New data presented at the EULAR Congress 2026 suggest CAR-T therapies may deliver sustained remission across multiple refractory rheumatic and musculoskeletal diseases, with emerging evidence supporting a disease-modifying ‘reset’ of adaptive immunity.

Conventional treatment strategies for rheumatic and musculoskeletal diseases (RMDs) typically require ongoing immunosuppression to control disease activity.

Achieving durable, treatment-free remission remains challenging, particularly in patients with refractory disease, but the development of chimeric antigen receptor T (CAR-T) therapies may offer hope for patients, as presentations at the European Alliance of Associations for Rheumatology (EULAR) Congress 2026 explained.

COMPARE trial and refractory rheumatoid arthritis

The prospective, open-label COMparison of B-cell depletion by rituximab and anti-CD 19 CAR-T therapy in patients with rheumatoid arthritis (COMPARE) trial evaluated mivocabtagene autoleucel – an autologous fully human CD19-directed CAR-T cell therapy – in six patients with anti-citrullinated protein antibody (ACPA)-positive, treatment-refractory active rheumatoid arthritis.

Lead author, Dr Fredrik Albach, resident doctor in the Department of Rheumatology and Clinical Immunology at Charité – University Medicine Berlin, presented Phase 1 data, describing how mivocabtagene autoleucel treatment was generally well tolerated.

Cytokine release syndrome (CRS) was limited to mild-to-moderate events, while no immune effector cell-associated neurotoxicity syndrome (ICANS) or unexpected toxicities were reported.

CAR-T cells expanded rapidly, reaching peak levels within three weeks before gradually declining.

The investigators observed effective B-cell depletion in blood and tissues, with a median reduction in autoantibody levels of more than 90%. Sustained seroconversion to normal ACPA levels was achieved in four patients, and five achieved normal rheumatoid factor immunoglobulin (Ig) M levels.

Disease activity also improved, with a median 49% reduction in the Disease Activity Score 28. American College of Rheumatology (ACR) 20, ACR50 and ACR70 responses were recorded in five, four and two patients, respectively.

Importantly, half of the participants achieved sustained remission without ongoing immunosuppressive therapy. During B-cell repopulation, re-emergence of ACPA-positive memory B cells, rising autoantibody levels and increased disease activity were not observed.

At data cut-off, all but one patient remained off immunosuppressive treatment after 24–36 weeks of follow-up.

Reference: Albach FN et al. CD19 CAR T-Cell Therapy in ACPA-Positive, Treatment-Refractory, Active Rheumatoid Arthritis – Data from the Phase 1 of the Prospective, Interventional COMPARE Trial. Presented at EULAR 2026; OP008. Ann Rheum Dis 2026; doi: 10.1136/annrheumdis-2026-eular.B.2103.

Dual-target CAR-T in systemic sclerosis

A separate multicentre study assessed dual-target CD19/BCMA CAR-T therapy in 11 patients with refractory systemic sclerosis (SSc).

Functional disability improved substantially, with Health Assessment Questionnaire Disability Index (HAQ-DI) scores falling from 1.0 to 0.2. Physician and patient global assessments also improved.

Beyond skin involvement, investigators reported stabilisation or improvement in lung function, including measures of lung volume and oxygen transfer.

Among the five patients with baseline interstitial lung disease, forced vital capacity and diffusing capacity for carbon monoxide stabilised or improved, with a median increase of 8% predicted.

High-resolution computed tomography demonstrated regression of interstitial lung disease changes in 80% of patients with baseline pulmonary involvement.

No disease flares were reported during follow-up. One patient with overlap syndrome required retreatment but subsequently achieved remission following a second infusion.

Presenting the findings, Dr Yajing Zhang, executive director of the Myeloma and Lymphoma Department at Beijing GoBroad Boren Hospital in China, said: ‘Dual-target CD19/BCMA CAR-T cell therapy induces profound and sustained clinical remission in refractory systemic sclerosis.

‘By effectively targeting both skin fibrosis and lung progression, this immunological ‘reset’ strategy offers true curative potential, paving the way for Phase 2 trials to redefine the future management of this severe disease’.

