Joint Ventures: CAR-T, Early Diagnosis Reshape Scleroderma at EULAR 2026

The therapeutic framework for systemic sclerosis is undergoing a fundamental reorientation, moving away from managing visible fibrotic sequelae toward targeting the autoantibody-driven mechanisms believed to initiate and propagate disease.

On a recent episode of Joint Ventures recorded live at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress in London, host Jack Arnold, MBBS, PhD, of the University of Leeds, spoke with Vishal Kakkar, MD, also of the University of Leeds and a specialist in scleroderma, about the most consequential data emerging from the congress.

Dual CAR-T Targeting of CD19 and BCMA

Emerging evidence presented at the congress supports reconceptualizing systemic sclerosis as an autoantibody-driven condition rather than primarily a fibrotic disease. Data on antitopoisomerase I and anti-RNA polymerase III antibodies indicate these markers may actively drive disease through mitochondrial damage and cellular entry, rather than simply reflecting it.

Building on prior work with rituximab in scleroderma, including an Italian group demonstrating superior skin and lung outcomes with rituximab plus mycophenolate mofetil over either agent alone, a Chinese group led by Zhang presented a proof-of-concept study evaluating CAR-T therapy with dual targeting of CD19 and B-cell maturation antigen (BCMA). The nine-patient study demonstrated what investigators termed immunological reset, with reductions in antitopoisomerase I antibodies observed alongside the broader B-cell depletion.

The same group presented a companion abstract optimizing CAR-T delivery in scleroderma's fibrotic tissue environment, using EDTA chelation to improve cellular access and efficacy. The rationale is clinically important: unlike lupus, the fibrotic milieu in scleroderma presents an additional barrier for cell-based therapies, and standard CD19-only CAR-T approaches leave long-lived plasma cells untouched.

Very Early Diagnosis and Pre-Clinical Disease Stratification

Alongside cellular therapy advances, EULAR 2026 featured a substantial expansion of work on very early diagnosis of systemic sclerosis (VEDOSS). An Italian study conducted in collaboration with the University of Leeds identified three distinct disease subsets within the VEDOSS population, each with different progression trajectories. In one subset characterized by elevated antitopoisomerase I antibodies, nearly 50% of patients progressed to established systemic sclerosis.

A separate abstract by Thornton et al demonstrated lung ultrasound findings in VEDOSS patients distinct from those seen in established scleroderma-associated interstitial lung disease, opening new avenues for pre-clinical monitoring. Survey data also presented at the congress found clinician awareness of VEDOSS reached 84%, but gaps remain in applying the five key red flags: puffy fingers, nailfold capillaroscopy changes, SSc-specific antibodies, antinuclear antibody positivity, and Raynaud's phenomenon.

The practical takeaway for general rheumatologists is acting on those red flags when they cluster: ordering lung function testing and echocardiography early, tracking serial decline even when values remain within normal limits, and scheduling structured follow-up rather than waiting for overt organ involvement.

Collectively, the data from EULAR 2026 trace a coherent trajectory for systemic sclerosis: identifying and treating at-risk patients before fibrosis is established, and disrupting disease-driving autoimmunity with increasingly precise cellular therapies once disease is present.

Arnold’s disclosures include Alumis, Roche, and Novartis. Kakkar has no disclosures to report.