above I think, fifty-five years of age.

00:20:22: Patients who were managed with Tofocitinib had a hazards ratio of about one point five so an increased risk of developing cancer compared to those that were managed in anti-TNF instead.

00:20:34: So... In different populations there has been safety signal.

00:20:38: The EMA and the FDA have somewhat taken out our hands how to interpret this.

00:20:45: They've essentially said these drugs should be limited to when there's no other choices in patients with high risks, go coming back to our patients.

00:20:54: you've had a previous malignancy older patients.

00:20:57: These drugs are not suggested unless There is No Other Option.

00:21:00: However I still think especially considering the elderly needs To Be Balanced against The fact that everything Is more Risky In This Population including steroids and Including Collect Me.

00:21:12: so Really, there has to be some quite careful risk balancing.

00:21:16: But for me if I was thinking of using a Jack inhibitor in a patient with previous cancer or maybe even at the older patients.

00:21:24: it's something that i would discuss on an MDT setting and make sure discussions were underway with oncologists as well.

00:21:31: so it wasn't just one clinician taking on that risk with one patient.

00:21:34: It is properly discussed all alternatives considered.

00:21:40: So the take-home from that discussion, Hannah.

00:21:42: In terms of IBD drugs and risk of malignancy, thiopyrins increase risk combination treatment of thioprys and anti-TNF's increase.

00:21:51: Anti TNF mixed signals you said or?

00:21:55: Yeah probably some slight increased association with hematological malignacy and melanoma.

00:22:02: yeah okay.

00:22:03: And every other drug there is no link.

00:22:05: rather than jack inhibitors?

00:22:07: Well, yeah.

00:22:07: Junk inhibitor in other populations there is a signal associating them with increased cancer risk?

00:22:14: Yeah so that's much more reassuring than my knowledge ten years ago when I read the last set of guidelines!

00:22:19: So that...that's interesting.

00:22:21: okay Hannah just want to sort-of go through the practical aspects of counselling patients.

00:22:26: you know we recently and our team came across an individual who has active IBD, and Capricorn is high.

00:22:37: He has active disease, but he's so reluctant to start the medication because of the very risk of malignancy.

00:22:44: you present all that data to him.

00:22:46: You mention everything But this individual remains unconvinced.

00:22:50: How do you approach such patients in your practice?

00:22:53: So I think it was a really interesting point.

00:22:56: Firstly our job is not push patients to do things they don't want To make sure their right information for an informed decision that like theirself.

00:23:06: So you mentioned about talking about the risk of malignancy associated with different treatments and you've already counseled them, And he's already explained that You can offer them many drugs where to our knowledge there is no increased risk of Malignancy.

00:23:19: so I think That's really important.

00:23:21: i think asking The patient Where they got Their information from why They are so worried?

00:23:25: I Think it's Really Important because sometimes It Can come From social media or from Areas that are not necessarily peer reviewed.

00:23:33: for example, actually sometimes I've had quite good effect by explaining to the patients why i think it's safe maybe in the clinic letter signposting a couple of resources if they want to go read the information themselves.

00:23:47: The other side to counselling patients if they're not keen to accept treatment is make sure that their very aware.

00:23:56: And actually, when it comes to you've described a patient with colonic IBD-ostrial colitis.

00:24:01: This is an area where we're quite enriched with data that shows the active disease isn't itself quite as significant malignancy risk and there are even multivariate risk calculators available risks of dysplasia.

00:24:13: so by I think explaining to them... You can even show their patients with some of the risk calculates how significantly elevated their risk of malignacy.

00:24:26: wrong that I will add to that.

00:24:27: It sounds like you're describing a patient who has really tried not very many therapies,

00:24:32: but

00:24:34: in a patient whose tried a few therapies and they are not working the patient is raising the point.

00:24:40: yes there might be coming out of it.

00:24:42: i don't like the risks of my drugs ,you can explore whether their definitely taking the drug but presuming they are.

00:24:47: Collect me as no dirty word.

00:24:50: people have positive health outcomes without a colon when we've measured quality of life scores after surgical management.

00:24:58: So in the context of a patient really not wanting to explore medical therapy, surgical therapy is an option for them.

00:25:04: but again this has to be carefully counselled and careful discussion of risks.

00:25:13: Just let's move on to this more.

00:25:15: probably the most common clinical scenario that we deal with patients who have had past history of malignancy or patients doing the journey of their IBD treatment, develop a new malignacy.

00:25:27: I don't know how you want to deal with whether we can go class by class?

