14 December 2023

Top 10 clinical stories for 2023

Clinical

Shingrix shortages, opioids for back pain and pizza-led RA treatment were hot talking points this year – but what else made headlines?

Here are some of the top stories from Rheumatology Republic and our sister publications over the last 12 months.

This is why we can’t have nice things (Part 1): Mounjaro

Way back in February the TGA announced its approval for tirzepatide (Mounjaro) in the treatment of insufficiently controlled type 2 diabetes, following previous approvals for semaglutide (Ozempic) and dulaglutide (Trulicity).

Following the announcement, Associate Professor Sof Andrikopoulos, CEO of the Australian Diabetes Society, hoped PBAC would add Mounjaro to the PBS in a timely, but these hopes were dashed when an application from manufacturer Eli Lilly was rejected in July.

Despite getting the thumbs down from PBAC, Eli Lilly announced Mounjaro would be available as a private script from September, launching the product at the 2023 Australasian Diabetes Congress.

The buzz surrounding Mounjaro continued to grow throughout 2023, peaking last month when a preprint suggested it was more effective than Ozempic with respect to weight loss, particularly over a 12-month period.

But the buzz ceased somewhat earlier this month when the TGA announced all strengths of Mounjaro would be in short supply until at least August next year, citing higher-than expected demand for the drug, which, like Ozempic, has gained popularity around the world as an off-label therapy for weight loss.

Have two slices of pizza and call me in the morning

The title of tastiest study of the year goes to a group of Italian researchers (I mean, who else?) who found eating at least four slices of pizza once a week reduced rheumatoid arthritis disease activity by a whopping 70% compared with people who only ate pizza once or twice a month.

“These beneficial effects were likely driven by mozzarella cheese and, to a lesser extent, by olive oil, even though we were unable to assess the possible contribution of tomato sauce,” they concluded.

The researchers were quick to point out that just any old pizza won’t bring about the same benefits, so think twice about ordering from Domino’s or some other multinational chain outlet.

“Within Italian tradition, pizza is a stand-alone meal, usually made from fresh, high-quality ingredients [that] generally balances carbohydrates, proteins and fats well. Outside Italy, pizza generally belongs to a “Western-like” dietary pattern, along with other junk foods,” they said.

The CAR T-cell revolution continues

CAR T-cell therapy for autoimmune diseases continued to amaze, with case studies on the successful treatment of refractory antisynthetase syndrome and severe refractory systemic sclerosis published earlier in the year.

Meanwhile, follow-up data on the SLE patients who received CD19-depleting CAR T-cell therapy was presented at EULAR 2023 by Professor Georg Schett.

A total of seven patients with severe refractory SLE were given a single CAR T-cell dose and went into disease remission after treatment, with the latest data showing all seven have maintained remission over varying follow-up times ranging from four months to two years.

At ACR Convergence 2023, Professor Schett’s team presented data on the successful treatment of two additional cases of systemic sclerosis and two additional cases of antisynthetase syndrome, including follow up on the original cases.

News that the FDA was investigating reports of malignancies, including CAR-positive lymphoma, following cancer treatment with several products in the class, caused something of a ripple a few weeks ago.

However, the number of cases reported was very small and the implications for CAR T-cell therapy used in autoimmune diseases are unclear.

This is why we can’t have nice things (Part 2): Shingrix

PBAC’s decision for Shingrix to replace the Zostavax vaccine on the National Immunisation Program – while also making it available to an increased range of patients – was met with welcome arms following the announcement in August.

The decision meant almost five million Australians would be able to access the vaccine for free from 1 November, including:

  • All people aged 65 and over
  • First Nations people aged 50 and over, and
  • Some immunocompromised people 18 years and over.

However, disconnect between the federal government (who supply the vaccine) and the state and territory health departments (who distribute the vaccine) meant the Shingrix rollout hit a roadblock before it even got going.

Dr Rod Pearce, chair of the of Immunisation Coalition, was one of many clinicians to express frustration over the bungled transition.

“It’s a very frustrating part of this rollout but it’s also inherently built into the way Australia rolls out vaccines,” he told TMR in November.

The DoHAC denied there was a shortage of vaccines, stating they expected 1.6 million Shingrix doses to be distributed between November and the end of June next year, with half a million of these doses to be delivered to providers before we ring in the new year.

Meanwhile, the exclusion of people experiencing immunocompromise due to use of immunosuppressants used in rheumatology was disappointing.

In a letter to membership, the Australian Rheumatology Association advised that it has approached PBAC proposing expanded eligibility for rheumatology patients taking medications likely to leave them immunocompromised and at risk of herpes zoster infection.

Opioids for back pain: yay or nay?

In June the OPAL study challenged clinical practice guidelines, suggesting opioids should no longer be considered for the treatment of acute back pain.

Associate Professor Michael Vagg, a Melbourne-based pain medicine specialist, told The Medical Republic the researchers were trying to inappropriately generalise their results.

“They studied oxycodone and naloxone in a modified-release formulation. But modified-use opioids have never been on-label for use in acute pain and they are not recommended as such and have not ever been PBS-listed for such.

“In layman’s terms, they’ve done a study where they tried to look at doing push-ups to help with back pain and then they’ve decided that all exercise is no good for the back pain,” he said earlier this year.

The OPAL authors, led by Dr Caitlin Jones, penned a response to the comments from Professor Vagg, stating the regular doses of modified-release opioids achieve comparable concentrations to immediate-release opioids within the first 48 hours.