Reference: Cheng F et al. Clinical Efficacy Angle – Sustained Remission in Refractory Systemic Sclerosis with Dual-Target CAR-T Therapy. Presented at EULAR 2026; OP0311. Ann Rheum Dis 2026; doi: 10.1136/annrheumdis-2026-eular.B.4629.

Microbiome findings offer insight into immune recovery

Additional research explored how CD19-directed CAR-T therapy influences the gut microbiome and mucosal immunity in patients with severe systemic lupus erythematosus (SLE), SSc or idiopathic inflammatory myopathy.

The study included 20 patients with autoimmune disease – nine with SLE, eight with SSc and three with idiopathic inflammatory myopathy – who received a single infusion of autologous CD19 CAR-T cells.

Gut microbiota composition and faecal Ig A levels were assessed before treatment and six months afterwards, alongside comparisons with 23 age- and sex-matched healthy controls.

Dr Yuichi Maeda, group leader and researcher at the Friedrich-Alexander University of Erlangen–Nuremberg and University Hospital Erlangen, Germany, detailed how microbial diversity before treatment was reduced compared with healthy controls and remained lower six months after therapy.

However, enrichment of Streptococcus species observed at baseline decreased to levels comparable with healthy controls following treatment, he said. Faecal IgA concentrations also fell significantly, indicating reduced mucosal immune activity.

Patients with delayed CD19-positive B-cell reconstitution had significantly lower baseline faecal IgA levels, suggesting mucosal immune status may influence immune recovery after CAR-T therapy.

Anti-commensal IgA and IgG levels were also significantly reduced six months after treatment, indicating sustained attenuation of humoral responses directed against intestinal bacteria.

The authors concluded that these immunomicrobial changes may contribute to long-term disease remission and could help to identify factors influencing immune reconstitution following CAR-T therapy.

Reference: Maeda Y et al. Immune Reset and Microbial Shifts: Gut Microbiota Dynamics After CD19 CAR T-Cell Therapy in Autoimmune Disease. Presented at EULAR 2026; OP0152. Ann Rheum Dis 2026; doi: 10.1136/annrheumdis-2026-eular.A.343.

Novel E-CAR-T construct and improved safety

A poster from Dr Xiaobing Wang, lead researcher and physician at the National Key Laboratory for Immunity and Inflammation, Shanghai Changzheng Hospital in China, detailed first-in-human data on a novel E-CAR-T construct designed to address the limitations of conventional second-generation CARs.

Conventional CAR-T constructs that rely on CD28 or 4-1BBζ signalling can induce supraphysiological T-cell activation, which has been associated with CRS and ICANS toxicities.

Unlike these CD28- or 4-1BBζ-based constructs, E-CAR-T incorporates the CD3ε cytoplasmic domain to optimise signalling while reducing tonic activation. According to the investigators, this approach aims to improve signal transduction by recruiting physiological negative regulators of T-cell activation, thereby reducing excessive signalling.

In a pilot study involving four patients with SLE or SSc, the therapy demonstrated deep tissue-level remission alongside what investigators described as a superior safety profile compared with conventional CAR-T approaches.

The researchers also observed differentiation into a tissue-resident memory phenotype, which may represent a mechanism for maintaining disease control despite peripheral CAR-T cell clearance.

Reference: Wang X et al. First-in-Human Autologous Anti-CD19 E-CAR-T Therapy with a Novel CD3ε Domain Induces Deep Tissue Remission and Resident Memory Differentiation in Refractory Autoimmune Diseases. Presented at EULAR 2026; POS0374. Ann Rheum Dis 2026; doi: 10.1136/annrheumdis-2026-eular.B.1728.

What might this mean for RMD clinical practice and CAR-T?

Although based on small, early-phase studies, these findings presented at EULAR 2026 provide further evidence that CAR-T cell therapies may offer more than temporary disease suppression in selected patients with refractory RMDs.

Across multiple disease settings, investigators reported durable clinical responses, sustained reductions in autoantibodies and evidence consistent with an immunological reset.

Larger studies will be needed to confirm long-term efficacy, safety and patient selection strategies, but the field appears to be rapidly advancing towards a potential new therapeutic paradigm in autoimmune disease.