As you are aware, access to a modern oesophageal testing lab had been available through our private rooms for well over 6 months. This has assisted us in diagnosing problematic patients who are thought to have “reflux” but have not followed the script in terms of response to conventional medications. This update will help GPs interpret the results which, at times, can be quite technical.

Patient 1: Typical reflux symptoms responsive to PPIs

This patients has typical acid reflux symptoms but required high doses of PPI, sometimes with concurrent antacids or prokinetic agents, to help with breakthrough symptoms. An oesophageal study was performed to reveal normal manometry (ruling out dysmotility conditions which are a contraindication to anti-reflux surgery). A Bravo capsule was deployed endoscopically (a pH sensor within a disposable capsule which is attached to the lower oesophageal mucosa with a pin and detaches within a few days). This captures significant reflux episodes with GOOD CORRELATION with patient symptoms. This patient was referred for a fundoplication and achieved excellent symptomatic relief with only occasional use of PPIs.

Patient 2: Typical acid reflux symptoms unresponsive to PPIs+ prokinetic agents

Oesophageal testing is very important for these patients as they have had no response to maximal medical therapy for reflux. Oesophageal manometry was normal. Oesophageal pH did not show significant reflux episodes and there was no correlation with patient symptoms. These patients probably have “hypersensitive oesophagus” – that is they experience typical symptoms of acid reflux without the prerequisite stimulus of a low enough pH. These patients can be very difficult to treat and respond poorly to fundoplication and therefore should not be pushed down the surgical pathway. They are probably best treated as “chronic pain” patients with CBT, lifestyle modifications (essentially weight loss if BMI is over 25), food elimination if a food diary is useful for symptom production and a trial of pain modulators such as Tricyclic Antidepressants (TCA) like nortryptilline.

In our next instalment on interpreting oesophageal tests, we will discuss other clinical problems such as Laryngopharyngeal Reflux (LPR) and volume reflux.

Advances in molecular biology, immunology, and drug development since the late 1990s have led to a variety of new treatment approaches to IBD and other systemic inflammatory diseases associated with autoimmunity. An overview of the drugs (current and new) available to our IBD patients on the PBS will be reviewed here.

TNF Inhibition

The first drug to be available was the TNF (Tumour Necrosis Factor) inhibitor Infliximab. This drug is still the preferred first line therapy for severe acute UC (ulcerative colitis) particularly in a situation where colectomy is to be avoided.

A work up for TB, viral hepatitis, varicella immunity and previous EBV/CMV is required as reactivation can be a problem.

Infliximab and it’s biosimilars are chimeric murine (mouse)/human anti-TNF antibodies and suffer from the formation of anti-drug antibodies (ADA). Where possible, it should be used with 6 months of overlapping immunomodulators such as the thiopurines to minimize the development of drug-neutralising ADA. Currently it is an IV only preparation but trials are being conducted on it’s efficacy as a subcutaneous injection.

Adalimumab (Humira) and Golimumab (Simponi) are human or humanized anti-TNF antibodies. The suffer from similar adverse effects and neutralizing ADA are also seen in these agents. They are given subcutaneously. Golimumab is only approved for UC

Side effects

Autoimmune diseases can occur in a small percentage of patients despite the commonly noted increase in autoantibodies. The majority of these cases are vasculitic syndromes particularly cutaneous vasculitis, lupus like syndromes and psoriatic skin changes. Treatment is changing to another class or biologics but some patients may require specific targeting of the complication autoimmune manifestation.

Anti IL (interleukin) Drugs

Ustekinumab (Stelara) is an IL-12/23 antibody PBS approved for use only in CD in Australia. It can be used as primary monotherapy or after failed anti-TNFa but in conjunction with an immunomodulator. It is given subcutaneously after IV induction.

Anti-integrin Antibody

Vedolizumab (Entyvio) is a humanized anti-alpha-4-beta-7 monoclonal antibody. It can be used as first like therapy for both UC and CD, or second line therapy with concurrent use of immunomodulators if ADA were present. It is given intravenously. PML (progressive multifocal leukoencephalopathy caused by reactivation of JC virus) is a theoretical risk and should be screened if unusual neurological symptoms occur.

Small Molecules: The Game Changer?

