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Early modification of inflammatory burden in IBD patients by biologics

May 27 | 1:30 PM

Biologics have revolutionized the management of IBD. Past expectations were symptom control and improve quality of life. Therapeutic goals today are: Induce clinical remission, Maintain clinical remission, Improve quality of life along with avoidance of drug related and disease related complications. Decrease hospitalisation & overall costs. We will learn When we should use biologics? When would we consider early biologic therapy in IBD and selecting first line biologic therapy for IBD.

[Music] awareness of ulcerative colitism previously it was the disease of the west but now as you are aware the incidence of ibd very much [Music] [Music] of and was published 120 papers in international and national journals for 92 papers in national and international conferences indigenization of 2026 gastroenterology endoscopic accessories and also is a member of attitudinal board of digestive with this sir yeah good evening everyone actually uh as has been rightly said that may 19 we celebrate it as ibd day so with that actually it's a good topic to be included in this section uh we have with us two speakers uh uh who are actually renowned uh uh consultants in the field of luminy gastroenterologies and they specialize in treating patients of ibd we have dr harshad binay joshi from mumbai he is a consultant and ibt specialist in hn reliance hospital mumbai he has 20 national and international publications and he had echo aocc travel fellowship 2017 he learned small world ultrasound in ibd patients and he had i o ibd travel fellowship 2017 under mentorship of doctor gate hennis and learned various ibd specific management issues including clinical trial participation and he has been trained in canada for management of patients of ibd then we have the other speaker with us dr rinkesh bansul he is a senior consultant gastroenterology and hepatology biliary sciences at fortis memorial uh research institute uh gurgaon he is part of the principal investigator 11 global multicentric clinical trial projects most of them are on ibd he had 60 national and international publications and has been has nine awards to his credit for papers and oral presentation so by this you will learn that both the speakers are learned speakers in this specific subject then i like to introduce the subject as well that ibd is not uncommon uh in our country and it's a group of idiopathic chronic inflammatory intestinal condition so it's a it involves a small and large intestine globally it is estimated that more than 6.8 million people are living with ibd chronic uh crohn's disease and ulcerative colitis are the two major categories but there can be overlap and has it this both of them have distinct clinical and pathological features we can actually easily differentiate between crohn's disease and ulcerative colitis as ulcerative colitis actually is limited to colon only but if you go to cross disease it can affect any part of the gi tract but mostly it covers the small intestine that is the terminal ileum and the coal and it is it has been hypothesized that it is the result of defect in the innate immune system which allows bacteria to invade the mucosa of the gut and it leads to exaggerated adaptive immune responses and extensive bowel damage that is actually pathophysiology behind the ibd we can go to the next slide please as far as pathogenesis of ibd is concerned there is a genomic predisposition then exposures are also there in the lumen it leads to immuno dysfunction ultimately which leads to chronic inflammation in the gut and this strong inflammation either leads to actually depending on the type of the immune cells involved it can lead to ulcerative colitis or can lead to crohn's disease next slide as far as the course of ulcerative colitis is concerned there has been the study which has been over for more than 10 years and about 50 of the patients get remission after the initial activity one percent actually they land up with increase in the severity at the first go that is at the first presentation and five percent have a chronic chronic intermittent disease occurs in 33 of the patients so remission after the initial activity in 50 and chronic intermittent course in 33 we go to the next slide that's where the cross disease is concerned it's a progressive disease progression of the digestive damage and inflammatory activity in a patient of cross disease others like initially at the onset the diagnosis is there in the early part we diagnosed and ultimately the structure formation because of the trans-bureau environment and it can actually have a penetrating disease forming fistulas and abscesses ultimately they may require surgery and even after surgery they may develop structure again so it's a progressive disease with transparent environment and maybe after surgery also the the disease is relentless next slide as far as the cumulative cumulative risk of stretching and penetration in the patient of crohn's disease is concerned there was a paper including 306 patients and by the end of five years in the natural course 34 percent patients develop penetration or switching complication and by 20 years almost half of them get the complications so slowly as the disease the years progress the cross disease from the diagnosis the disease progresses and the complications come in during the course next slide as for the treatment goals are concerned in inflammatory bowel disease we have to relieve the symptoms of the patient that means pain abdomen bleeding per rectum and the complications we have to avoid steroids as far as possible because it leads to early remission of the exacerbation but it has got its own side effects to if they are continued long we have to prevent surgery in these patients and the ultimate goal is to have endoscopic healing and nowadays we are going to even histological healing in these patients we have to limit disability in these patients so as to improve the quality of life because it's a lifelong disease so by giving treatment actually it's not only actually we actually keep the disease under remission but also improve the quality of life next slide please so evolving therapeutic goals in ibd that means we should change the disease course there is there should be improvement in symptoms symptomatic remission should be there and it's not only