BSPGHAN 2021 Virtual Annual Meeting

27- 29 April 2021

A SINGLE-CENTRE PROSPECTIVE OBSERVATIONAL STUDY COMPARING PROACTIVE WITH REACTIVE THERAPEUTIC DRUG MONITORING (TDM) IN TWO COHORTS OF CHILDREN WITH INFLAMMATORY BOWEL DISEASE (IBD)

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Anna Pigott
Anna Pigott
2 months ago

Interesting and very relevant to practice. How long did you include the follow-up in the reactive testing group? you followed up only for 9 months in the proactive group, was the timescale comparable? Were you using the same drugs or biosimilars in the different groups? We notied we seem to e getting more antibodies in our patients on biosimilars comapred with Remicade. (Maybe this is because we were in PANTS at that time and had more access to levels?? not related to change in biosimilar ) Results are a little tricky to see in the table, but appreciate you are trying to squeeze a lot in a small space!

Marco Gasparetto
Marco Gasparetto
2 months ago
Reply to  Anna Pigott

Thanks a lot Anna for reading the poster … I am sorry for the Table, it looked a bit bigger on the original file … Your point is really important: I do have different follow-up durations for the proactive cohort (9 months available at the time I submitted the abstract – 1 year available at present) and the historical cohort (follow-up range between 1 year and 3 years) … The aim is to extend the study to a longer follow-up for the proactive cohort so I can get final / more complete data. This data remains preliminary. Nevertheless, the data on the Table comparing proactive and reactive groups refers to the same follow-up durations, i.e. I only recorded “events” up to 9 months of follow-up in the reactive TDM cohort.
Your point about infliximab originator vs biosimilar is also very relevant. Most of the patients in the reactive cohort received IFX originator whereas all patients in the proactive group were treated with a biosimilar. Nevertheless, we still see significantly lower occurrence and lower level of anti-IFX antibody in the proactive group, that suggests us proactive management remains advantageous in this respect.
Thanks so much for your comments + discussion!
Such an interesting topic that needs more data / evidence.

David Campbell
David Campbell
2 months ago

Thank you Marco, this is an important area of common sense IBD management. Can you think about some summary points on proactive TDM that you would like to share?
Next, the link between neutralising HACA and allergic reaction may well be HLA linked. There is a study group in Liverpool looking at this association. This is something to keep a watchful eye upon as it may shed light on some new important mechanism of drug reaction and LoR.

Marco Gasparetto
Marco Gasparetto
2 months ago
Reply to  David Campbell

Thanks David!
In our Department, we shifted from using reactive TDM to proactive TDM in 2019, that is when I joined the team at the Royal London. So far, we have seen that by using proactive TDM patients stay much longer on IFX, i.e. there has been a drop in treatment discontinuation due to loss of response, thanks to optimisation of IFX dose and intervals between administrations based on drug level/antibody. This postpones switching to different classes of bliologics and helps managing patients in the medium/longer term before running out of options.
In view of the above, I set up a quality improvement project to document objectively what the advantages are of using proactive TDM. I hope that I can develop this further onto an observational study by expanding the prospective cohort managed with proactive TDM and by monitoring patients during a follow-up of at least 2 years. This is the current plan. It would be great to look at this in the context of a multi-centre / national project. Literature gives only partial/initial evidence on the benefits of proactive TDM and recent guidelines (ECCO/ESPGHAN) have provided contrasting messages due to the lack of data.
I didn’t know about the study on anti drug antibodies and allergic reactions at Liverpool … It would be great to collaborate with them in case they were keen on expanding their cohort.
I attach here our internal protocol for proactive TDM … We are generally happy with an IFX trough level of 3-5 ug/ml although according to the PANTS study and some other recent evidence we should probably aim for 7 ug/ml (and 12 ug/ml for Adalimumab).
My summary of the potential benefits from using proactive TDM:

  • Reduces discontinuation due to loss of response
  • Postpones the need for switching to different classes of biologics i.e. treatment options remain available for longer
  • Potentially reduces risk of allergic reactions
  • Optimisation improves cost-effectiveness / reduces expenses for NHS

Many thanks David for your helpful comments.

Gasparetto_M_BSPGHAN_Flow_Chart_image.jpg
David Campbell
David Campbell
2 months ago

This is very helpful. Also very important.
It would be so useful to do an economic evaluation of this service?
The costs of becoming unwell (on a family, rather than a single individual), plus the costs of further investigations such as repeat endoscopy when class switching occurs, plus the cost of drugs at much higher rates than IFX or ada will be very interesting.
The data you collect now may be analysable by a health economist who will let you know what further data is needed. Can you compare with historical controls or collaborate with another site where they are not able to do proactive TDM?
We would all benefit from that analysis

Marco Gasparetto
Marco Gasparetto
2 months ago
Reply to  David Campbell

I couldn’t agree more. Thanks a lot David, these are great suggestions. Once I have completed at least 1.5 year follow-up + expanded the cohort to around 40 patients managed with proactive TDM, I will certainly try to liaise with other centres that might be interested in addressing this question + a health economy analysis sounds like the complementary data we need to make this fruitful. Many thanks indeed … I will ask you separately which protocol is used in Sheffield and if you/your colleagues would be keen to join us so we can expand this to a multi-centre project.

Farah Barakat
Farah Barakat
2 months ago

Thank you Marco for sharing the RLH data- excellent work and I totally believe in the proactive approach. I also echo your voice regarding the importance of the context of a multi-centre / national project.

Marco Gasparetto
Marco Gasparetto
2 months ago
Reply to  Farah Barakat

Thank you Farah! Happy to read you enjoyed the poster … This is a topic I find really interesting as practice has changed so much over the past few years, evidence is still limited and the use of TDM is so different in different Units. Fully agree … It would be great to make this a multi-centre project.

Anthony Wiskin
Anthony Wiskin
2 months ago

These are interesting data Marco. Anything on overcoming high level of IFX by administering more drug – decreased interval/increased dose, and maintaining response to IFX? Do you routinely stick to a standard schedule and amend following TDM or are there some patients that you go straight for 10mg/kg or 4 weekly schedule?

Marco Gasparetto
Marco Gasparetto
2 months ago
Reply to  Anthony Wiskin

Thanks a lot Anthony! We have regular “virtual biologic ward rounds” where we combine information from proactive TDM with the patient’s clinical progress and their systemic/faecal inflammatory markers. If we are worried about the patient’s response and we find a very low IFX level, we will most likely go to 10 mg/Kg 6 weekly straight away, i.e. skipping one step from the flow chart attached above … We generally never escalate directly to 10 mg/Kg 4 weekly though … We try 6 weekly first. Hope this helps a bit, many thanks again for reading the poster and for your comments.