‘The P in prednisone stands for poison’

5 minute read

It’s been more than a decade since Dr Michelle Petri’s famous declaration, and research presented at ACR 2023 bolsters the assertion.

At Rheumatology Republic’s post-ACR webinar, Dr Claire Owen was tasked with discussing some of the giant cell arteritis and polymyalgia rheumatica research presented at ACR 2023.

“The meeting was a bit light on for PMR abstracts this year, but it did make an appearance in The Great Debate, which involved Dr Philip Seo and Dr Robert Spiera,” said Dr Owen.

“Philip Seo was arguing for the early introduction of biologic agents in PMR, as well as in GCA. Of course, I think we’re more convinced of the evidence in the latter.

“Philip’s main arguments were that one, biologics work and two, steroids are bad, but some of the data that he presented during this presentation is quite new.”

In his presentation, Dr Seo referenced Dr Michelle Petri’s quote, “The P in prednisone stands for poison”.

Stated more than decade ago in the context of lupus and cardiovascular events, Dr Seo provided a compelling argument that prednisone is still overused in many rheumatological conditions, while the list of negative side effects continues to grow, including for low-dose prednisone.

“Data from the ACR RISE registry has demonstrated frequent relapses in PMR after 12 months, and the vast majority of patients are still taking glucocorticoid therapy after 12 to 24 months,” said Dr Owen as she highlighted some of the data Dr Seo presented.

“I think as rheumatologists, we’ve often thought that five milligrams or less of prednisone is fairly harmless. But cardiovascular risk data from a very large population study of patients with immune-mediated inflammatory diseases suggests significant increased risk of MACE amongst patients who are treated with low doses of glucocorticoid therapy.

“Philip also drew our attention to the fact that the most recent EULAR/ACR guidelines have changed regarding surveillance for glucocorticoid-induced osteoporosis, which now begins at 2.5 milligrams prednisone daily.

“And, in RA, there’s a EULAR recommendation that steroids shouldn’t be used for more than three months,” said Dr Owen.

While bone density and cardiovascular effects have been known for a while, research on central nervous system effects is relatively new, and Dr Seo mentioned a large cross-sectional study, published in the BMJ last year, demonstrating significant changes in brain volume and white matter among patients treated with systemic and inhaled steroids.

The study authors suggested that the association “may contribute to the neuropsychiatric side effects of glucocorticoid medication, especially with chronic use”.

“Why is this of relevance and why have I flagged it?” said Dr Owen.

“Well, because out on the poster floor was this very neat work from an Irish group (poster 0720) demonstrating a very high rate of cognitive dysfunction amongst patients with polymyalgia rheumatica.”

When recruited, the 51 patients were in clinical remission on a stable dose of glucocorticoid therapy, and it was at least three months but less than 12 months since the initial PMR diagnosis.

“And yet, what they found was that 70% of them met the definition of cognitive impairment using the MoCA [Montreal Cognitive Assessment] test. By comparison, around 13% of patients in this age group should meet the definition of cognitive impairment,” said Dr Owen.

“So I think that put together this really makes us question how safe that low-dose prednisolone really is. And I think it’s pretty clear now with all the available evidence that PMR is not a monophasic disease.”

In the webinar panel discussion after Dr Owen’s presentation, moderator Dr Irwin Lim remarked “the prednisone data was really disturbing”, particularly the cognitive impairment research.

“I’m inheriting lots of patients at the moment who are coming in with five milligrams over 10-20 years. And it’s impossible to get them off, I mean you try and try,” said Dr Lim, who then asked the panellists what they do in such cases.

“GPs are very liberal with their dose of prednisone, half our patients already come on prednisone,” said Professor Peter Nash.

He stated that instead of prescribing oral prednisone, patients should get an intramuscular or subcutaneous bridging dose while they start out with methotrexate or other DMARDs.

“Once they get the bottle, every time they flare, they take a handful, then they’ll stop and they’ll flare a week later, they’re on the roller coaster.

“I think if they don’t start, you’ve saved them a lot of trouble,” said Professor Nash.

Professor Rebecca Grainger concurred, saying they used to use that approach, though staff resourcing constraints made it difficult.

She added that if you look at any study, about 20% of people with rheumatoid arthritis are on prednisone.

“It’s pretty consistent, actually, across North America, Canada, and even in New Zealand, all my audits and our own practice here in Wellington. It’s about 20%. It’s a tough nut to crack.”

Dr David Liew mentioned research presented in one of the ACR plenary sessions on cardiovascular risk and low dose prednisone in RA based on VA administrative data (abstract 2430).

“GC doses as small as 5mg/day, durations as short as 30 days, and use as long as one year prior to MACE were all associated with an increased risk of MACE,” wrote the authors.

While that’s in rheumatoid arthritis, other patient groups are also affected, and Dr Owen pointed out it’s particularly problematic in the context of PMR where there’s very limited other options.

 “I think this really just speaks to the fact that we shouldn’t be accepting glucocorticoid monotherapy as appropriate for any of our diseases,” said Dr Owen.

Rheumatology Republic’s post-ACR webinar, The abstracts that will change practice was held on Tuesday 21 November, featuring Professor Peter Nash, Dr Claire Owen, Professor Rebecca Grainger and Dr David Liew. You can register here to watch a recording.

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