symptomatic remission now we should have endoscopic remission and now we should go to the astrological remission and ultimately that is the potential ultimate goal is the histological remission it's not only improvement symptoms improvement inflammation there should be no inflammation and no disease when we give that treatment to these patients next slide now i i'll invite dr harshad to speak on how he'll manage and thanks takeda outside for giving me this opportunity so uh having learned from sir about what is the basic pathophysiology and what are the changes that has come through uh since the field of ibd has evolved so initially we had we were just talking about uh improvement in clinical symptoms but that has now changed uh 360 degrees and now we are talking about histology remission so we have come off our way long so it is very important that we just walk through once about the sequencing of this therapy so which therapy should be started how should it be started why is the necessity of sequences is what i am going to talk about next slide please [Music] yeah so why is sequencing really important in ibd as we all know there has been three aspects of remission that are spoken about initially it was clinical remission as we got newer molecules our knowledge about therapies improved we started talking about endoscopic remission and with the advent of biologic and newer biologic agents better sequence better dosing regimens the availability of trough levels antibodies against biologics we have really now been talking about clinical as well as endoscopic remission put together but we must understand that only 30 percent of patients in real life scenarios can achieve deep remission probably the reason for uh this low number is uh as we are i mean we have to sequence our therapies properly so that this 30 number can be increased to to the tune of our 50 to 60 percent next slide please okay we all know if we have to categorize the medication we can categorize that non-biologic therapies and biologic therapies i'm not going to go into too much of details the non-biologic therapies obviously would mean antibiotics then amino salicylic acids corticosteroid various formulations and immunomodulators mainly azat ibrahim or methotrexate next slide ah if you look at the therapies which are available for treatment of ibd uh i'm not going to again go into details of this all of us are aware about the five asses or immunosuppression what is more important here is corticosteroids are useful uh both oral topical or iv formulation in achieving a i mean in inducing a remission but they are not really useful in maintenance of remission as against that immunosuppressor and five aces are mainly used both for induction but mainly for maintenance of remission next slide please biologic therapies the foremost or the one which has the maximum experience so far is anti-tnf's infliximab and adeluma these are the ones which are available uh we are all aware about the effects the side effect how do they act uh mainly they act through the tnf mechanism and thereby they induce remission and are also helpful in maintenance of emission next slide please i think this is one of the most important slides uh wherein this talks about with the expanding therapeutic options how have we come forward from the earliest one of infiximab then adeline mark was marketed it was approved initially for crohn's disease and then subsequently for ulcerative colitis bedoli zuma was again also initially approved for ulcerative colitis uh the current one which are available in indian market is topher city name vedolizumab is available in addition to infliximab and adalimuma and there are many more molecules which are in the various stages of development and i'm sure in the next four to five years we would be seeing many of these small molecules which would be game changing as far as ibd is concerned next slide please we are all aware of the basic uh mechanisms by which these drugs act vandalism which acts on the alpha 4 beta 7 integrin or at the medicam pathway thereby blocking the trafficking of lymphocytes into the interstitial milieu which is responsible for inflammation ustekinumab is a il-1223 inhibitor which blocks the cytokines and thereby it prevents inflammatory cascade and the oral molecule with the only one which is available so far is stop acid in it which is an oral molecule against ulcerative colitis which is a jack inhibitor it targets the janus kinase pathway it's orally available it is effective in both induction and maintenance of ulcerative colitis it is not yet approved for crohn's disease uh either in india or western world next slide please so this is the pathway for radiology map action so as you can see in the upper portion are the t lymphocytes the t lymphocytes have this chemokine receptor alpha 4 beta 7 which binds to the mad cam 1 receptor or ligand which is there on the endothelial surface this activated t cell once it binds to the mad con is internalized across the endothelium into the inflammatory uh tissue or the gi tissue where it releases various chemokines and is responsible for maintaining the remission now uh the vadolysumac acts at the alpha 4 beta 7 area where it blocks the alpha 4 beta 7 so the uh lymphocyte is not able to attach to the myocam ligand which is present onto endothelium and therefore therefore it cannot get an access across the endothelium into the gi tissue and that's the mechanism of vadoralism causing blockade of the inflammatory cascade next slide please so we must understand here that it is uh the vidolizumab is a very specific or rather good specific biologic because it doesn't have the anti-tnf blockage which is seen with infliximab and biological i mean by the adalimuma because anti-tnf is available or is widespread in the body so the uh anti-tnfs are going to have a widespread action and side effects uh vis-a-vis vedo resume because it is very specific and targeted into the gut tissue it is a selective biologic therapy so the side effects especially tuberculosis which is quite common in our area this would be one of a better biology to go first now when we are choosing the first line therapy what are the thing that we need to look into or what are the characteristic of the drugs which we need to use so we must understand that once we start a patient on biology probably we are looking at a lifelong um probably we are looking at a lifelong or a long-term