CAR-T cell therapy for treatment-refractory rheumatic autoimmune diseases: a systematic review of clinical outcomes and safety profiles.
Level 4 - case-series / case-control
Systematic review of non-randomized studies and case series
PubMed 41781158 · doi:10.1136/rmdopen-2025-006417
What was done
This systematic review followed PRISMA guidelines (PROSPERO: CRD42025641602) and searched five databases from inception to February 2025 for primary studies investigating CAR-T cell therapy in autoimmune rheumatic diseases. Quality and risk of bias were assessed using Joanna Briggs Institute tools and the ROBINS-I tool.
What was found
Twelve studies encompassing 44 patients with treatment-refractory disease across six rheumatic conditions (median 5 prior therapies) were analyzed. CD19-targeted constructs were evaluated in 83% of studies and dual-target approaches in 17%. All studies (100%) reported clinical responses, with individual study response rates ranging from 92% to 100% and complete responses achieved within 2–16 weeks. Drug-free remissions lasted 6–46 months alongside 80%–99% reductions in disease-specific autoantibodies. Cytokine release syndrome was restricted to grades 1–2 (no grade ≥3 events), and immune effector cell-associated neurotoxicity occurred in 25% of studies, predominantly grade 1.
Why it matters
This synthesis indicates that CAR-T cell therapy can induce deep, drug-free remissions in treatment-refractory rheumatic diseases with a substantially milder toxicity profile than typically observed in oncology.
Limits
The evidence base is limited by a very small aggregate sample size (44 patients across 12 studies) derived exclusively from uncontrolled case series and early-phase non-randomized designs, carrying high risks of selection and publication bias. Long-term safety and durability beyond 46 months remain uncharacterized.
Cited by
- supports CD19-targeted CAR-T cell therapy that depletes B cells has produced sustained remissions of severe autoimmune diseases like systemic lupus erythematosus and systemic sclerosis for over three years of follow-up.