Rheumatologists showcase 2021’s key research at ACR Convergence   

One of the most popular sessions at the 2021 ACR Convergence meeting this weekend has been the Year in Review session, in which leading rheumatologists showcased key studies and developments and their important clinical implications.

Dr Karen Costenbader

In her overview of “fantastic studies in rheumatology research” in the last year, Dr Karen Costenbader, Rheumatologist at Brigham and Women’s Hospital Professor of Medicine, Harvard Medical School, spoke of “a new dawn” for the treatment of rheumatic diseases.

She highlighted US approval of two key new oral agents as add-on therapies: avacopan, an oral c5a inhibitor for ANCA vasculitis, and voclosporin, a new calcineurin inhibitor for lupus nephritis.

Avacopan’s approval followed results of an international, 143-centre, randomised clinical trial (RCT) involving 331 subjects with ANCA vasculitis, which showed that remission at 26 weeks was 72.3% for the avacopan group versus 70.1% versus prednisone arm. Also, there was no difference in serious adverse events between the two arms, and just 10% of avacopan-treated patients versus 21% of those taking prednisone relapsed within 12 months.

The efficacy and safety of voclosporin versus placebo for lupus nephritis was established in the 142-centre, 357-patient AURORA 1 trial. In this “overwhelmingly positive” study, 41% in the voclosporin group versus 23% in the placebo arm showed a complete renal response at 52 weeks. The drug also controlled proteinuria very quickly, with a 50% reduction in using PCR achieved in 29 days, without high side effects, Dr Costenbader told delegates.

Evolving story of JAK inhibitors

In other developments, 2021 saw the first trial of tofacitinib for the treatment of ankylosing spondylitis (AS). This was an international, multicentre, Phase III RCT in which 269 patients with active AS who had had an inadequate response or intolerance to two NSAIDS or more, were randomised to receive either tofactinib twice daily or placebo.

The primary outcome was the Assessment of SpondyloArthritis international Society 20 (ASAS 20) improvement at week 16, and results showed “very impressive margins”, with 56.4% for tofactinib versus 29.4% for placebo, and 40.6% and 12.5%, respectively, for ASAS 40.

However, the drug’s safety has recently been in the spotlight based on findings of a post-marketing trial for tofacitinib versus anti-TNF in rheumatoid arthritis, which led to new black box warnings for all JAK inhibitors on increased risk of serious cardiovascular events, cancer, blood clots and deaths, as previously reported by the limbic.

Improving clinical care

Dr Costenbader also highlighted studies focused on improving the clinical care of rheumatic disease patients. For example, addressing how to treat rheumatic patients with stable disease in remission, the ARCTIC-Rewind trial involved 160 subjects who were randomised to receive either a half dose of their conventional, synthetic DMARD, or a full dose.

The study found that there were significantly more flares over 12 months in the reduced dose arm, with a hazard ratio of 4.0. Therefore reducing DMARD dose was found to be the inferior treatment strategy, and this was reflected in the new 2021 ACR treatment guidelines, which conditionally recommended continuing the same dose of DMARD versus reducing in patients who’ve had stable and RA in remission for at least six months.

Another study (TICOSPA) looked at tight-control and treat-to-target strategy in axial spondyloarthritis. 160 subjects at 18 centres in Europe were randomised by site to treat-to-target strategy (four weekly visits and target AS disease activity score of less than 2.1) versus usual care.

The trial failed to reach its primary outcome of an improvement of 30% of more on the ASAS-Health Index score at 48 weeks (47% versus 36%), but many secondary outcomes on safety and cost-effectiveness were met, such as the ASAS 40 (52% versus 35%) and low disease activity score status at 48 weeks (77% versus 60%). The researchers also showed that treat-to-target added 0.4 quality adjusted life years and was cost effective, saving 472 Euros (A$737) versus usual care.

COVID-19 and rheumatology

As COVID-19 took centre stage again in 2020/2021, the studies from rheumatologists and rheumatology researchers “really contributed to our understanding of how this disease affects our patients”, Dr Costenbader said.

For example, observational data showed that in people with rheumatic diseases a higher risk of death was linked to glucocorticoid doses of more than 10 mg/day, moderate/high rheumatic disease activity and multiple immunosuppressant medications. Also, research showed that individuals on immunosuppression had reduced immunogenicity following mRNA vaccines against SARS-CoV-2 infection.

Meanwhile, in the pipeline

Dr Michael Brenner

For the basic science section of the session, Dr Michael Brenner, E.F. Brigham Professor of Medicine at Harvard Medical School and Director of the Human Immunology Center and the Single Cell Genomics Core at Brigham and Women’s Hospital in the US, described how new technologies could drive the next generation of therapies for rheumatic disease.

For example, mRNA vaccines against COVID-19 could mark the beginning of a new wave of engineered RNA and genomic therapeutic agents, he said. This mRNA technology could potentially be used for immune stimulation or tolerisation, which could “reopen efforts in antigen-specific immunotherapy,” and “has immense application to autoimmune, allergic, and transplantation conditions.”

Among others highlighted as showing early promise was a bioartificial organoid that secretes IL-1 receptor agonist (IL-1Ra) to treat serum transfer arthritis in mice, which significantly reduced pain scored and nearly eliminated bone damage in induced arthritis.

The limbic will be providing more coverage of ACR Convergence 2021 in the next issue.

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