use of biology so we should uh be ready to get into i mean so we have to look into how it controls inflammation then it should also help in symptom control effectively it should not affect metabolic health of the patient it should preserve cardiovascular health because as we have seen high dose of antips have been responsible for certain cardiac side effects so we have to do that into perspective and most important it should have a good quality of life so because that is finally that is the goal of treatment it's not just going to be disease control but overall improvement in the quality of life so all these factors would have to be addressed when we are choosing the right medication in a particular patient next slide please so as a clinician these are few things that all of us are posed with i mean the patient is going to throw a lot of questions at us but when we are thinking rationally what we need we need to think uh when we are choosing a biologic first is the first line biology therapy is it hitting the right target of disease pathophysiology so if it is ulcerative colitis like sir said that it's a th2 response and crohn's disease so it has to target a particular area in the pathophysiology of the disease now the second most important question that we have to look for is is it achieving the safe safety profile or would it influence the patient acceptance because if the patient is going to experience more side effect obviously he or she is going to deny any uh i mean acceptance is going to be low so we have to look at the safety profile of the molecule when we are choosing the drug the third most important is the specific mechanism of action is it going to impact subsequent therapeutic intervention suppose you are starting with say anti-tnf if there is an anti-dna failure do we have a drug which is available uh which can be used in anti-task dns failure patients because if that is not the situation then we should not start as a particular molecule so we should always be ready with what are our starting points what are our exit strategies and uh in case of failure of the first line therapy do we have something to go by so all these questions need to be addressed before uh starting a first line biological next next slide this is the classical pyramid i'm not going to talk into detail so there are classically two approaches a step up approach and a top down approach uh step up approach is when the patient has a milder disease so you start with the medications which are milder which has lesser side effects and uh then as the patients based on the patient response or the disease phenotype you can escalate so if there is a failure of five say then you add on azo therapy or but if it is a high risk phenotype then you use the uh top down approach so that is why characterization of patient or risk phenotyping of patient is very important so what are the risk phenotypes or what are the high risk patients is something which we have to be very clear about so for example in ulcerative colitis if it is an extensive politics pam colitis severe ulcerations requiring iv corticosteroids these are the patients who are going to be high risk phenotype so in these patients we should aim to get their inflammatory burden under control quicker and thereby rather than going from 5s to immunomodulator we should straight away hit them hard with biologic and as the clinical remission is achieved or endoscopic remission is achieved then we can think of de-escalating the therapy for a maintenance review the high-risk phenotype for a crohn's disease patient would be young patients particularly males then those who have a visualizing type of disease those who have deep ulcerations those who have required surgical intervention at offset those are the ones which are and smokers so these are the patients wherein you should consider starting them on biologic first rather than meddling around with immunomodulators or fibrosis therapy so this kind of risk stratification is very important while choosing a good first line therapy next slide please so as we know biologics have really changed the paradigm of ibd it is useful in moderate to see the pronouns visualizing this is what i was talking about the high-risk phenotyping it's very effective in achieving clinical remission as well as altering the natural progress of disease thereby leads to deep remissions which is the ongoing target that we are talking about but you also must understand that there are certain risks which are associated so like i was talking about biologists have revolutionized therapy in terms of symptom control improvement in the quality of life it has bettered the goals that we are looking at so not just induction of remission but it has also improved maintenance of emission improving quality of life natural history is changed positively it has corrected malnutrition especially in pediatric population or adolescents by preventing malnutrition it has also reduced hospitalization overall cost which is again a very important aspect as far as our setup is concerned next like this so this is again one of the very important slides so what sir was talking about earlier the ulcerative colitis or crohn's disease will have this kind of relapsing and revision type of natural history and when we diagnose the disease and when the disease is in the early phase this is the window of opportunity because if we act here adequately then definitely we are going to prevent the complications or need for surgery because as we are aware about 80 percent of crohn's disease patients in their life's time need to undergo surgery and that is the case for around 40 to 50 percent of cases for ulcerative colitis so it is very important that if we act in this window our chance of preventing surgeries and preventing complication is going to be far better so we should always treat early to have a better control and overall outcomes next slide please uh all of us are aware about the contra indications to anti-dnf i'm not going to go much into details uh what is more important from an indian perspective is because anti-tnf agents are responsible for worsening of a latent tuberculosis so in indian scenario we have to be careful about later tuberculosis it is responsible when it therapy it increases various risk of skin as well as solid organ cancers a higher doses of anti-tnf is responsible for uncontrolled heart failure but this number is quite small and it is