Indian evidence of r-ATG As immunosuppressive agent in renal transplantation
The RICE study, which assessed the safety and effectiveness of rabbit ATG in Indian patients undergoing renal transplantation. Conducted on 325 patients from 20 centers between July 2017 and February 2022, the study showed promising results. The primary endpoint was acute rejection at 12 months, with only 6.7% rejection at 6 months and 7.7% at 12 months. Renal function was stable, with serum creatinine and eGFR showing minimal changes over the year. The study concluded rabbit ATG is safe and effective, with low rejection rates and good recovery of renal function.
Additional studies compared rabbit ATG with other induction agents like Basiliximab, showing rabbit ATG's superior outcomes in reducing acute rejection and infection rates. Overall, these findings suggest rabbit ATG is a reliable induction therapy in both high and low-risk renal transplantations, improving patient outcomes and reducing rejection rates. In this episode, we will discuss the Indian evidence on rabbit ATG (Anti-Thymocyte Globulin) as an immunosuppressive agent in renal transplantation.
Dr Manish Malik Video
Good evening, I am Dr. Manish Malik, Vice Chairman of the Frolji, Sargadara Mospin, New Delhi and thank you so much for joining me and thank you, Team Thaybo for having me on this academic session today evening. So I will now start my slideshow. So the topic of today's evening session is Indian evidence of rabbit ATG as immuno-separative agent in the raspberries. We have all been using rabbit ATG or hypoglobinate as we know it more fluidity for a long time now in the rindar transplantation and all the frolologists are well versed with its ways. So some disclaimers will discuss it as benefit physicians to discuss updates on Indian evidence of rabbit ATG as immuno-separative agent in the raspberries and its benefit education purpose only. It is possible that some information on specific drugs is out of a room label usage and physicians are requested to refer to the full prescribing information before prescribing any product basis of today's talk is what we call the rice study or the rice industry. So the anti-thimacyte lobulin in renal transplantation, the rice study. This is an Indian study. The aim of the study was to assess the effectiveness as safety of rabbit ATG used as an immuno-separative agent in Indian patients under the rindar transplantation. This was a national prospective observational poor study conducted on 325 patients from 20 nephrology central in India between July of 2017 to February 2022. The patient profile was all patients aged among 80 years under the rindar transplantation. The intervention was rabbit ATG at least one dose combined with anti-infection prophylaxis in terms of steroids, anti-metabolites and cnine. So you have a reduction of rabbit ATG, you have the triple drug immuno-separation of CNI, anti-metabolite and steroid and then you have the anti-infection prophylaxis as per standard guidelines. The follow visits at 14 days plus minus 3 days and 3 months, 6 months, 9 months and 12 months post transplant plus minus 7 days. The primary endpoint was acute rejection at 12 months and other endpoints was rejection free graft survival, infections and real function. The mean cumulative dose of the induction dose was 2.6 milligrams per kg body weight for the patients. What was the outcome of treatment for the right study? The treatment failure at the end of 12 months was negligible. Only 21 patients, which is less than 10% in the valuable patient population showed biopsy proven acute rejection. So if you want to see the rates of acute rejection over the 12 month period and at follow up 6 months, the risk of acute rejection was 6.7% and at 12 months, the rate of acute rejection was 7.7% and if you were to assess the types of associated acute rejection, then the cellular rejection was seen in 77.3% and the body middle rejection in 9.1% and mixed pathology was seen in 13.6%. So what were the findings from the right study? The what was the causes of freedom failure, diabetes mellitus surprisingly was only 8.4%. The hypertension was 61% CKD 19.4 and ESRD 7.4. If you were to assess the renal function post transplantation, so this was assessed either using serum creatinine or EGFR or rejection free survival. So these results were assessed and plotted as the bar diagram visible on your screen where the dark blue bar is the 6 month data and the light blue bar is the 12 month of the one year data. At 6 months, the serum creatinine was 114.01 micromole per liter and at 12 months, it was 1.2.89 micromole per liter. The EGFR was 64.59 mps per minute per 1.73 m2 at 6 months and 64.93 at 1 year. The rejection free graph survival was 93.3% at 6 months and 92.3% at 1 year. Also the authors concluded that rabbit ATG is found to be safe and effective in the Indian population and all of us have been using rabbit ATG for a number of years now I would say decades and most of us agree with this kind of results where rejection rates have come down to less than 10% and the recovery of the real function is fairly good. What is the role of rabbit ATG in haplotype batch related low risk living donor kidney transplantation? This is the kind of patient which we see very frequently in our daily practice. Most of us practice related live roller kidney transplantation and haplobatch is a major chunk of those live related donors. This is again an Indian study from PK Jars group published in India's relationship. So this is the three groups we anyways which all of us follow. So the study included living related kidney transplant more than 80 years of age and a total of 350 patients were there. They were trying to three groups. One group had no induction, 143 patients. The second group had basically similar by the induction 112 patients. And the third group had rabbit ATG and induction, 95 patients. The study duration was February 2010 to 2021 with at least six months of follow up. The intervention all these patients were initiated with ticker all of us 0.1 milligram per kg divided two doses along with microfibilate, mofatil or sodium. Microfibilate, mofatil, 1 gram twice a day. And if the sodium swan was used then it was 720 milligrams twice a day. Oral prednisolone 40 milligrams daily from post of day one. A per to 20 milligram of the day of discharge. 