Tackling multimorbidity through collaboration

As populations age, multimorbidity becomes an increasingly pertinent issue for healthcare systems. A new action group from the ABPI seeks to bring the NHS, academia and industry together to find new ways to address the problem. The Association's Dr Sheuli Porkess and Professor Janet Lord from the University of Birmingham tell us more.

Multimorbidity is an increasing issue for healthcare and the NHS. In a recent analysis of data from 2016 at the Queen Elizabeth Hospital Birmingham, 75% of unplanned admissions, which account for almost 30,000 admissions per year, were for older adults. 83% of these adults had three or more conditions. There was no dominant condition that triggered admission to hospital – although falls, delirium and breathlessness were the three most frequent.

In the hopes of raising awareness about the challenge of multimorbidity and working collaboratively to address it, the ABPI has established a Multimorbidity Action Group to develop policy and move the discussion forward – which is now open to join.

“Doctors can often see patients with a cocktail of conditions all needing treatment at the same time, with few options but to treat each condition individually with multiple medicines or other interventions, which isn’t ideal if one interacts badly with another,” says Dr Sheuli Porkess, executive director of research, medical and innovation at the ABPI. “You can inadvertently cause side effects which bring an already-ill person yet more discomfort.

“In the ABPI, we want to harness support from industry to dig into the problem of multimorbidity.  It’s a wicked problem, particularly when you consider the research process for new medicines.”

For example, the Association has entered into a new partnership with Birmingham Health Partners (BHP) – a strategic alliance between the University of Birmingham and two NHS Foundation Trusts – to tackle the biggest health challenges faced by the West Midlands’ six million residents, one which is multimorbidity in an ageing population.

“If we are really going to tackle the issues that we are facing with our ageing population, we have to understand the biological drivers of multimorbidity with advancing age acknowledged as the major risk factor,” says Professor Janet Lord, director of the Institute of Inflammation and Ageing at the University of Birmingham.

Multimorbidity is defined as the presence of two or more conditions in an individual. Importantly, multimorbidity occurs as clusters of diseases, and whilst there are different views on what the clusters are and how many exist, Lord says that most would agree there are three main clusters:

• Cardiovascular/metabolic – including heart disease, hypertension and Type 2 diabetes
• Musculoskeletal – including arthritis and osteoporosis
• Neuropsychiatric – including mental health conditions and dementia

“Currently the medical profession and pharma industry are not addressing the issue of multimorbidity with any vigour,” she adds.  There are many reasons for this. At the moment we treat the component conditions of multimorbidity individually, which leads to multiple clinical consultations resulting in a burden on both the patient and the NHS.

“Secondly, this single-disease focus leads to polypharmacy, and we still don’t understand all of the drug-to-drug interactions that this older multimorbid patient will be experiencing and the impact on their health.

“Thirdly, our current drug development and testing programmes are also single disease focused, with many trials excluding the multimorbid patients they will most likely be prescribed to.”

Porkess adds that there are many other challenges in researching drugs that take into account multiple conditions.

“Researching a new medicine is a highly regulated process,” she says. “It is essential to be able to demonstrate to the regulator that any potential new medicine is safe and works for the condition being targeted.

“That means when you test a potential medicine in clinical trials, the traditional model is that it is tested on people who have the disease you are targeting, and only that disease.

“If there is a change to that person’s condition during the trial, you can be more confident that the potential medicine is making a difference. The presence of multiple conditions makes the evidence less clear.”

The fact that multimorbidity frequently occurs in older people adds extra challenges as it can be more difficult to recruit older people into clinical trials and harder to help them stay in the trial for the whole duration of the study.

“These are structural issues in research that can be addressed,” says Porkess, “and we are determined to think creatively, with our partners in Birmingham and others, on how to do that.”

Lord agrees that the NHS, academia and industry need to work together to have a “completely new approach” to multimorbidity.

“Instead of continuing to develop drugs for a single disease we should be looking at tackling the generic biological drivers of these multimorbidity clusters.

“As age is the single biggest risk factor for multimorbidity, an obvious starting point is to target the biological processes that underlie the ageing process itself¹. Until recently this would not have been possible, but we now understand what these processes are² and animal studies have shown that if you inhibit core ageing processes such as cell senescence you can prevent many age-related conditions including sarcopenia, cognitive decline and cardio-respiratory compromise.

“This field is moving fast and the first trials in humans were reported in 2019 showing that intermittent dosing with repurposed drugs that kill senescent cells reduced physical frailty in patients with Idiopathic Pulmonary Fibrosis³.”

She adds that this new approach would include uniting the comprehensive health data and patients in the NHS; the understanding of the biological drivers of multimorbidity clusters in academia; and the drug discovery capabilities of industry.

“We can accelerate drug discovery and clinical trials aiming to prevent or treat age-related multimorbidity and the associated polypharmacy.”

“By bringing the NHS, academia and industry together we can create a completely new approach to multimorbidity,” adds Porkess, “which could change the lives of millions of people in the UK.”

The ABPI’s Multimorbidity Action Group is open for companies and other organisations to join. Contact Su Jones (SuJones@abpi.org.uk) for more details.

References

1. Ermogenous C, Green C, Jackson TA, Ferguson M, Lord JM (2020) Treating age-related multi-morbidity: The drug discovery challenge. Drug Discovery Today. https://doi.org/10.1016/j.drudis.2020.06.016
2. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013; 153(6):1194–1217.
3. Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019; 40:554–563.