usually seen in patients where you use higher dose of anti-dna and obviously we have to be careful about when using it in patients who are more than 65 years of age again because of the risk of malignancies including lymphoma and infections next slide please this is again the same what we have to understand is what is the timing of using biologic so you have to have use the at right time you have to have the right dose and right time interval and the duration has to be also thought about when we are prescribing the biology so it should not be too early otherwise it is not going to be beneficial because if it is a milder disease we might be able to control with a non-costly medications and get it under control so it should not be too early neither it should be too late because then you have already uh missed the bus of preventing the complication uh we should use the right dose and interval so it has to be based on the international guidelines obviously we do have to make necessary changes because financial constraint is one of the important factors in our practice we can't have these standard dosing like followed in western countries so we have to do certain modifications but that has to be discussed with the patient in terms as to what we are doing why we are doing and what are what is it that we are going to look at by not giving the adequate uh dosing or giving lesser doses and seeing them frequently what are the pros and cons of this has to be discussed before starting the therapy and again regarding duration this is really important um as far as india is concerned we don't have to really worry about not too long because the patient themselves will not be willing to take medication for too long is basically that we should be looking at not too short so we we are starting the biologic uh with a view that we are we want to uh get a deep remission so until and unless we achieve deep remission not just clinical improvement but also mucosal healing that is i think the ideal time that we should start discussing about uh escape or the discontinuation therapy or exit strategies with the patient next slide please i think this is something we which i am going to skip through because this is we have already discussed what are the i mean it reduces hospitalization then uh multiple steroid usage etc so selecting first line biologic therapy like when we are selecting these are all the factors that i am sure all of us keep looking through inadvertently and subconsciously that what is the ibd phenotype severity and risk assessment then we always look at the comorbidity are there any overlap features extra intestinal manifestation one has to always be careful in terms of usage in pregnancy and in female of reproductive age group then we have to always be more careful especially in elderlies about combination therapies what is the effect i mean what is the evidence of efficacy that we are looking at what are the factors that we are going to look at as the improvement and overall outcome of the patient how is the patient going to pay is it is he going to pay through his pocket uh because that's in india unfortunately we don't have any uh financial support from the government and most of the insurance companies do not cover uh biologic therapy uh as a routine so we have to really discuss this with the patient uh about how is able to pay because that is once we start the medication we should not stop it abruptly because then the whole purpose is lost okay frequency then what is the patient preference does he have adequate set up where he can go and get the inclusions done or whether you should use a subcontinuous losing all these factors need to be discussed and thought about before selecting a drug and obviously safety is something which we anyways look at thank you next slide um i'm not going to go into details of this what we currently are looking at is basically uh two important drugs apart from anti-tnf one is which is uh approved in india for ulcerative colitis and veduo which is approved for ulcerative colitis as well as crohn's disease if you have to look into the specific the gist of this particular it's a very crowded slide but what you must understand is what is the earliest time to onset so how quickly are you going to expect any clinical response in a patient when you start them on a therapy so if you look at the anti-tnf uh the first onset of clinical effect is going to be within two to three days so once you give them the injection in two or three days is going to start going to start feeling better so this is something which we must talk to the patient because uh when you start them on any medication they are going to ask when should i when would i start feeling better so this is something which is very important that we need to talk to them uh uh is still not available but they also act pretty fast so overall if you look at most of the biologic act within three days to about a week's time so at least the effect starts immediately now uh the timing of maximum clinical effect might vary but uh a clinical response or a mucosal healing like uh dr bunsel is aware that he's part of many clinical trials 16 to 18 weeks is something which we always look at when we try to assess the mucosal healing that is because that's the time for maximum mucosal healing that we are going to look at so if you are going to uh do a repeat examination suppose you start the medic patient on a medication if you start i mean if you want to do repeat sigmoidoscopy you should not do it too early because then you might not see any discernible changes so this time frame has to be kind of kept in mind while monitoring uh while on biologic therapy there are various factors which are available the easiest would be biomarkers which are then we should also look at a complete documentation of biologic kingdom structure and frequency of infusion we should review them periodically so we should have a basic like an imaging or a repeat colonoscopy if not one year because then that will give us a confidence and we can also give the patient confidence that we are on the right track and there is adequate uh improvement in the medical part as well we have to think about the exit strategy as to when we are going to discontinue a particular biologic next slide please um i i think we i'm not going to go through details of this these are certain safety implications uh yes topher city this is one good slide because