00:25:31: So i think you're asking me about evidence where like situation...I've just told you to use the evidence and now one there is minimal evidence and two, next to no-evidence.

00:25:42: So let's go with minimal evidence first.

00:25:43: so I'm being slightly flippant in the sense that i helped write a guideline on this...I do obviously think there are strengths for real world data but we'll talk through the challenges.

00:25:58: like has had a breast cancer, is living long-term on hormone therapy.

00:26:02: It's difficult to actually even be completely sure in your mind whether that's living with the cancer or if it's fully treated but not an active issue.

00:26:10: at the moment they're on there and have a flare of known inflammatory bowel disease.

00:26:16: thinking about how we approach patients Firstly, it's really just as important to treat that patient's IBD.

00:26:23: As it is to treat any other patients' IBD.

00:26:26: so we don't need... We shouldn't forget that and actually in I think it was Jordan Axelred did a review of real-world data And found the antiandrogen and antiestrogen or hormonal based therapies are indeed risk factor for flare for patients with known IBD who were managed for a breast or prostate cancer.

00:26:46: So in themselves, these patients can be quite high risk of disease flare.

00:26:50: so essentially when it comes to malignancy and IBD there are retrospective data sets in patients who've used our therapies after previous cancer And to sum that up sort-of.

00:27:02: in a nutshell none of them seem dangerous for all cancers as whole.

00:27:09: The challenge in interpreting these data is that if you're looking at a couple of hundred patients or some case series, twenty patients it's great to know that in those twenty patients everything has seemed to be safe.

00:27:22: This thinking about the newer drugs things like vedalizumab, oestekinumab and if you summarize them into a couple-of-hundred patient in a meta analysis there are systematic reviews brilliant but this probably isn't powered for really, really long-term follow up.

00:27:39: So I think it's really reassuring that there hasn't been any signals the medications are dangerous.

00:27:45: but if you want to look at the subtleties of specific cancer types and specific IBD phenotypes and specific drug That is quite a difficult thing To have really long term robust data on.

00:27:59: But that doesn't mean we do nothing, because obviously doing no harm means not using drugs.

00:28:04: It's just quite difficult to summarise what the exact safety profile is but so far most of our IBD therapies appear safe.

00:28:14: We've actually got more data, sort of I think for the anti-TNF like seventeen thousand patient years worth of summarized very small retrospective studies on patients with previous cancer.

00:28:26: There's a Danish population study looking at about four or five hundred patients with immune mediated disorders who used anti TNF after a known IBD diagnosis and there haven't been any adverse signals when it comes to new cancer previous cancer and so really positive take-home messages in all of our therapies including the anti-TNFs.

00:28:49: There are probably a couple scenarios where I would think twice about using the anti TNF's than people with a previous or recent cancer.

00:28:58: One of them I think would be hematological cancer, not least of all that the logistics.

00:29:03: if someone was about to be blasted with a lot of chemotherapy.

00:29:06: Another drug that works as an immunosuppressive therapy is maybe not-not the right drug for that patient and also because of the association with anti-TNF antipurins with haematological malignancy i'd think it's not their top choice.

00:29:21: Melanoma would be another one where I'd be slightly nervous in using an anti-TNF.

00:29:25: It was a patient with relatively recent melanoma diagnosis, this is partly because of Millilong's registry data that showed us slightly increased risk of melanoma per se with anti-tnf or be at a relatively small one.

00:29:39: it's partly also the in world immune checkpoint inhibitor colitis.

00:29:45: there are some very small number to suggest.

00:29:49: maybe patients who receive anti-TNF or infliximab rather than vedalizumab as their salvage therapy may have a slight increased risk of disease progression.

00:29:59: Now this is a subtle, small point that's not replicated in all cohorts.

00:30:03: so I'm certainly not saying never use it don't use it and severe immune checkpoint inhibitor colitis?

00:30:08: Not at all!

00:30:08: iIm just saying that in a more stable IBD patient when with the melanoma or history of recent melanoma When there are other options available We, Jack inhibitor drugs like the P-nineteen inhibitors.

00:30:26: The actual number of data is limited.

00:30:28: so far I don't know that anything to suggest they're dangerous but i think there are even small numbers in patients with prior cancers than then with any of the other drugs and EMA and FDA have this warning issued with regards to jack inhibitor use in high risk patient.

00:30:43: So jack inhibiter and someone with a prior or certainly an active malignancy would involve an MDT discussion, would involve discussion with the oncologist.

00:30:54: But that said I can think of at least one patient i know who's doing well on a Jack inhibitor With previous prostate cancer and this involved very careful counselling with the patients in very careful discussions but not an absolute no.

