DOI: 10.1177/09612033261506790 ISSN: 0961-2033

Patient selection for advanced B-cell-targeted therapy trials in systemic lupus erythematosus

Iftach Sagy, Rona M. Smith, Sapna Trivedi, Hugo Tordesillas, David R. W. Jayne, Rachel B. Jones
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Background

A proportion of patients with systemic lupus erythematosus (SLE) remain refractory to standard therapies. Advanced B-cell-targeted therapies (ABT), including chimeric antigen receptor T-cell therapy, T-cell–engaging approaches, and anti-CD19 monoclonal antibodies, are emerging for selected patients in clinical trials.

Methods

We conducted a single-centre observational study of patients with SLE treated with biologic therapies at a tertiary lupus service between January 2024 and December 2025, during active recruitment to ABT clinical trials. We assessed clinical factors associated with referral for multidisciplinary team (MDT) discussion regarding ABT and explored documented reasons for non-participation. We compared patients discussed at ABT-MDT with those not referred within the same cohort.

Results

Among 101 patients treated with biologics, 21 (20.8%) were discussed at ABT-MDT. Patients referred for ABT-MDT had higher rates of lupus nephritis (90.5% vs 46.2%, p < 0.001), higher SLEDAI-2K scores (16.0 vs 2.0, p < 0.001), higher daily prednisolone doses (15.0 vs 1.0 mg, p < 0.001), and greater exposure to prior immunosuppressive therapies. In multivariable analysis, higher SLEDAI-2K (OR 1.92 per 4-point increase, 95% CI 1.10–4.27) and prednisolone dose (OR 3.44 per 5-mg increase, 95% CI 1.23–14.50) were independently associated with ABT-MDT referral. Of those discussed, 7 patients proceeded to ABT. Reasons for non-participation included patient preference, perceived infection risk, clinical improvement, and protocol-related constraints.

Conclusion

In a tertiary SLE cohort, referral for advanced B-cell-targeted therapies was associated with markers of high disease activity and renal involvement. However, multiple clinical and patient-related factors limited trial participation. These findings highlight important considerations in referral and trial participation for advanced B-cell-targeted therapies.

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