uh proposition is available in indian market nowadays we have started using it for our ulcerative colitis patients and the commonest side effect which is thought about is of uh herpes roaster uh if you look at the phase three tiles and overall phase two three trials uh what it was found that the risk of herpes zoster is not very high especially for 5 mp bdd dose which is the standard maintenance dose it is higher for ng bd dosing which is the induction dosing so in an elderly individual or immunosuppressed or diabetic patient this is something that we have to look for it is ideal that if we can give them vaccinations for herpes prior before starting them biology so this is an important factor that i wanted to stress upon next slide please um safety profile i think that is not something which i want to discuss here um it's fairly safe but there are certain side effects which i am sure all of us go through when we use the molecule uh positioning of low facility this is something important when do we use it should we use it for prior entities we can definitely use it for acute severe ulcerative colitis it can be used as an first line therapy or in failure of previous anti-tnf it can be used uh extra intestinal manifestation it can be used only thing that we have to be careful about next slide please i'm again skipping this slide next slide this is very clouded but i just want to emphasize one thing is that when you are using a combination therapy the risk of severe infections opportunistic infections both viral as well as bacterial infections are higher and it is more so for a combination therapy compared to monotherapy alone next slide please yeah so this is uh something which is good when we compare so anti-dnf had this basic problem of increased side effect because it is a pan acting molecule it blocks anti-dnf across various tissues that way pedolizumab is very uh specific so the u.s victory consortium which looked at one is to one propensity of score match analysis what they found that uh per se had lower rates of serious infections as well as lower rates of serious adverse events when compared with anti-dna as evident by the odds ratio of 0.37 and 0.29 so it is basically safer than anti-tnf obviously because it is more gut specific so the adverse events of anti-dnf are taken here to a great extent next slide please when you are looking at bio name back go back please go back you're going yeah yeah so when next yeah bus so when you are looking at bio new patient if you have to really sequence your biology uh obviously inflexi map comes first when achieving clinical emission probably this is because of it is there in the market for a long time there have been more studies and more data available as far as npc map is concerned interestingly beta comes the second i mean despite it has been in the market for a lesser duration of time compared to anti-dna it is it shows a very good control rate or induction of clinical remission in bioneer uc patient to facetime is the third one because goli is not readily available in india and adelium is one of the least as far as achieving clinical remission especially for bioneer patients next slide please next slide so when we are looking at patients who are moderately severe ulcerative colitis and if you have to really chisel down between anti-tnf and vedolizumab efficacy wise it is vedo is definitely more efficacious in ulcerative colitis compared to crohn's it has a durable response it is lower immunogenicity better safety profile because of gut specificity but it cannot be used in extra intestinal manifestations because the guts bigger again because the same factor of butt specific action uh cost wise i would say both vandalism and anti-tnf don't differ too much and dtnf has an efficacy equal in colitis and crohn's disease immunogenicity is one of the important problem apart from infections particularly tuberculosis and malignancies but the good fact is that it can be used as well next slide please uh this is again a comparison between uh the anti-dnf and vadolis map i i think what we have to look for specifically is uh i mean aluminum band bedo cannot be used in acute severe ulcerative colitis otherwise safety profile wise vedo is better over anti-dnf and efficacy wise we have more data for an antivirus particularly inflixima vedo stands second uh yeah i think that's my last slide uh again if you have to go through the pros and cons this is something which i have already spoken about various molecules are available we have to look at possible like what is the patient preference what is the side effect profile and what is the efficacy profile and i mean obviously we should use a molecule which has the least side effects and that is how we are going to use a first line biologic therapy and that will help you have a good clinical as holistic approach how up all about uh treating such patients with biologics yeah uh thank you and uh for providing a uh beautiful platform uh thanks dr nida for kind introduction and uh thank you very much for a nice talk uh by dr so regarding the my topic evolving therapeutic strategy in ibd uh dr uh beautifully covered the all the agents which can be used in ibd and which are available in india so next slide so our target is to achieve clinical as well as mucosal healing we our assessment for a clinical response by the by the parameters by the clinical response we can assess the mucosal healing by the endoscopical there are other uh bio markers like fecal cal protecting and crp which can be uh guided along with the provision of histological which can be a definitive for mucosal healing next next slide please so uh regarding efficacy uh by prior entity tnf therapy we have a lot of data regarding the biologics for previous as well as newer one there are certain uh things which a physician as well as the patients have there in mind about the biologics the regarding the physician uh the first thing is uh they are worried about the overtreatment they think that uh this is either too soon but sometimes it become late also they uh there are challenge uh to identify patients who will fall to respond these conventional treatment sometimes on treating according to disease activity the patient doesn't behave very well the second thing the physician generally are steroid addictive because they know that when they will start a steroid the patient will respond and they are easy to find easy to prescribe less