Ozempic will change rheumatology Save

Ozempic is everywhere. Even all the way in Australia, where we have highly constrained supply that makes headlines and substantial limits on direct-to-consumer advertising, somehow I know the jingle from the American ad for Ozempic. I have no special interest or personal gain to be made, but so pervasive is its cultural significance that its ubiquitous brand recognition should come as no surprise.

Our rheumatology patients are no different. They live in a broader world where we are far from the sole influence on their healthcare knowledge or decision making. We can choose to ignore it, promote it, or something in between, but our patients will be the ones who actively raise the subject, whether we like it or not.

With so many of our diseases made worse by obesity, notably rheumatoid arthritis, psoriatic arthritis, and osteoarthritis, there is plausible gain from this. Much of the refractory pain and suffering from these conditions might be attributable to obesity, so active questions will be raised about how GLP-1 agonists can influence the diseases we treat.

A preview of that impact came on this year’s ACR Convergence poster floor, with a cohort of 152 rheumatoid arthritis patients from Los Angeles (perhaps the home of the Ozempic trend) captured by colleagues from UCLA (abstract 2259). In this, they looked at longitudinal changes in RA metrics for patients taking either semaglutide or tirzepatide, currently the two main GLP-1 agonists used for weight loss. Notably, these patients not only recorded weight loss and improvements in HbA1c, but also saw improvements in pain and acute phase reactants.

Additionally, a further oral abstract from the FORWARD group addressed patients taking any weight loss medicine, and showed that achieving >5% weight loss was associated with improved pain and function in overweight patients (abstract 0845). While this has been elusive to achieve in the past, GLP-1 agonists have far greater success, albeit with provisos around cost and duration of therapy.

In a world where pain and disease activity is often incompletely managed in obese rheumatology patients, and readily actionable therapies have been hard to implement in the past, it is entirely possible that we will be the ones initiating the conversation. Whether we should or not will, of course, be predicated on many things, including whether we generate sufficiently high quality data to warrant this becoming a priority.

The start of this might be in knee osteoarthritis, where obesity has long been identified as a key factor, effective pharmacotherapeutic approaches are lacking, and the size of the potential market still remains larger than either RA or PsA. A recent double-blind RCT of semaglutide versus placebo, published in the New England Journal of Medicine last month, showed meaningful gains in pain and function. (https://www.nejm.org/doi/full/10.1056/NEJMoa2403664) This will no doubt become a therapeutic focus, and for patients with access, it might be one of the key interventions leading to benefit.

We are yet to see such data for rheumatoid arthritis and psoriatic arthritis, and high quality data is surely needed to inform our decision making.

Even with such data, many issues will still arise, of course. Apart from neglect of still-effective non-pharmacological approaches, access to GLP-1 agonist therapy will remain a large question, particularly given existing costs and globally constrained supply. A poster from osteoarthritis experts looking at health economic modelling suggests that, in certain situations over a five year horizon, a GLP-1 agonist intervention could make pharmacoeconomic sense in knee osteoarthritis (abstract 1050).

Whether this will resonate with insurers and other payers remains to be seen - but equally, patients in whom it does not necessarily make sense might gain access too, for better or for worse. There are incompletely answered questions about the long-term game plan for such patients - will they need indefinite treatment to sustain benefit, and will that be justifiable? And will such therapy be tolerable?

Only time will tell how GLP-1 agonist strategy will be implemented for rheumatology patients. What is for sure, however, is that rheumatology will not be able to close its eyes to the impact of Ozempic.