Taken for a ride? Guest blog by Keith Barrand
Taken for a ride?
Sometimes, when we consider veterinary products, we need to look past the glossy brochures and rep’s patter and really think about whether the product is any good. Often, the information is there but it requires some careful thought. Here are a couple of examples.
Part 1 - Semintra
Telmisartan solution (Semintra: Boehringer Ingleheim) is an oral solution licensed to reduce proteinuria in cats with chronic kidney disease (CKD). Given that proteinuria is associated with a poorer prognosis, it makes sense to try to reduce it. Telmisartan will do just that. Great!
But hang on a minute! Telmisartan reduces the amount of protein in the CKD cats’ urine but treated cats have not been shown to live any longer than similarly affected cats that are not treated with telmisartan.
This is the claim on the Semintra website:
Semintra and how does it work?
‘Semintra is an oral solution that has been specifically designed for cats and contains a medicine called telmisartan. Semintra helps to reduce the amount of protein lost in your cat’s urine. Losing too much protein in the urine is associated with a shorter life expectancy in cats suffering from chronic kidney disease.’
All these statements are, essentially, true. The reader is left to infer that reducing the level of proteinuria with Semintra will increase your CKD cat’s lifespan. There is no good evidence that it will. The website skirts around this issue very carefully.
‘After many years together, finding out that your cat has chronic kidney disease can be very distressing. The good news is that there are many reasons to remain positive. Your cat will require life-long treatment for chronic kidney disease, but many cats live happily for a number of years after diagnosis.’
It does not say that giving telmisartan will have any impact on the number of years the cat will live; just that he may live happily for a number of years.
The product even has an ISFM Easy to Give award, which looks like an endorsement. A quick check on the ISFM website shows that Boehringer is a sponsor. I have nothing against ISFM (my practice has practice membership) but this does give one reason to stop and think.
Reduction of proteinuria in cats with renal insufficiency is a ‘proxy outcome’ for the actual aim of increased lifespan. In fact, it does seem reasonable to expect that reducing proteinuria will result in improved lifespans. However, this has been found to be untrue for benazepril, another drug shown to reduce proteinuria in affected cats. Therefore, reducing proteinuria is known to be a suspect ‘proxy outcome’. If benazepril-induced proteinuria reduction has no impact on survival times, why should telmisartan-induced proteinuria reduction do so?
My reading of this is that the shortened lifespan of CKD cats with proteinuria is not being caused by the proteinuria per se, but by some other process that results in proteinuria. Telmisartan appears to reduce proteinuria but possibly has no effect on the process that is shortening lifespans.
Telmisartan has not been shown to improve CKD cats’ lifespans and there are no claims for improved quality of life so we need to ask, does it do anything useful? Perhaps, we should wait for evidence of increased lifespans before recommending this drug for our patients.
Please note: this blog refers to Semintra 4mg/ml solution (which is licensed for reducing proteinuria) and not the recently-licensed Semintra 10mg/ml solution for treating feline hypertension.
Part 2 – L4 Vaccination
In the UK, we have used bivalent vaccines against canine leptospirosis (covering Icterhaemorrhagiae and Canicola serovars) for many years. These are referred to as L2 vaccines. MSD introduced L4 vaccines (which add Grippotyphosa and Bratislava serovars) a couple of years ago. There are also other L4 vaccines including Canigen L4 and Veriscan Plus L4, as well as a trivalent vaccine, Eurican L Multi (which omits Bratislava from the mix).
MSD seem to have been quite good at persuading vets to take on L4 vaccines on a blanket-use basis. I have heard of many practices getting clients to ‘upgrade’ from L2 and I see lots of puppies coming for second vaccination after they have had L4 with their breeder’s vet.
Overall, covering two extra strains must be a good thing? Well, no actually, there are a number of problems.
Much has been made of ’10 week finish’ canine vaccinations that allow early socialisation. L4 vaccinations finish later and so vital early socialisation may be reduced. This is believed to increase the risk of behaviour problems which is a major cause of death in dogs (euthanasia due to intractable behaviour problems). Far more dogs are euthanased for this reason than die of Lepto.
VMD published figures show L4 vaccinations have an adverse reaction rate of 3.5 times that of L2 (7 per 10,000 doses compared to 2 per 10,000). There appears to be no data on differences in severity of reaction. These figures should be interpreted with caution as suspected adverse reactions in new products may be more likely to be reported.
In human medicine there is a concept of ‘number needed to treat’ e.g. how many people need to be treated with statins to prevent one heart-related fatality? We can apply this to the L2/L4 vaccine debate. So, how many dogs do we need to vaccinate with L4 instead of L2, to prevent one clinical case of leptospirosis? This is difficult to work out but is likely to be a very large number, particularly for dogs that never leave the UK (the ‘extra’ strains are more common in continental Europe).
In 2016 a vaccine scare story appeared in the national press about L4. Although overstated, vaccine scare stories reduce all vaccinations and probably increase disease incidence (not just Lepto).
Is there still a place for L4 vaccination? Yes, I believe there is. The VMD made the following statement in 2016 following an article in the Daily Telegraph wrongly suggesting that lots of dogs were dying after L4 vaccinations.
‘Careful consideration should be given as to whether the additional protection provided by vaccines containing four serovars of Leptospira versus those containing two are necessary in each individual dog, depending on their individual circumstances.'
This seems sensible advice. Dogs travelling abroad, dogs used in vermin control and hunt/point/retrieve breeds (HPR) may be at greater risk, and may benefit from L4 vaccination. However, blanket use of the vaccine, which appears to be happening in some veterinary businesses, is not good practice. Even in rural areas, I think that the majority of dogs are fine with L2.
It is important to critically appraise new products and look beyond what the manufacturer wants you to believe. Doing this means that you will not be taken for a ride.
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