00:31:08: Yeah so what do you take home from that Panacea?

00:31:12: There is no one rule fits all.

00:31:14: talking about patients previous history of malignancy now treated, well let's call them they are in remission.

00:31:20: There is always that rest that there might have recurrence of this cancer.

00:31:23: so previously treated malignancies.

00:31:25: most drugs don't have any issues.

00:31:28: They can be used although you take a piece of caution.

00:31:33: and the scenario under white drugs which has been implicated or associated with malignances such as I do not know what typeureans anti-TNFs in case of hematological malignancies.

00:31:45: You kind approach that cautiously, especially when there are other alternatives available.

00:31:50: so you reach out for the other alternatives first.

00:31:52: Yeah and I also do think that, I mean IBD care is always a team sport but like when it comes to malignancy care.

00:31:58: you're talking earlier about the use of the MDT.

00:32:01: Yes the MDTs were getting busier and busier But they are still very important part of care And inviting our oncologists along to MDTs can be really useful When we discuss in these patients especially if more complex cases.

00:32:16: Okay, but let's say you or your patient is put in a position where they've had pre-disaster pregnancy now in remission.

00:32:23: And the only drug that works for them gives an amazing quality of life.

00:32:28: if he has an anti TNF you'll be perfectly happy to use these drugs.

00:32:35: Well, I think again it involves case-by-case discussion but iIthink there's not good evidence that in cancers as a whole and admittedly is talking about cancer.

00:32:46: there isn't, we don't have data to support that.

00:32:50: We shouldn't be using anti-TNFs as a whole in patients with malignancy.

00:32:53: when it comes to thiopurin and people with previous cancer the data was actually reasonably reassuring which is surprise.

00:33:00: well its not surprising but most recent systematic review has tens of thousands patient year follow up known signals that we know from the other patient population about the risk associated with thipurins and malignancy.

00:33:15: So I think we can take from that, but the absolute risk is low?

00:33:20: I've talked to before about using thipirins judiciously whether they need to be on both forever.

00:33:25: more a discussion where you have case by case without patients.

00:33:31: But i don't think it needs to be terrified of use these drugs in patients because previously had cancer.

00:33:38: Excellent.

00:33:38: That's well summarised, Hannah and I just now want to move on to patients who have active malignancy ongoing whether that is aggressive type cancers or slow growing cancer such as prostate cancer for example.

00:33:50: what should approach to medications?

00:33:53: IBD therapy?

00:33:54: yeah

00:33:54: really good question.

00:33:55: so i think it depends on what the therapy.

00:34:03: For example, if you've got someone who's with a new diagnosis of for example breast cancer.

00:34:10: Who was very stable on Vedalizumab for osteoculitis that wouldn't be scenario where I would want to stop the treatment because one has got the shock of a new breast cancer diagnosis.

00:34:26: The last thing they want is their colitis to flare, so I would keep them on treatment.

00:34:30: and again it depends also what oncologist then wants do.

00:34:34: because if you flip that scenario your patient was both on a thyroid period and an anti-TNF and the oncologists wanted give aggressive chemotherapy regime.

00:34:46: The current medication that they're on might not be the right one for them, and that would be a discussion to be made in an MDT setting.

00:34:54: If you were then going to step down IBD therapy—for example if someone is starting some aggressive atrop regime —they are already getting steroids or lots of chemotherapy—the anti-TNF does not need to be thrown into the mix by the neutropenic patient?

00:35:08: Then do we just stop the anti TNF watch weight monitor or do we start something else instead?

00:35:16: And I think, again that depends on patient by patient and what the cancer treatment is.

00:35:22: Coming to the UC scenario if you've had a patient who's recently had acute severe colitis has been really unwell is not only horrible for the patient, but if that happens again it's going to put a block in their cancer treatment.

00:35:36: If they're that unwelled and need to be admitted or emergency management for IBD then it might cause a pause on their cancer care.

00:35:49: so keeping them in remission is really important.

00:36:00: Will we watch and wait or will think about whether they go on, for example, Vedalizumab?

00:36:04: And again this is not evidence-based answers I'm giving you.

00:36:07: It's something that would be discussed in an MDT setting.

00:36:10: if the patient has had a tiny bit of proctitis and could potentially manage with topical therapy That might be the most appropriate treatment For that particular patients.

00:36:19: so i think You wanted clarity from me and i'm giving more questions.

00:36:23: No,

00:36:25: no.

00:36:25: That's fine because it doesn't seem to be as simple as I thought it would but looks like if patient needs the medication they are absolutely dependent on it.

