How To Be A Better Mountain Medic ... Infliximab and UC

Posted by Jeremy Windsor on Oct 27, 2019

Earlier this year we were contacted by a 32 year old man seeking advice prior to a two week charity trek to Kilimanjaro. Ten years earlier he had been diagnosed with Ulcerative Colitis (UC). Unfortunately his condition had not been easy to manage - a series of abscesses and fistulae had led to long hospital stays and extensive surgery. However in 2016 he was started on infliximab and his symptoms had dramatically improved. He had been free from "flare up's" and not needed any other medication for more than two years. In fact, during this time he had returned to work, successfully walked the Pennine Way and climbed more than 50 Munros!

We got in touch with Drs Grace Hatton and Niall Van Someren for their advice. First, here's Dr Hatton with some background on UC and the role infliximab plays in treating this life-threatening condition...

"UC is a disease in which the body’s immune system attacks the cells that line the large bowel. It starts in the rectum and extends proximally into the large bowel. UC affects more than 300,000 people in the UK. Unfortunately, the incidence is growing with around 10 new cases being diagnosed in every 100,000 people each year. What causes UC is unclear. However a combination of genetic and environmental factors is largely thought to be responsible. Whilst patients spend long periods of time in remission, “flare up's” can occur causing severe abdominal pain and bloody diarrhoea. In some cases, surgery is needed to treat abscesses, fistulae and perforations of the bowel. Patients with UC have an increased risk of developing bowel cancer.

Infliximab is a monoclonal antibody that is used to treat autoimmune conditions such as Crohn's disease, rheumatoid arthritis and ulcerative colitis. The drug works by blocking TNF-alpha, a messenger that is an essential part of the autoimmune process.

Infliximab is a protein-based drug which is derived from modified mouse tissue (hence it isn't vegan, for those of you to whom this applies!). It works by targeting inflammatory proteins that trigger UC and other related inflammatory disorders. Infliximab is unstable in the human digestive tract and cannot be given orally. An intravenous infusion should always be carried out under specialist supervision by an appropriately-trained healthcare professional. Each infusion typically lasts around 2 to 4 hours depending upon the individual's needs and local practice. Some patients may require further monitoring after the infusion in order to assess drug reactions.

Like any drug, infliximab is not without its side-effects. Although generally well tolerated, pain, skin irritation, swelling, rash, fever and - worst case scenario - anaphylaxis can occur. If mild, infusion reactions can be treated or pre-empted by administering steroids and anti-histamines. Pain relief is sometimes given to avoid discomfort during the infusion. 

Since infliximab is an immunosuppressive drug it can also predispose the individual to infection, delayed wound healing and certain cancers. 

For further information Crohn's and Colitis UK have produced a very informative leaflet.

A typical regimen, if well-tolerated, typically involves undergoing a transfusion of infliximab every 6-8 weeks for around a year, depending on patient response and local funding policies. Some patients with UC may require ‘rescue therapy’ in order to try to prevent unplanned surgery, this treatment typically lasts approximately 3 months or more. 

Infliximab is a very expensive drug, so hospitals have to apply for funding before they can use it on a patient and must review how effective it is from time to time. Those on a planned course of infliximab should be reviewed on an annual basis in order to check that the treatment is effective. In some people, infliximab can lose its effectiveness over time. To maintain remission it may be necessary to increase the dose or frequency of administration. Alternatives such adalimumab, golimumab and vedolizumab may be used instead."

The Acute Ulcerative Colitis Treatment Trial (ACT1) showed that 54%% of patients treated with infliximab maintained a clinical response at 54 weeks compared with just 20% of those treated with placebo. In practical terms, this means less medication, fewer hospital admissions and a reduction in surgical procedures. Further information can be found here.

Now here's Dr Niall Van Someren, a retired Consultant Gastroenterologist, with some very practical advice...

"Basically, infliximab is a huge advance in the therapy of inflammatory bowel disease. An infusion every 5 weeks is the usual schedule after induction of remission which uses a slightly shorter dose interval. Those pesky T cells can be kept under control indefinitely with regular infusions, although there is a feeling that infliximab can be stopped at some stage if disease markers and symptoms disappear (it is quite expensive).

Generally, other drugs such as azathioprine can be discontinued on entering remission, particularly as there has been the odd case of untreatable T cell lymphoma while taking azathioprine and infliximab.

In the case you describe, I think it would be sensible to time the pre-travel infusion to the week before travel, and since he is taking no other medication, the likeliest outcome is a symptom free trip.

The ascent profile of Kilimanjaro seems nicely conservative at 2 weeks, and he is unlikely to run into trouble from altitude problems, and it would be very unusual for altitude per se to cause a relapse.

With regard to other medications, it would be important to avoid non steroidal agents, which definitely provoke inflammatory bowel disease.  There is always a worry about infections, but I think this is generally overplayed. However, if gastrointestinal symptoms do manifest, he could have a small supply of metronidazole and ciprofloxacin, and take one of each at the start of symptoms (at the first gurgle), but only continue if there is no improvement. I suspect steroids would be of little value because he probably did not respond well prior to taking infliximab, but he may feel safer with a small amount of prednisolone in the rucksack.

With the described ascent profile, there would be no need for acetazolamide, which tends to spoil a trip anyway.  I don't think taking it would cause a relapse, but the effects on taste and sleep would make anyone miserable.

There may be a need for antimalarial prophylaxis, and this is also unlikely to affect inflammatory bowel disease.

Prolonged courses of steroids, need for operations, and requirement for infliximab would point to a severe relapse, but once in remission, patients should be normal, and live a normal active life (for example, Sir Steven Redgrave who was a successful Olympic rower despite having ulcerative colitis). I can't recall a climber though.

Some folks worry about diet affecting inflammatory bowel disease, but it does not seem to, apart from some patients reporting milk intolerance."

With this advice our trekker headed to Kilimanjaro and successfully summited the mountain. Following Niall's advice, he rearranged his infliximab infusion for the week before departure and remained symptom free throughout his trip. He is now planning a trip to Nepal!

Many thanks to Grace and Niall for their help in creating this post.

The British Mountain Medicine Society (BMMS) are organising a Science Day in the Peak District on the 13th November 2019. Why not come along? Details can be found here.

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