Immunosuppressants may not boost belimumab monotherapy in SLE

medwireNews: Patients with systemic lupus erythematosus (SLE) treated with belimumab monotherapy have similar disease control, flare, and treatment response rates as those given the drug in combination with immunosuppressant therapy, suggest real-world registry data.

“While these data support the potential of [belimumab] monotherapy as a reasonable option in selected patients, they should be interpreted with caution given the observational nature of the study,” write José Gómez-Puerta (Hospital Clínic de Barcelona, Spain) and colleagues in Rheumatology.

“Prospective research is needed to confirm these observations and to better identify patient subgroups that may benefit from combined therapeutic approaches.”

The investigators note that both clinical trials and real-world data have shown that belimumab, a monoclonal antibody targeting B-lymphocyte stimulator, reduces disease activity, flare rates, and glucocorticoid exposure in patients with SLE when added to standard of care.

However, in routine clinical practice the drug is often administered in combination with therapies such as conventional immunosuppressants, including mycophenolate mofetil, azathioprine, or methotrexate, they say, even though “the added clinical value of concomitant [immunosuppressant therapy] remains uncertain.”

To investigate further, the researchers prospectively collected data on 258 adults with SLE from the nationwide Spanish Belimumab Registry who had completed at least 12 months of the inhibitor therapy and had information on concomitant immunosuppressant use at the 12-month visit.

The mean age of the participants at initiation of belimumab was 41.9 years, and the average disease duration was 11.4 years. The majority (91.5%) were women.

The team reports that 31.4% of patients were receiving belimumab monotherapy, while 68.6% were taking belimumab combined with immunosuppressant therapy. Individuals treated with monotherapy were significantly less likely than those given combination therapy to have hematologic and renal involvement, and were significantly less likely to have cutaneous manifestations, such as rash and oral/nasal ulcers.

At baseline, the mean SLE Disease Activity Index (SLEDAI) 2000 scores were a comparable 10.3 points in the belimumab monotherapy group and 9.1 points in the concomitant immunosuppressant group, indicating moderate-to-high disease activity in both cases.

By 6 months, disease activity had significantly decreased in both groups and there was no significant difference in SLEDAI scores, at a mean of 3.9 points in the belimumab monotherapy group and 4.8 points in the concomitant immunosuppressant group. There were also no significant differences in the proportion of patients achieving 2021 Definition of Remission In SLE (DORIS) criteria, at 37.8% versus 28.6%, nor Lupus Low Disease Activity state (LLDAS), at 62.2% versus 51.2%.

At 12 months, the SLEDAI scores declined further to 2.9 points and 3.8 points in the belimumab monotherapy and concomitant immunosuppressant groups, respectively. While this was a significant difference in favor of monotherapy, the overall reductions in scores from baseline were comparable (6.1 vs 6.5 points respectively), as were DORIS 2021 remission rates (51.4 vs 48.1%), LLDAS attainment (74.0 vs 65.0%), and severe flare rates (2.6 vs 5.8%).

Propensity score-adjusted analysis was performed to account for age at belimumab initiation, disease duration, baseline SLEDAI scores, glucocorticoid dose, and the number of flares in the year prior to starting belimumab. In logistic regression analysis, there was no significant difference between the monotherapy and combination therapy groups in the primary outcome for the analysis of DORIS remission rates at 12 months, at an odds ratio of 0.89. There were also no differences in remission rates between those who maintained, initiated, or discontinued immunosuppressant therapy during the 12-month follow-up.

Gómez-Puerta and team acknowledge that the observational nature of the study and reliance on data from a multicenter registry contains “inherent limitations, including potential selection bias, residual confounding, and variability in clinical practice patterns across centres.”

Nevertheless, they conclude: “These results may aid in identifying patient subgroups for whom [belimumab] monotherapy represents a reasonable therapeutic option in clinical practice, at least in non-renal SLE.”

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Rheumatology 2026; doi:10.1093/rheumatology/keag076