A must-see at ACR Convergence, here is a selection of the best papers published over the last year – complete with links.
The Clinical Year in Review was presented at ACR 2023 by Associate Professor Philip Seo of Johns Hopkins University, and covers papers published since the end of last year.
Dr Seo began with an “update of last year’s update” featuring two follow-ups to papers from the same session at the last conference.
The first was the ORAL investigator study on tofacitinib in rheumatoid arthritis.
In this year’s update, the ORAL investigators combined their data with studies from two other studies of RA and inflammatory bowel disease, giving them six years of follow up data.
“And they came up with a really interesting analysis,” said Dr Seo.
“They were able to demonstrate that if you looked only at patients who are younger than 65, and did not have a history of smoking, that there didn’t seem to be an increased risk of these adverse events. And it’s possible that they managed to highlight a group of patients who can use tofacitinib and other JAK inhibitors relatively safely.”
The second paper revisited from last year was the GLORIA trial, which looked at patients older than 65 to examine the effect of adding low-dose glucocorticoids to a stable regimen.
In the study that they published this past year, they did a follow up where participants were tapered off relatively quickly over a period of three months.
“I think interestingly, no one developed adrenal insufficiency and I say that’s interesting because I think that clinically that’s the thing that most of us would have been concerned about, but they did not see evidence of this.
“Less surprisingly, they found that if you taper off the glucocorticoids, there’s a small increase in disease activity.
“If you have low level disease activity, [tapering] is probably not the best strategy, because taking you off that last little bit of steroids might induce a disease flare.”
Dr Seo then turned to recent studies published in the Lancet Rheumatology looking at global burden of disease in rheumatological conditions.
The study on osteoarthritis showed a 132% increase in the prevalence of osteoarthritis from 1990 to 2020. A look at “other musculoskeletal disorders”, a broad category that includes conditions such as lupus and spondyloarthritis, found an increase of 123% from 1990 to 2020, with an estimated 494 million people affected globally. That in turn is expected to increase by 50% by 2050.
“So for those of you who are planning on an early retirement, you may need to make other plans.”
Dr Seo then turned his attention to “new-ish” diseases, including a case series on DOCK11 deficiency and a paper on the estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome.
Dr Seo suggested that rare diseases were more common that we realise, and said he was “haunted as a clinician” by the words of Professor Seza Ozen, president-elect of the Paediatric Rheumatology European Society: “What you think of as a rare manifestation of a common disease is probably a common presentation of a disease you are not aware of (yet).”
Moving onto rheumatoid arthritis, Dr Seo highlighted the NORD-STAR trial, which not only tested “the patient populations you would want to look at” – people with early active, moderate to severe RA who’d not been treated previously – but also compared several treatment regimens “that you might actually use”.
They found that triple therapy was the worst option, certolizumab and abatacept were significantly better, and tocilizumab belongs in a second-place category.
“I think that NORD-STAR really highlights that maybe abatacept belongs a little bit higher in the hierarchy of drugs that we consider when we’re looking at a patient with new rheumatoid arthritis.”
In osteoarthritis, data from the LoDoCo2 study looking at low-dose colchicine in patients with stable coronary artery disease was examined for association of low-dose colchicine with incidence of knee and hip replacements. The risk of knee and hip replacement was lower in patients randomised to low-dose colchicine, which “certainly raises some intriguing opportunities”.
Then to some new drugs coming down the pipeline.
PD-1 stimulator peresolimab demonstrated a response in RA patients that had failed other treatments, including biologics, but perhaps more significantly highlighted a new pathway apparently important to the pathogenesis of RA.
ABBV-3373 is a hybrid molecule combining adalimumab plus a glucocorticoid receptor modulator, and when compared to adalimumab alone was able to demonstrate a substantial response in joint disease. There was also a suggestion of prolonged benefit in patients with low disease activity who discontinued the drug.
“And I think this is especially exciting when you think about diseases like lupus and vasculitis that are often treated with very high doses of glucocorticoids, because this may represent a path forward for them.”
Brepocitinib in psoriatic arthritis had a substantial response in both joint disease and skin disease, which was maintained for 52 weeks’ follow up. It’s also being looked at as a treatment for lupus and dermatomyositis.
Meanwhile the BE OPTIMAL and BE COMPLETE bimekizumab studies showed improvements in skin and joint disease in PsA.
The TYK2 inhibitor deucravacitinib was trialled at various doses for lupus and there was a significant response in terms of the primary endpoint, SRI-4. Interestingly, there was a lesser response with the higher doses, and Dr Seo suggested there may be some kind of compensatory mechanism that kicked in at higher doses that inhibits therapeutic response. However, he acknowledged that it may be a statistical anomaly and more data was needed.
The soluble guanylate cyclase stimulator riociguat has anti-proliferative and anti-fibrotic properties, suggesting it would be good therapy for scleroderma – but unfortunately in the initial study, this wasn’t the case. However, a long-term extension study suggested that in the right patients it may be effective for the prevention of digital alterations.
After a brief moment of silence for the cessation of baricitinib development in SLE, Dr Seo moved onto a case report looking at TRBV9+ CD8+ T cells which have been implicated in the pathogenesis of ankylosing spondylitis. An antibody developed to deplete these cells successfully treated a man with long-term ankylosing spondylitis, and he has been in remission for four years.
“This is an incredible result and it’s already in phase two investigation. So we’ll look forward to additional data in the near future.”
Dr Seo included the SAPHYR study of sarilumab in polymyalgia rheumatica among his top papers of 2023. Patients were randomised to receive sarilumab plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Around 28% of the sarilumab group achieved sustained remission, compared with around 10% of controls, and there was a substantial reduction in cumulative glucocorticoids.
A long-term outcome study of rituximab as maintenance therapy for ANCA-associated vasculitis suggested that “the majority of the benefit that patients with ANCA-associated vasculitis receive from rituximab really occurs during the first few years of therapy.
“And it’s quite possible the majority of patients do not require long term therapy in terms of the years and years that we currently see.”
The excitement surrounding CAR T-cell therapy in rheumatic conditions may be premature, suggests Dr Seo, who presented two case reports indicating things may be more complicated than they seem.
The first was a 41-year-old man with Jo-1 positive myositis who responded beautifully to the therapy – for a week. He then developed cytokine storm and developed recurrent muscle disease requiring treatment with MMF.
Another patient with severe systemic sclerosis was treated with CD19-targeted CAR T cells and did experience some clinical benefit.
“The problem with this report is that the patient did not improve in the domains that we would care about. So the patient did not have improvement in pulmonary fibrosis and did not have an improvement in left ventricular ejection fraction.
“I don’t think this study means that CAR T-cell therapy does not have a role in the treatment of patients with scleroderma. But it does highlight the importance of selecting the right patients for these interventions in the future.“
Not wishing to leave us on that gloomy note, Dr Seo finished his clinical year in review with a study on the benefits of pizza for rheumatoid arthritis. But, he emphasised, it has to be proper Italian pizza.
“I like this study because it highlights that sometimes good news comes from where you least expect it.”