Tofacitinib (Xeljanz, Pfizer), an oral small molecule Janus kinase (JAK) inhibitor, is used for treating adults with moderate to severe UC who have failed or are intolerant to anti-TNF agent-based therapy outside of Australia. As of July 2021, this drug is now PBS approved for initial and maintenance treatment of UC (Not for CD yet).

Advantages

• Oral induction and maintenance

• Effective for primary and secondary non-responders to anti-TNF drugs

What to look out for

Increased risk of reactivation of Herpes Zoster: It is recommended all patients are treated with Shingrix before starting Tofacitinib.

Increased risk of DVTs in East Asians. In these patients with a history of vascular thromboses, an alternative agent should be considered.

Lipids: If LDL/HDL ratio is increasing, usual treatment of hyperlipidaemia applies

Raised CK: Due to reduced renal excretion of CK and is NOT a myopathy. Not of concern.

Elevated LFTs: This is of no clinical significance. It does not generally cause hepatic toxicity.

Low WCC: All immune-modulators cause this, and is of little clinical significance with this drug.

Pregnancy: Not currently approved for use for pregnant women or those wishing to conceive. Switch to a TNFa if a drug is required for cover.

Treatment Algorithm

My first line biologic treatment for CD at the moment is Adalimub due to its ease of administration (subcutaneous). These patients are generally already on immunomodulators, so I would overlap them by 6 months before ceasing the immunomodulator.

My first line treatment for UC is now Tofacitinib for the reasons stated in this newsletter.

My second line for CD is to use a non-antiTNFa drug such as Ustekinumab (the subcutaneous administration by the patient sways me)

My second line for UC is a non-antiTNFa drug such as Vedolizumab. TNF-a drugs can still be used if there was failure
of small molecule drugs.

Dr John Ombiga talks about his approach to weight loss through the Low Carbohydate Healthy Fat (LCHF) diet. This is usually in the context of patients referred for management of Non-Alcoholic SteatoHepatitis (NASH or Fatty Liver) and strategies to assist in obesity related reflux (which is the majority of cases in our community).

“Does this sound familiar? You’ve switched to a low-carb (LC) or keto diet for management of fatty liver disease ortype 2 diabetes and metabolic syndrome. You’d read all about the benefits others have experienced—weight loss, increased mental clarity, more energy, better digestion—and you were eager to get started.

But after a couple of days, you started to feel terrible. You began to experience the “keto flu”—fatigue, crankiness, decreased physical performance, cramping, and brain fog.

This is all too common in our patients who adopt LC or keto diets. Does that mean you should start eating more carbs? Sometimes it does. Low carb and keto diets aren’t for everyone. But other times, adding carbs back in isn’t the answer.

What can help? Electrolytes.

When you switch to an LC diet, you are probably eliminating processed foods from your diet, which contain high amounts of sodium. What’s more LC diets make the kidneys excrete electrolytes at a higher rate. This is normal and not something to be worried about, but it is important to replace these electrolytes. This means that many people who adopt LC or keto diets end up with a deficiency of electrolytes—magnesium, potassium, and especially sodium –and this is what causes the “LC/keto flu.”

Over the last 50 years, we’ve been hounded to reduce our sodium intake. Yet recent studies have shown not only that sodium restriction is ineffective in reducing the risk of cardiovascular disease, but it may even increase the risk! A 2011 study published in the Journal of the American Medical Association found that people eating two grams or less of sodium per day experienced a significantly higher risk of cardiovascular events than those eating five grams per day—which is double the amount of sodium recommended by groups like the American Heart Association. And this study was done in people following a typical diet, not LC or keto. This is even more true if you’re physically active. Vigorous exercise can lead to sodium loss (through sweat) as high as 3,500 to 7,000 mg per day!

How do you fix this problem? Drinking Gatorade or other sports drinks isn’t the answer. These products are typically high in sugar and woefully lacking in the electrolytes you need to replace.

For example, Gatorade has 29,000 mg of sugar (!), but only 230 mg of sodium, 65 mg of potassium, and 0 mg of magnesium. A simple electrolyte drink can be made with 1 scoop of Magnesium powder, ½ teaspoon of pink salt, ½ teaspoon of cream of tartar (Potassium citrate) in 600-800ml of water. Some people add a tablespoon of apple cider vinegar for taste.