B-Cells

Fifteen patients with multidrug-resistant RA received blinatumomab at roughly a tenth of the haematology dose. All 15 achieved at least ACR20 and synovial B cells were depleted, but 14 of 15 flared within a median five months. The more provocative observation is what happened next: seven patients responded for over three months to b/tsDMARDs that had already failed them — raising the possibility that partial depletion resensitises rather than resets.

ALLEGORY is a phase 3 RCT of the type II anti-CD20 antibody obinutuzumab added to standard therapy in active non-renal SLE. It met its primary endpoint (SRI-4 76.7% vs 53.5% at week 52) and all five key secondary endpoints, achieving both steroid-sparing and a ~40% reduction in flare hazard — reinforcing that depth of B-cell depletion matters and that type II succeeds where rituximab failed.

A 2026 narrative review of T-cell engagers (TCEs) in autoimmune rheumatic disease — off-the-shelf bispecific antibodies that redirect a patient’s own T cells against autoreactive B/plasma cells, pitched as a repeatable, dose-adjustable alternative to CAR-T. Early efficacy across SLE, SSc, RA, myositis and Sjögren’s is real but preliminary, and the review’s headline problem is under-dosing relative to oncology, which likely drives frequent relapse.

A 2026 narrative review arguing that B cells are the single through-line of Sjögren disease — connecting autoantibodies, glandular pathology, the highest lymphoma risk of any autoimmune disease, and the emerging drug pipeline. Endotyping by B-cell activity may identify who develops lymphoma and who responds to B-cell-targeted therapy, as newer BAFF/APRIL, CD40L, BTK and FcRn agents succeed where rituximab failed.