I was out in the garden when my phone rang. It was one of the IBD nurses at Guy’s Hospital.
“Can we agree a date for your first infusion?” What infusion?
“The vedolizumab” What vedolizumab?
“Your consultant has the go-ahead for it” That’s news to me!
She agreed to hold off booking it for the time being as I wanted to discuss it with my consultant before we went any further. She would, however, put the necessary blood test and chest x-ray requests onto the system as they were both pre-requisites of starting vedolizumab. I emailed my consultant to ask if he could arrange an appointment for us to talk through this new drug. I was aware that a growing number of “MABs” were being used in the treatment of IBD. I had seen patients discussing their pros and cons on social media but hadn’t taken a great deal of notice as they were not part of my treatment.
Wednesday 13th March 2019 – Guy’s Hospital – The Bleeding Clinic
I used the appointment at the Haemophilia Clinicas a chance to revisit my haemoglobin level which had been consistently low for quite a while despite taking iron tablets for so long. Would an iron infusion be more effective? The haematologist looked at my last blood test results and agreed that the Hb reading was low. So were my white blood cells. Another bone marrow biopsy would be worthwhile to check for any changes since 2013.
I mentioned the proposal to start vedolizumab for treating the Crohn’s inflammation. Would my other conditions need be considered? He consulted the online medication “bible” and said that vedo, being gut specific, should not cause interactions.
He would book another appointment with the general Haematology clinic but in the meantime would get me to provide blood and urine samples. I explained that the IBD Infusion Unit had already requested specific blood tests. Would it be possible to get these done at the same time? “Yes it would”. I went off to see the phlebotomist who removed nine full phials of blood. My previous record was eight. Whilst this may sound a lot, when you consider that each phial contains only 4 or 5 ml of blood you realise how little it actually amounts to. Certainly nowhere near an armful
…then off to visit the new public roof garden on Fenchurch Street, 15 floors up, in the heart of the City of London.
March 2019
In mid-March a copy of the report finally arrived by post, printed in full colour. Whilst fascinating, I struggled to understand what the selected images were showing. The reported transit times were : 15 minutes to pass through the stomach; 3 hours travelling in the small bowel; and 9 hours to leaving the colon – all classed as being “within average range”. At the front there was a summary report. It contained those words I was expecting but didn’t want to see “…with a background of Crohn’s these are in keeping with mild to moderate active disease”.
The downside of the VCE procedure is waiting for the video to be analysed by a gastroenterologist. With a conventional scoping the report is available immediately afterwards. The capsule that I swallowed took 6 images per second. With a transit time of approximately 3 hours, through the small bowel alone, this produced around 65,000 images. When you add in the stomach and large bowel you realise the scale of the task. I have since been told that it takes anything from an hour upwards, depending upon the playback rate selected. I was surprised it wasn’t considerably longer.
The date for the gastro appointment came through – 15th April. I wanted to be well prepared and started jotting down questions. By the time I had finished the list was impressively long.
Monday 15th April 2019 – Guy’s Hospital – Gastroenterology
The gastro clinic has been a victim of its own success. Once a patient gets referred there they invariably don’t want to return to their original hospital. I guessed they must have been overbooking to cope with the numbers and as a result, clinics usually run late. I made sure I took something to read with me. Having registered with reception I settled down with the book. A nurse appeared and apologised that the doctors were running 75 minutes late! I wondered if there would be time to go and have the chest x-ray done. It was worth a try. Ten minutes later I was back in the outpatients’ waiting area with the x-ray completed.
I asked the nurse to put a note on my folder that I wished to see my usual doctor. After a few minutes he was calling my name. I entered the consulting room with list in hand as an aide-memoire.
He asked “have you received a copy of the VCE report?” Yes, but didn’t know what I was looking at. He worked his way through the document stopping at any frames of interest – “that looks like an ulcer, and there, and that’s one…..”. This explained the conclusion of “mild to moderate inflammation”. I asked whether it was possible to work out the location as I had been getting an ache across my midriff, just above my navel. Could it be connected? He thought it more likely to be my hernia causing the pain in that location.
Next we went through the results of the recent blood test. “You’ve had chickenpox but not glandular fever as no antibodies are present, and you haven’t got AIDS, but you probably knew that”. I remembered having chickenpox as a child but I had also suffered a very bad bout of glandular fever at the beginning of my ‘A’ levels (my excuse for doing so badly). Maybe antibodies disappear over time?
I was pleased to see that my Hb had risen slightly to 11.8. Another test, looking at protein bands, was marked “insufficient sample provided” which didn’t make sense given the number of phials the phlebotomist had taken. I would need to give a further sample after the appointment.
I outlined my reticence about starting vedo, or any drug for that matter. Having managed without any Crohn’s medication for nearly 8 years I would be hesitant to restart. I knew that other patients had suffered side effects when on MABs and wondered if I would be more susceptible due to my co-morbidities? He told me not to be concerned and that I must be made of “stern stuff” as there were many patients at my age who were in a considerably worse state! The side effect profile of vedo was proving to be good and its action very successful. Recent research into its use with UC, showed better results than expected.
