As the ACR conference kicks off, we speak to our Australian experts about the most interesting research of the day.
The American College of Rheumatology Convergence has launched in San Diego, and we’re joined by Queensland rheumatologist Professor Peter Nash to discuss the highlights of the day.Â
Delegates heard about controversies in osteoporosis, lupus prevention and the risks of telehealth, but two topics stood out to Professor Nash, from the school of medicine and dentistry at Griffith University.
One of the most interesting studies I saw today was similar to a paper we saw at EULAR in Milan on the use of semaglutide, the obesity drug, in patients with type two diabetes.
In these lupus patients, the authors showed you can reduce the risk of developing acute kidney injury, chronic kidney disease, stage renal disease, hospitalisation and heart failure.
This follows the very large Canadian study of 10,000 patients with diabetes and autoimmune disease presented in Milan, which also showed reductions in death, heart attacks and strokes.
So I think the moral of the story is that we’re going to have to start learning about these new group of drugs, the SGLT2 inhibitors and DPP4 inhibitors, because a lot of our patients are on steroids and they’ve got diabetes. We’re going to have to start using them in our obese patients, because they reduce bad outcomes.
But my favourite topic at the conference was on CAR T-cell therapy. Researchers presented a follow-up on a dozen or so German patients with serious autoimmune diseases who they treated with CAR T-cell therapy. The lupus patients had very severe disease, including renal involvement and a number of organs involved, multiple treatments had failed, they were living on unacceptable doses of prednisone – and now most are in one-to-two-year drug-free remission following this CAR T therapy.
The presenters also showed a couple of cases of myositis, similarly in drug free remission over a 12-month period, and a couple of cases of scleroderma who have also done very well with CAR T-cell therapy.
Now the local Queensland Institute of Medical Research say they can do CAR T-cell therapy for around $75,000. If it was your daughter getting renal damage, living on steroids, living on immune suppression, and you could offer her this treatment and she’d be completely drug free and in remission for two years, you’d probably jump at the chance.
But right now, there are all these places around the world just doing little tiny case series observational studies, and it really is about time they did a proper trial.
We need a study that answers the question: do you need the induction therapy with fludarabine and cyclophosphamide?
Because currently they take the person’s T-cells, they infect them with a lentivirus that makes them express the CD19 CAR, and then they infuse it back in the patient. After the patient has stopped all their immune-suppressing drugs, and after they’ve been induced with this oncology regimen of cyclophosphamide and fludarabine, then the B cells come back in an average of 50 to 150 days later – and they’re not autoreactive anymore and they stay in remission. All the autoantibodies go away and complements normalise, they’re off all their drugs and they’re in remission for extended periods of time.
Safety data on these patients showed that apart from some upper respiratory tract infections – because these particular patients were treated through the covid pandemic – they don’t get myelotoxicity, they get very mild grade I cytokine release syndrome, a couple of them had to have tocilizumab as treatment, and they don’t seem to get the neurotoxicity seen in oncology trials.
The lack of cytokine release syndrome may be because the actual bulk of B cells that they’re knocking off is really quite small in volume, whereas the lymphomas have a huge amount of disease that they have to knock off.
It’s also possible that the lack of neurotoxicity is because there are not a lot of lymphoma B cells in the central nervous system that they’re knocking off that might cause local problems.
The researchers even showed that because most plasma cells don’t express CD19 they get left alone, and patients respond normally to vaccination as far as making antibodies is concerned.
So the safety seems to hold up quite nicely.
The efficacy is certainly very, very impressive.
But the therapy is expensive, and they need to do some controlled studies now. The ideal trial would be CAR T-cell treatment on one side, knocking off CD19-carrying B cells, and on the other side would be a monoclonal antibody, like obexelimab, which is a CD19 monoclonal a little bit like rituximab.
So those are a couple of things that I found really interesting: that we should be using the semaglutide in our obese and especially our diabetics patients with autoimmune disease because it’ll save lives and heart attacks. And we should be investigating CAR T-cell therapy further and defining who’s the right patient for it and what’s the regimen that you need to get a good result.
This interview has been edited for length and clarity.