100 milligram of IV hydropartisone every 8 hours and induction either with rabbit ATG and 95 patients and the dose was 3 milligrams per kg or basic Lixibab 20 milligram dose in 112 patients. Then just to remind you the biggest group was the group without induction 143 patients. What was the immunosubmission protocol implemented in the study that rabbit ATG was induction was used so 1.5 gram milligram per kg body weight each day on the day of transplantation and post of day two. Whereas if the patient was given basic Lixibab then 20 milligrams of the day of transplantation and another 20 milligrams of post of day four. With high prednisolone induction 500 milligrams IV interoperatively and hydropartisone 100 milligrams IV every 8 hours of the day of transplantation take an all-in bus starting those 0.1 milligram per kg body weight into two divided doses and the dose of MMA5 maturity and oral prednisolone 40 milligrams per day from post of day one. A per to 20 milligram per day of the day of discharge and coming down to 5 milligrams per day at the end of third month and of course tri-methylparems, sulfur-methamcilinine prokaryxis for 6 months and CMV profile axis with valgensyclobate for 3 months for ATG induction patient group or 6 months is CMV status for the plus and R minor. Again this is kind of standard we all use. What was the outcome with rabbit ATG versus basic Lixibab versus no induction? So the patients were a stage of 3 parameters the first was VPAR, biopsy-Coven acute rejection the second was infections, auto-parameters and third was CMV infections. In the no induction group which was green versus the rabbit ATG blue versus basic Lixibab gray or purple whatever is even a screen. So the left hand side bars on the VPAR and as you see the rabbit ATG the risk of rejection was 5.3% this was similar to the previous rice study which I mentioned which had 6 and 7%. If you compare that with no induction it is 17.5% and 18.8% in basic Lixibab group. So definitely in the low risk patients also basically CMV have no advantage over no induction for infection, outcome parameter. Surprisingly the rabbit ATG has the least number of infections 42.1% 43.4 for no induction group and 47% in the group which received basic Lixibab. CMV infections again 6.3% in the rabbit ATG group but then these patients were the one who also received well-gunned segment of Lixib. The CMV infections were higher at 10.5 in the low induction group and 12.5% in the basic Lixibab group but normally because these patients did not receive CMV profile access. So patients induced with rabbit ATG have significantly lower VPAR that is biopsy-proven equidjection and fewer CMV infections. So the authors summarized that rabbit ATG is well tolerated in haplo batch related lower risk living donor kidney transplantation. Then the other study was published in transplantation by Dr. Koote and others. So this was the largest study. The rabbit anti-thymocine-orbulae renal transplantation evidence of the largest multistutted study in India. So this was a retrospective cohort study was conducted on data from ambient compatible 1,759 transplants and abial compatible 33,157 transplants. All of these were live donor kidney transplant who assessed and comprehend the desensitization protocols, complications and outcomes of abial compatible live donor kidney transplantation. So what was the study design? This was a multi-center retrospective cohort study of data from India between 2nd March 2011 to 2nd July 2022. The study population for abial compatible was 1,759 patients all live donor and for abial compatible abial compatible was 33,157 again live donor kidney transplant. What was the intervention for abial incompatible desensitization protocol plus itoxy bap plus rabbit ATG induction plus the triple immerous separation everywhere, prednisoload and ticarolypus? The out of the abial compatible group that we have, the rabbit ATG was 775 patients, the ATG Crescenius was 152 patients and IR2R blocker or bacylic C-ray was 632 patients. At the end point, primary end point was abial compatible management protocols, hard end points and risk factors. The hard end points included biopsy mode equipment rejection, graph loss and mortality and the secondary end points for infection and post transplant application. So when you were to compare the abial compatible transplant with abial compatible transplant, this was done over a median following over 33,6.3 months and these patients were compared with respect to mortality, graph loss, biopsy mode equipment rejection, overall infections, non-violent infections, CMB infection and BK virus infection. So if you were to compare these, this was done as the bar diagram showed where the new bar is the abial compatible and the gray or the purple bar is abial compatible line of the transplant and if you see the mortality was 9.49 in abial compatible and 9.23% in abial compatible which means similar mortality, the graph loss was lesser at 7.73% in abial compatible compared to 8.12% in abial compatible but no statistically significant difference. The biopsy fluid review rejection was slightly higher in abial compatible at 12.96% as compared to 12.13 in abial compatible but again no statistically significant difference. Overall infections were higher in abial compatible at 18.72% as compared to abial compatible 17.39% again no difference. The non-violent infection was similar 11.3% in abial incompatible and 11.7% in