00:36:36: all i wanted to know is that its not an absolute contraindication to use these drugs?

00:36:40: Thats a main thing everyone wants to know.

00:36:44: Is it an absolute... I cannot use anti-tenor for this patients who have active malignancy.

00:36:50: No, I think it's not.

00:36:51: There aren't really many absolutes.

00:36:53: just the caveat to that is for example if the patient had a melanoma and there's even some evidence that the anti-TNF may be driving the melanoma i'd want to change them to something else.

00:37:04: but I also think increasingly now The discussion is about...I mean we're mitigating a lot of risk amongst a lot Of uncertainty.

00:37:11: these are not going To be completely neat evidence based answers.

00:37:15: we do also need to at all times consider the risk of active disease and the risks of disease flare.

00:37:22: Okay that's good, thanks Mary!

00:37:25: The next one is a bit simple just in patients with active pregnancy.

00:37:28: are there any contraindications to use steroids?

00:37:32: No not that I know of.

00:37:34: if someone is flaring or needs steroids i think they need their steroids but the caveat for that is that steroids aren't always the best way IBD as you know.

00:37:46: So yes there are definite situations where people will need steroids, colonic disease that's having a nasty flare and we need to get that managed.

00:37:53: but now we're certainly not using steroids for maintenance.

00:37:55: if people aren't responding to steroids or have any need for recurrent courses As with any other patient We need think about If were reaching for the steroids.

00:38:04: do we need be reaching something else?

00:38:07: Hannah, moving on.

00:38:07: I think you meant briefly mentioned this before.

00:38:10: in terms of cancer treatment let's say chemotherapy other types of treatments Let us leave out the immunotherapy because that is a separate discussion altogether now chemo radiotherapy or hormone treatment?

00:38:22: does any of the treatment for cancer affect the IBD national history at all?

00:38:28: So

00:38:29: that's a really good question, but I'm going to also preface this by saying just because something may affect the IBD history doesn't mean we shouldn't use it and i think thats an important point for all drugs.

00:38:39: Im not gonna go into details of checkpoint inhibitors.

00:38:43: so in terms I mentioned looking at patients who have been in remission from their IBD, the hormone-based therapies are associated with an increased risk of disease flare.

00:39:01: When it comes to chemotherapy there is a known association although people often get gastrointestinal symptoms but I don't think they're associated per se.

00:39:15: When it comes to radiotherapy, this is really difficult but I'm gonna stress.

00:39:18: This does not mean that patients with prostate cancer who've got osteo-collitis should not have radiotherapy.

00:39:24: There should be a treatment option available these patients But whether someone Who gets radiation proctitis?

00:39:30: Is having a UC flare or as having radiation Proctitis sometimes quite difficult To distinguish and actually looking at the data for this different studies suggest Different things when it come to radio therapy in UC flair, but some of the studies suggest that there's no increased risk in hospitalization, and there is not an increase of risk for surgery.

00:39:53: Anyone with prostate cancer or radiotherapy has a risk to lower GI symptoms and radiation proctitis – our patients are less at risk than anything else.

00:40:03: but I don't think it's completely clear-cut to say this will cause the disease.

00:40:09: flare per se.

00:40:14: left side of the colitis is as well controlled, it can be when embarking on treatments.

00:40:19: But I don't think that necessarily causes a flare research.

00:40:23: Okay Hannah thanks for all the discussion.

00:40:25: so far we have covered few topics.

00:40:28: We've covered whether IBD is associated with malignancy.

00:40:31: then we cover drugs which increase risk of malignancies in IBD.

00:40:36: Now we covered how to use drugs if patients had previous history of malignancy and those who have active malignacy.

00:40:43: And I would ask listeners, they come across in these scenarios to refer the echo guidelines.

00:40:48: They're well written really succinctly very clear.

00:40:52: thanks for that!

00:40:53: Thank you.

00:40:53: there's also another Malignancy one under development at the moment.

00:40:57: my one will be coming obviously within about the next eighteen months but definitely keep an eye out.

00:41:03: And this is from Echo or this one BSG?

00:41:06: Yeah, there's a working group in progress.

00:41:08: I'm not involved in the second iteration of it although i know that people are doing and im sure its going to be an excellent very useful resource.

00:41:16: It will interesting see what areas are being focused on to renew literature review but yeah we'll work in progress.

00:41:28: Okay, anything that will not cover any other set of final thoughts or advice?

00:41:33: No I think that's good.

00:41:36: Yeah okay thanks for your time today and have a lovely day!

00:41:39: Thank you very much.