costly and sometimes they use as a maintenance therapy also the third thing which uh physicians have their mind which is the fear of lack of efficacy or secondary loss of response to biological therapy which is still common they're concerned about the limiting future biological options some options are not available even nearby uh they also think if they use biological early then what are the other future options and these are the really practical issue the last thing there are complex management and safety concerns about the biological therapy sometime we need monitoring sometime we need to add different molecules and as a combo therapy we can use and sometimes there are complications associated with biologics like tb reactivations or malignancy regarding patient perspective next slide please the patients worry about the overtreatment everyone is now available on google every information they can when they start biologics there are lot of the first thing they find is tuberculosis reactivation and malignancy and they think that it is quite common so uh they think that biologics are too strong they are associated with lots of side effects so safety according to them is very much concerned regarding external addiction the patient is also addicted regarding steroid because it feels quickly better to the patient regarding the lack of efficacy or secondary loss of response to biological therapy they think that biological should be last resort because of lot of reason including safety and cost and also they think that if the the doctor is using biologically it means i am very severely ill which is not the case because this is the tectum we use next slide please so ah conventional treatment have their limitations five asi are not effective in cd but are they can be used in ulcerative colitis as a maintenance therapy in 30 percent of cases steroid again they don't have long term efficacy they have a higher risk of complication the steroids are not used in maintenance immunomodulator have lots of side effects like as a theoprints have pancreatitis hypersensitivity due to angel ft there are a lot of side effect associated with immunomodulator and sometimes uh the healthcare person failed to recognize the repeated cycles of steroid as a failure therapy sometimes we think that we have used steroids we have control the disease but as soon as the second time third time they used steroid and they found the benefits but this is not the actually beneficial for patient it means they are sort of corticosteroid dependent and uh they also not incorporate objective outcomes like endoscopic radios crop radiographic or astrological healing as a goal of therapy they all rely on the symptoms the symptomatic response clinical response is the only criteria which generally uh healthcare persons want to achieve next slightly so regarding the new molecules on the block uh this is the vitalism which is a iv molecules uh uh given in the infusion and uh generally as a monotherapy which recently available in india though uh data in indian patient yet to come but it seems as a promising molecules we need to assess the what are the treatment options we have we need to assess the patient's disease activity as well as the patient's uh disease cvrt next well so uh in ibd we need to uh assess the digi cvt we need to assess the what are the inflammatory burden by the crp by the fecal cal protecting by the endoscopic finding other uh intestinal portion of involvement and what the disease extent we need to see the impact on the patient what are the symptoms quality of life of the patient and we need to see all the complicated disease course also next slide please so sometimes the digi cvt component differ according to individual digits sometimes we see the patient are asymptomatic but on investigation they have a uh quite burden of disease and sometimes i isolated short alien structure can cause a lot of symptom including often few symptoms next slightly so we need to identify risk in cross disease we need to see the uh or the patient who are low risk like age if the clinical uh initial diagnosis more than 30 years when there is a limited anatomical involvement when there is no uh fistula no phys no structuring disease when there are ulcers are superficial there is no resection history but at the same time the we need to identify moderate or high risk patient which needs early biological therapy so at the opposite uh when the age at the initial diagnosis less than 30 years when there is extensive anatomical involvement of when there is a colonic involvement perional disease depulsation structuring disease penetrating behavior they all require early use of biologics next slightly so generally vitality map is not not be used obviously in seriously patient with alternative colitis in fistulizing crowns as uh dr said in crohn's disease induction therapy and in extra intestinal manifestations these are the uh relative contraindication of which we can say the vitalism can not be used rest other other diseases moderate to severe disease we can use in both ulcerative colitis and crohn's disease next slightly now the this is a very beautiful slide uh lots of data now available except in india but a lot of data available in world regarding vitality map there are short-term target intermediate target long-term targets short-term targets there are diversified study visible study germany two and other studies also they assess the clinical response as we train and they found to have quite significant benefit there are uh few studies which are available for intermediate target like crp at 14 or 26 week which was covered in versify study then fecal cal protecting also clinical remissions at week 6 and week 10 in germany 3 and endoscopic response at week 4 uh 14 inversify and radiological assessment we also have long-term data nowadays uh endoscopic outcome uh at week 52 by uh versify u.s factory constitutorium uh in endoscopic remissions we have now uh study also endoscopic remission at week 52 long term remissions uh in germany long term studies week 400 data also available uh which is recently published so and we have a radiological remission set with 52 universified so we have lots of data it short-term as a long-term target also regarding the weight loss next slide please so in 2016 eco guideline first time in uh included vetology map as a appropriate option in patient this chronic disease is refracted to steroid or