LONDON — Fredrik Albach presented Phase 1 results from the COMPARE trial showing that mivocabtagene autoleucel, an autologous, fully human CD19-directed CAR-T cell therapy, induced sustained remission in half of six patients with treatment-refractory rheumatoid arthritis at the 2026 Congress of EULAR in London. The trial enrolled patients with anti-citrullinated protein antibody (ACPA)-positive, active disease who had not responded to conventional therapies.

The CAR-T treatment was generally well tolerated, with cytokine release syndrome limited to mild-to-moderate events and no cases of immune effector cell-associated neurotoxicity syndrome or unexpected toxicities reported. CAR-T cells expanded rapidly, peaking within three weeks before gradually declining. B cells were effectively depleted in both blood and tissues following treatment.

Autoantibody levels dropped substantially, with a median reduction exceeding 90%. Sustained seroconversion to normal ACPA levels occurred in four patients, and five achieved seroconversion for RF-IgM. All six participants showed reduced disease activity, marked by a median 49% reduction in DAS28-CRP scores. Five of six met ACR20 response criteria, four met ACR50, and two achieved ACR70 responses.

Three of the six patients achieved sustained remission without ongoing immunosuppressive therapy. With the exception of one patient who resumed glucocorticoids due to a moderate flare after withdrawal, all participants remained off immunosuppressive drugs at data cutoff, with follow-up ranging from 24 to 36 weeks. When B cells repopulated, there was no return of ACPA-positive memory B cells, no rise in autoantibodies, and no increase in disease activity.

Current rheumatoid arthritis therapies typically require continuous immunosuppression, and remission without drug treatment remains uncommon. Recent anecdotal evidence has suggested CD19-directed CAR-T therapy might offer a new approach. The COMPARE findings support the concept of an immunological reset in rheumatic diseases, potentially enabling durable remission without long-term immunosuppression.

The COMPARE trial is a prospective, open-label study evaluating mivocabtagene autoleucel in patients with ACPA-positive, treatment-refractory active rheumatoid arthritis.