CAR-T cell therapy induced sustained, drug-free remission across multiple severe autoimmune rheumatic diseases, according to three early-phase studies presented at EULAR 2026 in London, adding weight to the concept of immune “reset” as a treatment strategy.
The results spanned refractory rheumatoid arthritis, systemic sclerosis and connective tissue diseases, with consistent signals of deep B-cell depletion, falling autoantibody levels and clinical improvement.
RA: remission without immunosuppression
In a late-breaking session, Dr Fredrik Albach from Universitätsmedizin Berlin reported phase 1 results from the COMPARE trial, which evaluated the autologous CD19-directed CAR-T therapy mivocabtagene autoleucel in six patients with ACPA-positive, treatment-refractory RA.
The safety profile was reassuring: cytokine release syndrome was limited to mild-to-moderate events, with no ICANS or unexpected toxicities. CAR-T cells expanded rapidly after infusion, peaking within three weeks, while B cells were depleted in both blood and tissue.
Autoantibody reductions were marked:
- Median decreases exceeded 90%
- Four patients achieved sustained seroconversion to normal ACPA levels
- Five achieved normalisation of rheumatoid factor IgM levels
Disease activity fell substantially, with a median 49% reduction in DAS28-CRP. ACR20, ACR50 and ACR70 responses were achieved by five, four and two patients respectively. Three patients achieved sustained remission without ongoing immunosuppressive therapy, and at 24 to 36 weeks, all but one remained off immunosuppression.
Mechanistically, treatment produced deep remodelling of the autoreactive B-cell compartment, with depletion of CD19 B cells and plasmablasts and predominantly naive B-cell repopulation.
“A single infusion induced clinical improvement despite complete discontinuation of conventional immunosuppression, supporting the concept of a time-limited intervention with potential for drug-free remission,” Dr Albach told the congress.
Systemic sclerosis: skin and lung benefits
Chinese researchers reported the first multicentre experience of dual-target CD19/BCMA CAR-T therapy in 11 patients with refractory systemic sclerosis.
All patients achieved rapid B-cell aplasia. Skin thickness scores improved significantly, 73% reached low disease activity, and functional disability measured by HAQ-DI fell from 1.0 to 0.2. Physician and patient global assessments also improved.
Patients with interstitial lung disease also benefited: lung volume and gas transfer stabilised or improved, and high-resolution CT showed regression of interstitial changes in 80% of affected patients. No disease flares occurred during follow-up. One patient with overlap syndrome required retreatment and achieved remission after a second infusion.
Yajing Zhang from Beijing GoBroad Boren Hospital said the findings showed dual-target CD19/BCMA CAR-T therapy could induce profound and sustained clinical remission in refractory systemic sclerosis, with potential to address both skin fibrosis and lung progression.
Gut microbiome: a window on immune recovery
A third study examined the effects of CD19-directed CAR-T therapy on the gut microbiome and mucosal immunity in patients with severe SLE, systemic sclerosis and idiopathic inflammatory myopathy treated with zorpocabtagene autoleucel.
Before treatment, patients showed markedly reduced gut microbial diversity compared with healthy controls. An overgrowth of Streptococcus species fell to levels comparable with healthy controls after treatment. Faecal IgA levels also fell significantly, indicating reduced mucosal immune activity.
Patients who experienced delayed B-cell reconstitution had significantly lower baseline faecal IgA levels, suggesting mucosal IgA status at baseline may predict immune recovery after CAR-T therapy.
Dr Yuichi Maeda from Suita, Japan, concluded that these immunomicrobial shifts may support long-term disease remission, and that mucosal immune status could be a key regulator of immune recovery after CAR-T cell therapy.