The past year in rheumatology has brought significant advances across autoimmune and inflammatory diseases. Several key additions to the literature published in this timeframe were presented during the Year in Review at ACR Convergence 2026.
Presenters William Robinson, MD, PhD, the James W. Raitt Professor at Stanford University, and Liana Fraenkel, MD, MPH, Director of Medical Education and Director of Population Health Research at Berkshire Medical Center, shared several noteworthy developments and trial outcomes. Dr. Robinson focused on basic science research, and Dr. Fraenkel discussed clinical science developments.
A recording of the session will be available to registered participants of ACR Convergence 2026 for on-demand viewing.
Basic Science
Dr. Robinson highlighted 16 studies spanning a range of rheumatic diseases, but centered around three topics: newly defined sources of neoantigens, evidence of stroma effects in rheumatoid arthritis (RA), and innate immunity and autoinflammation.
One paper on newly defined sources of neoantigens found that lupus B and T cells recognize interferon (IFN)-induced neoantigens, reframing lupus from a loss of tolerance to self toward a patient-private cryptic neoantigen response.
Another study, published in the Annals of the Rheumatic Diseases, demonstrates that stromal abnormalities precede RA. Researchers observed enhanced synovial fibroblast lipolysis and metabolic reprogramming of the stroma prior to immune-cell infiltration in the preclinical RA synovium. These findings raise the possibility of the stroma as a prevention target, rather than a lymphocyte-directed one.
“This suggests that by the time synovitis is visible on ultrasound, both the stroma and the immune cell compartment have changed in the synovium of people at risk of developing RA,” Dr. Robinson said.
Among the research demonstrating that the stroma affects outcomes in RA, he shared a paper reporting data showing that treatment-resistant RA is a stromal problem.
After performing spatial transcriptomics on paired pre- and post-treatment synovial biopsy samples from non-remitting patients, researchers observed fibrogenic signaling within perivascular niches with cartilage oligomeric matrix protein (COMP)-high fibroblasts. This indicates that the endothelial Notch ligand DLL4 induces transforming growth factor (TGF)-beta production while suppressing TGF-beta signaling, thereby creating a proximal-to-distal gradient around the vessels, Dr. Robinson noted.
“We may be treating the immune infiltrate in RA while inadvertently selecting for stroma that sustains the disease,” he said.
Another study may explain the different distribution of arthritis between joints and suggests that susceptibility to arthritis begins before birth. Researchers examined human fetal finger joints and characterized the proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP) joints. The PIP joints exhibited a larger synovial volume and were enriched for PI16-positive “universal fibroblasts.”
“The findings provide a developmental explanation for one of rheumatology’s longstanding questions: Why does RA affect the PIP joints but spare the DIP joints?” Dr. Robinson said.
Among the highlighted papers on innate immunity and autoinflammation, Dr. Robinson summarized studies identifying cell division cycle 42 (CDC42) as pyrin’s missing ligand, as well as data showing that VEXAS has two distinct mechanisms arising from a single mutation.
Dr. Robinson said that data indicate Epstein-Barr virus (EBV) infects and reprograms autoreactive B cells into driver antigen-presenting cells in systemic lupus erythematosus (SLE) and multiple sclerosis (MS). He also noted that CD19 chimeric antigen receptor (CAR) T cells appear more effective than rituximab at resetting the EBV-positive autoreactive B cell repertoire.
Clinical Science
Dr. Fraenkel, who is also Adjunct Professor at Yale University, presented several phase 3 trials, including studies evaluating sotatercept use for pulmonary artery hypertension. Several trials reported benefits with sotatercept, including improved 6-minute walk in the STELLAR trial, lower death and hospitalization rates in the ZENITH trial, and a 77% lower risk of clinical worsening. However, she noted concerns with safety and adverse events, emphasizing the need for longer follow-up.
She also presented data suggesting a benefit of retatrutide in osteoarthritis (OA), noting that while progress has been made for patients with obesity, access remains a concern due to high costs.
Dr. Fraenkel highlighted other notable trials published this year, including research on semaglutide and tirzepatide, that suggest that these may be more promising than ixekizumab alone for treating psoriatic arthritis.
“GLP-1 [glucagon-like peptide-1] receptor agonists were also associated with decreased major adverse cardiovascular events, renal progression, and mortality in lupus, although this evidence came from a lupus-emulated target trial,” Dr. Fraenkel said.
Two recent phase 3 trials of ianalumab, published together in the New England Journal of Medicine, also appear promising for the treatment of Sjogren’s disease.
“Both trials were positive, and the primary outcome reached statistical significance,” Dr. Fraenkel said. “However, the difference between the placebo and treatment groups was small and of questionable clinical significance. The primary outcome was also not supported by improvements in secondary outcomes.”
Dr. Fraenkel also shared results from a study that found a probiotic was not more effective than a placebo for patients with psoriatic arthritis across multiple outcomes at 12 weeks.
She concluded by referencing a study demonstrating impressive results for patients with OA. Patients were randomized to perform different exercises of low-, moderate-, or high-intensity levels. Researchers found a dose-response improvement in pain, functional outcomes, cartilage metabolic markers, and cartilage volume.
“We have seen many positive trials that may lead to new, effective treatments for our patients. However, more choices make decision-making more complicated,” Dr. Fraenkel said. “We now need evidence-based guidance on which medications are best for which patients—especially in lupus—and how best to sequence treatment.”
THERE’S STILL TIME TO JOIN US
If you haven’t registered for ACR Convergence 2026, you can still register on-site at the Orange County Convention Center in Orlando, Florida, through November 11. All registered participants receive on-demand access to scientific sessions through September 30, 2027.
