Laura Bucci, Melanie Hagen, Sebastian Böltz, Carlo Tur, Danae-Mona Nöthling, Tobias Dashi, Janina Auth, Tobias Rothe, Andreas Wirsching, Jochen Wacker, Futoshi Iwata, Andrea Zoli, Anna-Maria Liphardt, Stefano Alivernini, Luis Munoz, Verena Schönau, Jürgen Rech, Armin Atzinger, Maria-Antonietta D'Agostino, Aline Bozec, Markus Eckstein, Maria Gabriella Raimondo, Georg Schett, Ricardo Grieshaber-Bouyer
Short-term control of RA disease activity, depleted synovial B cells, and reduced fibroblast activation on FAPI-PET were observed 3 months after blinatumomab. Flares after blinatumomab responded to previously ineffective disease-modifying antirheumatic drugs in some patients. Low-dose TCE therapy may offer an accessible path to disease control in MDR-RA, although causal inference and generalisability require validation in controlled trials.
OBJECTIVES: T-cell engagers (TCEs) are well-established treatments in haematology; strategies in autoimmune diseases are evolving. As an alternative to high-dose protocols optimising depletion, lower-dose protocols might optimise safety.
METHODS: We assessed safety and efficacy of low-dose blinatumomab in a named patient use case series of 15 patients (median age 55) with multidrug-resistant rheumatoid arthritis (MDR-RA) (28-joint disease activity score C-reactive protein 5.0; clinical disease activity index [CDAI] 28). We monitored safety (cytokine release syndrome [CRS]; immune effector cell-related neurotoxicity syndrome [ICANS]), clinical scores, and tissue inflammation via ultrasound and fibroblast activation protein inhibitor (FAPI)-positron emission tomography/computed tomography (PET/CT). B-cell depletion was quantified in blood, synovium, and lymph nodes.
RESULTS: CRS (grade 1) occurred in 3 of 15 patients. No ICANS occurred. One patient developed hypogammaglobulinaemia. One fatal cardiovascular event occurred after 1 year; it was adjudicated as unrelated by treating investigators but not independently reviewed. By week 12, disease activity decreased; 9 of 15 patients achieved CDAI low disease activity, and 3 of 15 patients achieved CDAI remission. Synovial B cells were depleted (4 of 5 biopsies) but not in lymph nodes. FAPI PET/CT showed reduced tracer uptake in the involved joints after blinatumomab. Although 14 of 15 patients flared, disease activity remained lower, and responsiveness lasting >3 months to previously failed drugs (Janus kinase inhibitors, abatacept, tumour necrosis factor inhibitors) was observed in 7 of 15 patients.
CONCLUSIONS: Short-term control of RA disease activity, depleted synovial B cells, and reduced fibroblast activation on FAPI-PET were observed 3 months after blinatumomab. Flares after blinatumomab responded to previously ineffective disease-modifying antirheumatic drugs in some patients. Low-dose TCE therapy may offer an accessible path to disease control in MDR-RA, although causal inference and generalisability require validation in controlled trials.