“This is important as our treatment period was weeks, not hours. The benefits of the modified-release oxycodone/naloxone formulation (better adherence, less constipation, maintaining blinding) outweighed the downside of not being able to titrate the dose as quickly compared to an immediate-release formulation,” they wrote.

Meanwhile, an overview of seven Cochrane reviews (published in the Cochrane Database of Systematic Reviews) failed to find any evidence opioids were beneficial in acute back pain.

There was, however, some evidence suggesting certain opioids (tapentadol and buprenorphine) were effective for treating chronic low back pain.

A CVD risk calculator in your pocket

July saw the release of an Australian-specific cardiovascular disease risk calculator, along with the first update to prevention guidelines in a decade.

The AusCVDRisk calculator replaces the previous algorithm which was developed using data from one town in the United States more than 50 years ago.

The risk assessment is recommended for the following groups of individuals without a known history of atherosclerotic cardiovascular disease:

  • All people aged 45-79 years
  • People with diabetes aged 35-79 years, and
  • First Nations people aged 30-79 years.

The calculator estimates the likelihood of an individual being hospitalised or dying from cardiovascular disease over a five-year period as either low (< 5%), intermediate (5-10%) or high (10% or more). Future assessment and management strategies are recommended based on the calculated risk.

The calculator also allows clinicians to include risk factors, such as coronary calcium score and the patient’s family history, as optional extras in addition to things such as age, sex, smoking status, blood pressure and postcode.

“The cardiovascular disease calculator is the new gold standard in assessing the risk of cardiovascular disease in Australians, [and the] new guidelines will help medical professionals across the country to provide earlier detection and treatment for the disease, bringing new hope and help to thousands of Australians,” Health Minister Mark Butler said at the launch.

This is why we can’t have nice things (Part 3): ADHD medication

Lisdesamfetamine (Vyvanse, Takeda), a popular ADHD drug, also joined the shortages party in 2023.

At the time of publishing, the TGA’s Medicine Shortage Reports Database lists the 30mg and 50mg capsules as having limited availability, with supplies expected to arrive in March next year.

The 20mg capsules are anticipated to be in shortage from 18 December.

Associate Professor John Kramer, chair of the RACGP’s specific interest group on ADHD, ASD and neurodiversity, was frustrated by the announcement, but recommended an interesting strategy to help patients deal with shortages over the coming months.

Professor Kramer’s advice involves breaking up a larger dose and mixing it in water, which can then be consumed over the course of two days. For example, a 60mg dose dissolved in 10ml of water turns into two 30ml doses (in 5ml of water).

The approach is safe and has backing from pharmacists and biochemists, according to Professor Kramer.

DIY cervical screening tests

Self-collected cervical screening tests experienced a Taylor Swift-esque explosion in popularity this year, with Medicare data released in June showing a 13-fold increase in the number of completed self-tests compared to the previous 12 months.

The Northern Territory, Tasmania and South Australia were the biggest adopters of cervical self-screening, with the ACT and NSW being slower on the uptake.  

The eligibility criteria for self-screening were expanded in July last year to include all sexually active cervix owners aged 25 to 74, rather than those who had never been screened, or had been under-screened compared to other women of a similar age.

Professor Julia Brotherton, professor of cancer prevention policy and implementation at the University of Melbourne, told TMR self-collected tests were as accurate as provider collected tests and provided and increased level of comfort for patients.

“Overall self-collection is highly acceptable to patients across the socioeconomic spectrum and our research and that of others in Australia and internationally shows it is acceptable across culturally diverse groups,” she said.

The latest AIHW data indicates one in ten cervical screening tests are positive for an oncogenic type of HPV.

The 17 most important factors predicting dementia

In April the University of New South Wales and Neuroscience Research Australia (NeuRA) published results validating CogDrisk, their dementia risk prediction tool, in four separate and international cohorts of patients.

As the name implies, CogDrisk assesses 17 individual risk factors for dementia and Alzheimer’s disease, including BMI, hypertension, cholesterol, engagement with physical and cognitively stimulating activity, loneliness and the amount of fish you consume each week.

“There’s lots of information about the risk factors for dementia in the academic literature. But there’s a gap between just knowing the risks and actually being able to assess whether or not you have the risk, and then knowing what to do about it. CogDrisk was developed to address this,” Professor Kaarin Anstey, the study’s lead author, told media earlier in the year.

The CogDrisk tool is freely available online and can be completed by anyone aged 18 years and older. The tool develops a personalised risk profile highlighting factors relevant to the individual and provides strategies to target these specific factors. The whole process takes about 20 minutes.

These aren’t your grandparent’s constipation treatments

There was movement among gastroenterology circles in May when the American Gastroenterological Association and the American College of Gastroenterology released a new set of pharmacological treatment guidelines for constipation in adults.

Strong recommendations were made for the osmotic laxative polyethylene glycol (Macrogol, Movicol), the stimulant laxative bisacodyl (Dulcolax) and sodium picosulfate (Dulcolax SP drops).

Associate Professor Rebecca Burgell, a gastroenterologist from Alfred Health, told TMR the recommended products were safe to use on a daily basis, and that using them as per the doctor’s orders would not damage the bowel.

“When a patient that has chronic constipation and needs a stimulant laxative every day, that is not the end of the world. But if that patient started increasing and increasing the doses, having loose stools, having other complications, that’s when it becomes a problem,” she said.

In contrast, there was limited and uncertain evidence on bran, and no mention of prunes.

Australia does not currently have official guidelines for treating constipation, although Therapeutics Guidelines offer some evidence-based advice (for a price).

Additional reporting by Karina Bray.