Chimeric antigen receptor-based cellular therapy in autoimmune diseases: A systematic review and meta-analysis of clinical, serological and safety outcomes.

OBJECTIVE

Chimeric antigen receptor (CAR)-T cell and natural killer cell therapies are emerging as treatments for autoimmune diseases (AIDs), capable of inducing immune reprogramming and drug-free remission. However, their efficacy, safety, and durability across AIDs remain incompletely defined.

METHODS

We performed a systematic review and meta-analysis of proportions to evaluate the efficacy and safety of CAR-based therapies in AIDs. PubMed, Embase, and CENTRAL were searched from January 1, 2010, to October 20, 2025. The primary outcome was medication-free remission (MFR); secondary outcomes included disease-specific remission indices, incidence of adverse events and their severity. Subgroup and meta-regression analyses were conducted.

RESULTS

Of 3367 records screened, 56 studies met the inclusion criteria (15 eligible for meta-analysis; 41 synthesized qualitatively). For CAR-T cell therapies, among SLE patients, pooled MFR was 0·76 and DORIS remission 0·75. Subgroup analyses revealed a longer disease duration was associated with lower remission rates. From the qualitative analysis, CAR-T cell therapies demonstrated promising clinical efficacy and seroconversion rates in other AIDs, such as systemic sclerosis, myositis and myasthenia gravis. Across all AIDs, CRS of any grade occurred in 0·63, but grade ≥ 3 CRS and any grade of ICANS were negligible (both 0·00). Hypogammaglobulinaemia of any grade occurred in 0·47, while grade ≥ 3 events were rare. Cytopenias were common: neutropenia and anemia of any grade were most frequent. Severe cytopenias occurred in ≤0·3. Infection within 3 months occurred in 0·29.

CONCLUSION

CAR-T cell therapies targeting CD19 or BCMA appear highly effective in inducing remission in refractory autoimmune diseases, with predominantly mild CRS and negligible neurotoxicity.