What could happen if I decided not to start Crohn’s drugs? The worst outcome would be the inflammation becoming so advanced that the bowel perforated, or formed fistulas, resulting in an emergency operation. Given that I should try to avoid surgery of any kind this sounded like a risk too far.
There was also the practical consideration of having to make regular visits to London for infusions. Whilst I liked those trips, at present, I might not be so keen as I got older. Would it be possible to have them carried out at my local hospital? He replied that it might not be necessary as a patient administered version of vedo had been developed, using compressed air to deliver the doses rather than a needle, and was currently undergoing trials. If they proved successful then in 2 or 3 years time it might be possible to replace some infusions.
I asked if, in hindsight, I should have had a capsule endoscopy sooner than October 2018 as the calprotectin results suggested the inflammation started early in 2016. He responded that the first place to look following raised calprotectin results is the large bowel. Two colonoscopies showed nothing and the subsequent small bowel MRI also showed no inflammation. However, given my experience, he was now favouring earlier intervention with a capsule endoscopy.
My final question was how would we determine if the drug was working given that I felt no physical symptoms? Regular calprotectin tests throughout the year and at the end of twelve months there would be a follow-up VCE and small bowel MRI. The one thing I forgot to clarify was whether vedo is continued as a maintenance dose once remission has been achieved.
I still wanted to discuss the situation with my wife before making the final decision but was leaving the consultation with a lot more positive thoughts than when it started. How would I give the go ahead? “Contact the IBD Helpline and take it from there.” With that we shook hands, I bade him farewell and headed for the blood test room.
Having weighed up the pros and cons, and with the additional imperative of avoiding surgery, if at all possible, it seemed to be a no-brainer that I should at least try vedo to induce remission before my gut suffered from serious damage. I emailed the IBD Helpline with my decision.
The next day they rang to arrange the first infusion. “Vedo days” were Wednesdays and Fridays. As luck would have it there was already a haematology appointment arranged for the last Wednesday in May so the infusion was booked for an hour later on the basis that haematology clinics usually run to time.
Monoclonal Antibodies (MABs)
MABs are antibodies that are made by identical immune cells, all clones of a unique parent cell. My brief flirtation with Infliximab, in 2009, only lasted for three doses as I showed no signs of improvement, but, to be honest, my condition had progressed too far for any drug to have made a difference. At that point MABs had already been in use for a decade and in the following years there has been a great deal of research work for their use in multiple areas of medicine. Many had subsequently been licenced to treat Crohn’s Disease but they are neither cheap to develop or manufacture and this is reflected in the high cost of each dose.
Vedolizumab (Entyvio) was launched in 2014, and developed specifically for IBD treatment. It was the first non-TNF (Tumour Necrosis Factor) inhibitor and works by blocking a protein on the surface of white blood cells that cause the inflammation in Crohn’s disease…..and selectively inhibits leucocyte migration into the gut!
….and, no, yet again, I didn’t know what that meant. Being a non Anti-TNF drug apparently made it more suitable for older patients, starting biologic therapy for the first time, and being gut specific it appears to have less risk of side effects. The usual pattern of infusions is to have them at Week 0, 2, 6 and then at eight weekly intervals. It usually takes four or five infusions to show if it is effective although it is known that Vedolizumab can take a lot longer to become effective.
Wednesday 29th May 2019 – IBD Infusion Unit – Guy’s Hospital – First Infusion
My aim had been to kill two birds with one stone by combining the planned haematology appointment with my first infusion. It turned out that the appointment had been cancelled due to the consultant being away. I took advantage of the free time to take a walk along the Thames and then a quick visit to Tate Modern to use their “facilities”. As a Crohn’s patient, or maybe as the ageing process quickens, the location and quality of public conveniences becomes of great interest.)
I arrived at the Unit with a couple of minutes to spare and handed in my baseline calprotectin sample. Future readings would be measured against this result to assess the effectiveness of the new drug.
I was shown to one of the infusion chairs. A nurse came over to introduce himself. He worked for Takeda, the manufactures of vedo, and provided additional help in the unit on “vedo” days. He asked the usual questions: “what medications are you on?”; “are you allergic to anything?”; “how are you feeling?” etc. He measured my blood pressure, oxygen saturation and temperature, inserted a cannula and took some blood samples.
I was expecting the procedure to take several hours. Was that realistic? The nurse replied that there would be a “30 minutes infusion followed by the same for a saline flush”. I subsequently learnt that the flush had a secondary purpose of allowing the nurses to keep an eye on the patient after the infusion to check for any signs of an adverse reaction.
The drug is supplied in powder form and reconstituted once the patient arrives to avoid wasting such an expensive drug if there was a “no show”. Once mixing was complete I had the vedo connected and flow rate set. I settled down with the book I was reading about heart surgery. As Crohn’s patients we go through some fairly challenging experiences and witness some gory sights but I even found myself squirming at the surgeon’s descriptions. Luckily there were no photographs!
With the vedo finished it was swapped with the saline flush and I went back to my book. Allowing 30 minutes for the paperwork, tests and preparation, the whole procedure was completed in about an hour and a half. The nurse warned me that I might feel more fatigued than usual. Time would tell.