nt tnf therapy at that time they have uh they have uh kept this as a reservier molecules in 2016. next slide please because at that time the data was not available but uh next few slides i will cover the importance study this is the gemini three trials uh in which where uh vidology map in uh induced clinical remissions was quite early with more pronounced effect in anti-tnf naive patient rather than the failure patient so they should not have a dictum that we can use this molecule only in antitna failure obviously if the patient is patient profile is good we should use a uh in entity tnf-9 patients also as this clinical issue this study shows clearly that at week 16 when we used in patient uh on nttnf now the the response rate was quite high rather than the entity enough seller and it was maintained at week 10 also next slide when we uh discuss that uh response to veterinary therapy observed as early as week two in ntt essential cd so this is a quite a good uh uh study in germany two and three when they they uh assessed and they documented the response as early as week two next slide please then the uh then the next study which versify uh uh showed that reduction in cdi score and crp fecal protecting was most rapid within four weeks and it was sustained at week 52 this slide so showing beautifully seed cdi is for crp concert and fecal cancer protection uh concentration it it was quite uh visible within four weeks drastically the uh the all the markers were saturn and it was maintained till the 52 weeks uh with the study uh sold next slide now the uh this is the love cd trial in which the proportion of patient achieving the key outcome at week 26 and 52 are documented and again they have uh documented beautifully that cdi remission cdi response endoscopic remission endoscopy response was quite significant in these patients next slide p so uh obviously we know if the digi duration is shorter they are associated with clinical remissions and mucosal healing rate are quite high which was documented in u.s victory consortium so we should use uh obviously uh in moderate to severe disease which uh have the perfect profile we should use early next slide the evolved study showed that biological night patients with non-complicated disease are more likely to achieve clinical response with beta genetic map so we know that if the digit is non-complicated any molecules like word only or any other molecules bef's very good so next uh again this is a victory trial in which they have assessed in early chronic disease and they documented that improved clinical outcome were achieved with early intervention with veto jelly map versus other entity tnf alpha in real world setting they have compared with the head to add in versus adalimu map not with inflexi mem and they found that the response were quite significant in comparison to adelium by the way next so in this study they have assessed the moderate disease activity who patient were nt tnf knife and uh they likely to achieve the clinical remissions and mucosal helium because aligning with the vital genome so uh in this study they uh they resp documented that it is quite significant uh benefit in comparison to uh next so regarding the safety profile of vader julium recently uh there is a study which was published in elementary uh therapeutic and pharmacology and there are around three thousand patient data ah week four hundred uh were even documented there is no increased incidence of adverse event or even after eight years of cumulative safety analysis there was no serious infection which lead to the uh in fact they have hardly documented two side effects one was the petrocellular carcinoma and one which was the just pml which were in documentaries in hiv patient the most infection were mild to mote in severity and they responded to treatment and patient the malignancy rate also seen uh almost the same there were no added malignancy the only one person had documented out of 3000 hepatocellular carcinoma and there obviously we know that low risk of immunogenicity was there and this was confirmed by the gemini long-term study which was published recently next slightly so regarding uh induction in cross disease as my previous speaker showed a slide in which the induction crohn's induction the role of vatology may was in question so this is the slide which there is a now data in induction also the patient who are bio experience and don't have adequate symptomatic response after induction the the best part is uh veteran has low immunogenicity and post work analysis from germany 2 doesn't show any benefit of continuing combination therapy so uh in uh in these patient corticosteroid patient dependent uh we can add uh these molecules and obviously we need a data for veteran web in crohn's induction next next so uh regarding uh clinical practice uh the treatment goal should be symptomatic improvements should be documented in six to ten weeks uh there may be early response and may be late response we should have crp and fecal a monthly or depending on the clinical response we should document endoscopic outcome when the we achieve the other target like clinical remissions and biomarkers and this would set appropriate patient expectations uh patients who have higher disease activity who have complicated disease who have experienced obviously we will take longer time or maybe they they maybe can't have the digits respond next so uh thank you very much uh and now i'll say i can open four questions we can uh thank you rinker for taking us through through the scientific data available for these newer molecules and now we have a few questions to both of you yeah so so like i said any risk stratification is very important when considering to start widow so a patient who has not accused severe ulcerative colitis but moderate to severe ulcerative colitis pancolitis then steroid failure non-respondent to 5sa or immunomodulator these are the patients that are considered best for treating patients with vitulisma as uh dr riches mentioned it can be used effectively as both a bio name in bio name patient as well as in patients who have failed prior nct who argue lost response to prior anti-dna it can be used and like i mentioned it is very good molecule in our settings especially because of its gut selectivity so in patients who have had a prior history of tuberculosis or those who had exposure to tuberculosis these are the patients who can be effectively