TOPLINE

Low-dose blinatumomab induced short-term clinical remission and reduction in disease activity in patients with multidrug-resistant rheumatoid arthritis (RA), depleting synovial B cells and reducing synovitis. After experiencing disease flares, a subset of patients responded to disease-modifying antirheumatic drugs (DMARDs) they had previously not responded to.

METHODOLOGY

• Researchers conducted a case series involving 15 patients (median age, 55 years; 60% women) with active multidrug-resistant RA recruited at a center in Germany who were refractory to methotrexate and at least three targeted synthetic or biologic DMARDs.
• Patients had high baseline disease activity (median 28-joint disease activity score C-reactive protein, 5.03; clinical disease activity index [CDAI], 28), with a median disease duration of 13 years.
• Participants received two or three cycles of low-dose blinatumomab (cumulative dose range, 77-189 µg) through 96-hour continuous infusion per cycle, separated by therapy-free periods.
• Therapy-related side effects such as cytokine release syndrome (CRS), immune effector cell-related neurotoxicity syndrome (ICANS), cardiotoxicity, and infections were assessed during the treatment and over 12 months after treatment.
• Synovitis was assessed via ultrasonography and fibroblast activation via fibroblast activation protein inhibitor PET-CT.

TAKEAWAY

• Three low-grade CRS cases occurred, which resolved with the use of metamizole in one patient and single-dose 8 mg/kg tocilizumab in two patients; no ICANS cases were noted. Mild infections developed in 26.6% of patients, with no severe infections noted. A patient with preexisting coronary artery disease and extensive smoking history experienced a fatal cardiovascular event at 1 year, classified as treatment-unrelated by investigators; no independent review was conducted.
• At 12 weeks, disease activity reduced substantially: In terms of CDAI, 9 of 15 patients attained low disease activity or better and 3 of 15 attained remission; all patients demonstrated at least an American College of Rheumatology 20% improvement (ACR20) response, with 73% attaining at least ACR50.
• After initial responses, 14 of 15 patients developed RA flares; one continued to be in drug-free remission at 9 months. Nine patients received retreatment with previously used biologic or targeted synthetic DMARDs (n = 6) or alternative same-class agents (n = 3); seven achieved clinical responses lasting over 3 months.
• B cells were depleted in 4 of 5 synovial biopsies performed at a median of 100 days after treatment, whereas in inguinal lymph nodes biopsies performed at a median of 34 days, B cell counts decreased without being completely depleted. Synovitis also reduced.

IN PRACTICE

"[A]lthough immune reset remains the aspirational goal for curative autoimmunity treatments, low-dose protocols could represent a pragmatic and immediately valuable clinical advancement," the authors of the study wrote.

SOURCE

The study was led by Laura Bucci, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. It was published online on August 13 in Annals of the Rheumatic Diseases.

LIMITATIONS

The study was exploratory in nature. Early improvements in patients might partially be due to the anti-inflammatory effects of glucocorticoids. Timing variations in biopsies may have led to the active B-cell repopulation being sampled instead of the posttreatment residual tissue burden, affecting comparisons of how effectively B cells were depleted from the synovium and lymph nodes.

DISCLOSURES

The study was supported by the Deutsche Forschungsgemeinschaft through various awards and programs, the Lupus Research Alliance, the Else Kröner-Fresenius-Stiftung, the Interdisciplinary Centre for Clinical Research Erlangen, the Boehringer Ingelheim Foundation, the European Union, and the Staedtler Foundation. This research received additional funding through donations from the Bendel and Bleyl families. Some authors reported receiving consulting fees, research support, or speaking fees from multiple pharmaceutical companies, including AbbVie, Amgen, Bristol-Myers Squibb Company, and others.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.