Infusion No.2 took place two weeks later. It was preceded by the rebooked haematology appointment which, to borrow a medical term, was “unremarkable”. Very much routine.
By the end of 2019 I had reached my fifth infusion and was due the sixth just two days into the New Year. In mid-September, when I went in for the fourth dose I handed in a sample for calprotectin testing. The result would show the effect of the first three infusions. The level had dropped from 1790 to 472. Impressive but still high. I had another calprotectin test at the end of October. This also showed a decrease, to 439 then 435, but the trend had now levelled out. During my fourth visit to the Unit the lead Nurse was explaining that there had been a huge growth in the number of patients they now infused. The clinic had started out with a session just once a week but this had rapidly expanded and now they gave a full five day service. With the cost of the MABs being so high I wondered how this growth in usage was impacting upon the NHS budget.
I happened to mention that I had dates booked for some teeth extractions. This clearly rang alarm bells. The rule, when on other MABs, was to avoid any surgery in the period two weeks either side of the infusion. She would check with the doctors to see if this applied to vedo. I received an email later confirming that I should keep to the same restriction and ended up having to rearrange the dental appointments accordingly as infusions take precedence.
What’s a VBIC?
In early July a letter arrived from one of Guy’s VBIC consultants. I was intrigued as it was not an abbreviation I had come across before. Online I found a GSTT document explaining that it stood for “Virtual Biologics & Immunosuppressants Clinic, a multi-disciplinary meeting, held at regular intervals, to review patients on biologics and other high cost drugs. After each infusion, blood test results and calprotectin, if available, are discussed”.
The VBIC letter mentioned that the blood test showed normocytic anaemia which translated to normal-sized red blood cells, but a low number of them. It was noted that I was taking iron supplements but suggested that iron infusions should be considered if the condition got worse.
The next letter followed the large drop in calprotectin level. That was somewhat reassuring but clearly there was a long way to go to reach 50 or below. The VBIC was suggesting that further testing, probably in the form of another VCE, should be carried out to “gather some further objective evidence in the coming months”.
The letter also mentioned that I had relatively stable pancytopenia which meant that I now had low counts for all three types of blood cells: red, white, and platelets. It is usually due to a problem with the bone marrow that produces the blood cells. Could this also be laid at the feet of the Azathioprine? Should I expect another bone marrow biopsy to be arranged, as suggested by the haematologist?
Monday 14th October 2019 – Guy’s Hospital – Gastroenterology
I had been forewarned that my usual consultant was moving on from the Monday clinic to a Tuesday afternoon over at St.Thomas’ but it was unclear when the change would take place.
Having been through the usual waiting room shuffle I heard my name being called by a new doctor. As usual I explained that I would like to see “my” consultant. He replied that the changeover to Tuesdays had started that week.
As I was not at a key decision point in my Crohn’s treatment I had already decided that seeing another doctor would not be an issue and maybe it would be good to hear another consultant’s view of my case. I have found in the past that a different doctor may make a comment that gives a slightly different angle on my ailments that, in turn, gives me a better understanding. It takes me a little nearer to achieving my goal of mapping how the various co-morbidities inter-relate and their potential causes.
The other benefit of sometimes seeing a new doctor is that it gives some of the less experienced ones exposure to the more interesting or complex cases.
We discussed how I felt following four vedo infusions. I explained that all was well apart from seemingly being more tired, He was reassured by the latest calprotectin result dropping from 1790 to 472 but this was clearly still abnormal.
I mentioned my concern that my Hb level was low despite doubling the dose of iron tablets, suggested by my GP. He thought it would be worth seeing if an iron infusion would increase my haemeglobin. He would make the necessary arrangements.
The next day I had a telephone call from the IBD infusion unit. “When would you like to come in for the iron? Can you make it next Tuesday?” The arrangement was made. After the infusion was complete I was told that, since my weight had increased, I could have a further unit in a week’s time. It also gave me the opportunity to take in another sample for calprotectin testing. In the space of two weeks I had been for three visits, two iron and one vedo. I was starting to feel like a “regular” and the nurses were greeting me like an old friend.
The result of that calprotectin test also showed a decrease to 439 but the trend had slowed considerably. What did this indicate? Was it to be expected? Had the vedo stopped working? The first result of 2020 had only dropped a further 4 to 435.
I found an extract from a research trial – “…..patients should be aware of the somewhat gradual and incremental beneficial effect of vedolizumab, meaning that responders may expect further improvement in clinical disease activity beyond week 14 of treatment”. My calprotectin had dropped dramatically to start with but then seemed to plateau at around the 430 mark.
Tuesday 18th December 2019 – St.Thomas’ – Endoscopy Department
It was time for the yearly trip to Harrods Food Hall to buy some Christmas treats before heading over to St.Thomas’ early afternoon for an upper GI endoscopy. This would be my twelfth, but who’s counting. The procedure followed the same pattern as last year with the exception of a new doctor driving the scope. For the fifth year running no banding was required, so no need for a sloppy diet in the lead-up to Christmas. A good end to the year and reasons to being looking forward to 2020.