treated with pedophilia as the first time therapy uh the last slide with dr english mentioned it showed that the response was fairly good in patients who were treated early so less than two years duration when it was compared head-to-head with anti-tmfs so i think uh when these kind of moderate to severe patients we can use that as an upfront molecule rather than waiting for anti-tnf failure and so it can be used as a first line therapy and what about uh uh this is i think the data although it is claimed i would still be a little hesitant in using it upfront because uh infliximab obviously has a good data uh both and i mean inflexible um also to an extent i would consider that as a second line therapy after failed and dna and doctors actually your specific guideline because all these studies are from the best and yes guidelines american guidelines so do we have to have not sir a very good question sir and in fact you are here i will urge you to uh develop data regarding pedo julie map and we should include uh this uh molecules in indian guideline because uh now it's available in india so i think we uh our ibd patients uh are different from the western country and i think we should this would have or on guideline for uh treating ipd patient in india yeah you're very right we should actually the the profile of patients are very very different from what we see in the best actually and as far as this uh switching is concerned switch from one to the other one when you decide actually it's from switch from one biology to the other yeah please so uh sir i i mean my first thing is when we are going to decide a molecule i think that's the time that we have to be more careful because like i said when you are starting the first molecule think as if you are going to be using that as for lifetime so the first molecule has to incorporate everything it has to have a very good safety profile financially it should be good for the patient it should achieve it should have a good data as far as the deep remission is concerned obviously it should have lesser side effects so a molecule i am sure that this is there is no gold standard available but whichever is the best suitable taking all these things into consideration has to be chosen first because unfortunately in india like if we fail say anti-tmf then again pushing the patient to use a new biologic agent is going to be really difficult both in terms of convincing them the cost implications and using medication because they are going to ask 100 so i think the first molecule has to be really precise uh fortunately uh when they compared both anti-tnf mainly adeline lab and bedolin there was a good data to back up on like if there is an anti-dna failure resume is a good choice and it also is shown to be quite good as far as the first line therapy also uh i think one of the good thing which meadow has come up now is with that patient support program i think that's something which would be useful because patients those who are less affordable can get a good benefit out of that like they can get staggered payment and all that so i think uh our setup apart from the efficacy and side effect third most thing is going to be the cost so we have to i mean that will be my first choice in this i mean these three factors would be my choice of determination before choosing the product and doctor in case is there a role of actually combining these biologics with immune modulators actually combo therapy yes sir uh there are uh controversy regarding the adding amino suppressant along with this i think regarding i'm not aware that vadoli i think have the only mono options no combination i have not encountered any studies which have the combo therapy but in anti-tnf yes the role of immunosuppressant is there and in my opinion we should use along with npta but regarding and how long to be used actually you know somebody who has responded to say it's a lifelong disease yes i think what i mean obviously sir sir would have the best experience as far as the molecule use is concerned but uh i think sir i would feel that at least a good one year or two years of deep remission if we can achieve then we can think of exit strategies because in that time the inflammatory burden would have come down and maybe we can just use other thioprin or 5sa as maintenance therapies to facilitate has come up in a way that we can use in ulcerative colitis so maybe like a switch on switch off kind of therapies so but i think sir would have the best experience to tell us about this particular question yeah i think so actually you have to see the natural course of these patients when they are on biologics i mean ultimately the goal is to get the mucosal healing so if the healing if it is achieved i mean there is a possibility of actually stopping the tree [Music] i think we are exceeding the time so is the time to close the session we have had very good talks by dr herschel and dr richards they have taken us through the journey of treating moderately severe crohn's disease and ulcerative colitis so thank you to both of you [Music] um [Music] such [Music] thank you to everyone on behalf of netflix as well thank you so much for joining us for this session and thank you to dr nandan as well from technida and thank you to our audience thank you thank you thank you very much

BEING ATTENDED BY

Dr. Vasavi Paluri & 871 others

SPEAKERS

dr. Rinkesh Bansal

Dr. Rinkesh Bansal

Senior Consultant, Department of Gastroenterology and Hepato-biliary Sciences | Fortis Memorial Research Institute, Gurugram

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dr. Harshad Joshi

Dr. Harshad Joshi

Consultant Gastroenterologist & IBD Specialist, Department of Gastroenterology and Hepato-biliary Sciences | Sir H.N. Reliance Hospital, Mumbai

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dr. Sandeep Nijhawan

Dr. Sandeep Nijhawan

Head of Department, Department of Gastroenterology | S.M.S. Medical College, Jaipur

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dr. Rinkesh Bansal

Dr. Rinkesh Bansal

Senior Consultant, Department of Gastroentero...

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dr. Harshad Joshi

Dr. Harshad Joshi

Consultant Gastroenterologist & IBD Specialis...

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dr. Sandeep Nijhawan

Dr. Sandeep Nijhawan

Head of Department, Department of Gastroente...

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