abial compatible. CMB infections lower again in abial compatible 3.75% as compared to 4.5% in abial compatible and BK virus again lesser risk in abial compatible which is 1.13% as compared to abial compatible 1.5%. So abial compatible versus abial compatible showed no statistically significant difference and as per this study abial compatible live lower period transplant is safe and feasible with the right choice and dosage of induction therapy. So that is very very important. So the author summarized that abial compatible live donor kidney transplant is safe and feasible when induction therapy aligns with the patient profile. Now coming to another publication by the PKGURB in individual the Frolgi 2021. This was titled rabbit anti-thipocyan globulin versus anti-thipocyan globulin for serious safety and efficacy. So this was the comparison of one brand which we do as thymeoglobulin and the other brand which we do as graph log. So again this was a single center introspective study to compare the outcomes of two types of anti-thipocyan globulin for induction therapy namely what rabbit ATG and the other was ATG Tricidius. So adult patients are no renal transplantation between January 2017 and October 2019 by included. The median follow of was 32 months. The induction regimen was either 3 milligram per kg body weight this was 255 patients compared to ATG Tricidius 6 milligram per kg 78 patients. The material stimulus separation was triple immunosuppression steroid MmF and CNI in the form of technolibus. So this was the results which can be seen in the bar diagram on the right hand side where the green is the ATG Tricidius and the blue is the rabbit ATG. So what was the outcome compared at 22 months one was patient survival which was similar 99% in rabbit ATG at 98.8% in rabbit ATG and 99.8% in 18 year procedure. That salutured guard survival again at 22 months was similar almost with ATG Tricidius 99% and rabbit ATG 100% but BPA or biopsy malachive rejection was much higher at 12.8% in ATG Tricidius and only 5.1% in rabbit ATG with a p value of 0.04 so statistically significant. So the short term patient and death sensor graph survival graph function and infection rates were comparable except for the rate of BPA. So rabbit ATG shows a notably lower BPA or compared to ATG Tricidius a form of safety and effectiveness as the induction agent. So in all the studies which we have seen till now we find that with rapid ATG the rate of biopsy control acute rejection is around 5 to 7%. So with this we come to the end of this slide show but there are a few more points that I would want to make before I say good night to all of you and that is I would like to take your attention to what we call the Barai registry RISC which is the rabbit anti-thymoside globular RITG as induction immunosuppression therapy in patients undergoing renal transplantation. So this was population in general of transplantation and this was a registry multi-center registry from all over the country. So this was a multi-center trial of 22 centers and this had a enrollment of B25 patients. So I would request that all of you could probably go back to this registry and see how and what is the impact of rabbit ATG. I would want to take your attention to certain important points. The cumulative induction B dose was approximately 2.6 milligram per kg body weight with a standard deviation of 1.5 given over two doses. The B GFR was 64.59 at 6 months and 64.9 at 1 year. The incidence of rejection was 7.7% at 1 year and at 6 months was 6.7% and at 1 year was 5.4%. In total three 42 adverse events were seen and Pirexia was the most common. Only seven patients were reported to have died during the study. So this was one study which revealed the effectiveness and safety of rabbit ATG induction therapy in the Indian context and these data were similar to the international data which we have which have enrolled much higher numbers of patients. So if I were to give you some take-home points the first is that rabbit ATG or fibroblibilis is an effective induction therapy with the rejection rates of less than 5 to 7% depending on which trial you are talking of. Now the dose optimization is very very important and I would say that a dose between 2 to 3 milligrams per kg per kg body weight and given in two doses is fairly okay. The risk of infections as per these various studies including CMV, BK polyammar virus and other infections in general was similar to not using induction therapy at all one and as compared with simulate and as per the huge data which was published by Gautam Cote's group I have shown you that immunocompatible versus immunocompatible if you use a right induction therapy then your outcomes are similar and finally one other thing which is quite enlightening is that even in low risk transplant the risk of reactions are fairly high almost to the tier of 20% if you do not use induction therapy or you use basic LEXI BAP and with with rabbit ATG the risk of reaction comes down to 5% even the low-income patient outcomes may be safe so one can not recommend but suggest using rabbit ATG may be in a lower dose even in patients in a half-low-matt live related donor transplantation to reduce the risk of biopsy-probinecure rejection and to reduce the risk of high dose steroids being used as anti-rejection salivary therapy which was secondarily increase the risk of infections which which was probably the message given by the authors we would be open to answering any queries which you may have after seeing this presentation so my email id or a communication address would be given to you in which you can always forward your queries and we would be more than happy to answer all these queries I think with that we can come to an end to this presentation and thank you for a patient hearing and it was a pleasure doing this presentation thank you so much
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