B-cell depletion in rheumatoid arthritis and lupus treatment

Irish Society for Rheumatology Autumn Meeting, Radisson Blu Hotel, Little Island, Cork, 18-19 September 2025

The Irish Society of Rheumatology (ISR) Autumn Meeting was held at the Radisson Blu Hotel, Cork, last month. A large group of delegates came together for the event, which featured an array of speakers on a wide breadth of topics related to rheumatology. The programme opened with a clinical advisory group meeting before outgoing ISR President Dr John Ryan welcomed attendees and the programme commenced.

Following oral presentations of the top six abstracts, Prof Chris Edwards, Consultant Rheumatologist and Honorary Chair of Clinical Rheumatology, NIHR Southampton Clinical Research Facility, University Hospital Southampton, UK, took to the podium for his presentation on B-cell depletion in rheumatoid arthritis (RA) and lupus treatment.

Prof Edwards opened his talk by describing the strategies for optimal management of immune-mediated inflammatory diseases. He stressed the importance of early treatment, tight control, and setting a target, along with therapeutic choices.

Prof Edwards told attendees that multiple therapeutic options are required to provide the best treatment possible, because not every patient responds to first-line therapy.

He highlighted the number of therapies available to treat chronic inflammatory diseases such as RA and psoriasis, and provided an overview on licensing, effectiveness and disease aggravating effects for each disease.

Prof Edwards discussed the rationale for B-cell depletion, including the central role of B-cells in pathogenesis, the differences in B-cell involvement in RA compared to systemic lupus erythematosus (SLE), and the hypothesis that depleting pathogenic B-cells leads to reduced autoimmunity.

He outlined some clinical considerations for RA and lupus, stressing the difficulty in selecting the “best patients for therapy” and the need to understand side-effects.

Prof Edwards referred to the newly published EULAR recommendations for the management of RA, which continue to recommend methotrexate and short-term glucocorticoids as the first-line treatment. If methotrexate is ineffective, a disease-modifying anti-rheumatic drug  (DMARD), such as leflunomide or sulfasalazine, should be commenced. If this line of treatment remains ineffective, the DMARD or JAK inhibitor should be changed, he advised.

Prof Edwards then went on to discuss the 2023 EULAR update on recommendations for the management of SLE and the role of B-cells, before turning to recent clinical evidence and trials conducted in RA.

Trials of the B-cell-directed therapy belimumab have been positive, but there have been less than positive outcomes with ocrelizumab and rituximab in lupus, he noted, adding that deeper B-cell depletion could potentially be required in certain cases.

New strategies and therapies for deeper B-cell depletion include obinutuzumab, ocrelizumab, ofatumumab, belimumab, and other emerging approaches, such as CAR T-cell therapy and bispecific T-cell engager therapy, which involves killing B-cells by engaging T-cells.

Clinicians must grapple with how to treat each patient when there are so many treatment choices and considerations around what strategy to employ and how long to treat for, Prof Edwards remarked.