SABLE Registry Supports Long-Term Belimumab Safety in Real-World SLE Management

Five years of prospective real-world follow-up from the global SABLE registry have reinforced belimumab's long-term safety profile in systemic lupus erythematosus (SLE) with adverse events of special interest (AESI) occurring at low rates broadly comparable to those seen with conventional immunosuppressant therapy — and with the time-varying exposure analysis, which more accurately accounts for treatment switching over the follow-up period, showing most AESI incidence rates either numerically lower or similar in the belimumab group versus the non-belimumab group.¹

The findings were presented at SLEuro 2026 by Ronald F. van Vollenhoven, MD, PhD, Chair of the Department of Rheumatology and Clinical Immunology at Amsterdam UMC and Director of the Amsterdam Rheumatology and Immunology Center in Amsterdam, the Netherlands.

SABLE (NCT01729455) is a real-world, prospective, observational registry that enrolled 2,967 patients with active SLE between 2013 and 2020 across a geographically and racially diverse global population, assigning 2,030 to the belimumab (BEL) group and 937 to a conventional immunosuppressant (non-BEL) group, both on background standard therapy. Baseline characteristics were broadly comparable between groups — median age 44.0 years (IQR 35.0–53.0) vs. 43.0 years (IQR 32.0–55.0), 93.5% vs. 89.8% female, median SLE disease duration 8.1 years (IQR 3.5–15.7) vs. 8.4 years (IQR 3.5–16.1), and median SLEDAI-2K 4.0 (IQR 2.0–8.0) vs. 4.0 (IQR 2.0–7.0) — with the notable exception of numerically higher rates of other concomitant autoimmune disorders (27.0% vs. 17.7%) and psychiatric disorders (30.6% vs. 20.5%) in the BEL group, a confounding consideration that the time-varying exposure analysis was designed in part to address.¹

In the initial exposure (ITT) analysis, AESI incidence rates per 100 patient-years over 0–60+ months were numerically lower in the BEL versus non-BEL group for mortality (0.65 [95% CI, 0.48–0.86] vs. 0.83 [95% CI, 0.56–1.20]) and malignancy excluding NMSC (0.60 [95% CI, 0.43–0.80] vs. 0.70 [95% CI, 0.45–1.04]), higher for serious infections (2.37 [95% CI, 2.02–2.76] vs. 1.94 [95% CI, 1.49–2.47]) and serious psychiatric events (0.35 [95% CI, 0.23–0.52] vs. 0.14 [95% CI, 0.05–0.34]), and similar — defined as an incidence rate difference ≤0.1 — for opportunistic infections (0.52 [95% CI, 0.37–0.71] vs. 0.61 [95% CI, 0.38–0.93]), other infections of special interest (0.60 [95% CI, 0.44–0.81] vs. 0.55 [95% CI, 0.33–0.87]), and NMSC (0.14 [95% CI, 0.06–0.25] vs. 0.12 [95% CI, 0.03–0.29]).¹

Critically, the time-varying exposure analysis — which better isolates the effect of belimumab by accounting for post-baseline treatment switching with a 14-week washout — shifted the serious infection and serious psychiatric event findings, with rates becoming either similar or numerically lower in the BEL group: serious infections 2.22 (95% CI, 1.87–2.63) vs. 2.45 (95% CI, 2.00–2.96) and serious psychiatric events 0.31 (95% CI, 0.19–0.48) vs. 0.27 (95% CI, 0.14–0.47), with results consistent between 14-week and 6-month washout strategies — suggesting the ITT signals for those outcomes were at least partly attributable to confounding by treatment switching rather than belimumab exposure itself.¹

RheumatologyLive spoke with Van Vollenhoven to learn more about how these new findings support the use of belimumab, currently approved under the name Benlysta for those over the age of 5 years with with active, autoantibody-positive SLE.²

RheumatologyLive: How does the SABLE registry add to the field’s knowledge of belimumab’s benefit from clinical trials?

van Vollenhoven: With a 5-year duration, SABLE was longer than most clinical trial extensions.
Conventional registry data are usually collected in regular practice (“real world”) but that often means quite limited data that are colored by the practice situation. In contrast, SABLE featured a belimumab-treatment group and a conventional-therapy control group and, while the 2 were generated in practice and not through randomization, they were comparable groups in many ways. Moreover, follow-up and data collection in SABLE were strictly pre-determined, and data collection was monitored and quality-controlled according to GCP standards.
As a result, SABLE can tell us with a great deal of precision about the long-term treatment of belimumab as compared to conventional immunosuppresive therapy, and provides granular and precise data on safety and tolerability aspects over five years of follow-up.

Were there any safety signals that warrant closer monitoring in specific patient subpopulations?

van Vollenhoven: In SABLE all AEs were meticulously recorded using MedDRA, irrespective of whether they were felt to be related or not. MedDRA is a standardized medical dictionary that helps doctors and researchers describe and record side effects in a consistent way, so safety data can be compared and understood reliably. The overall level of adverse events did not differ meaningfully between the two groups and conformed with expectations for such a long-term study. Small numerical differences were seen with infections, in keeping with the well-defined frequencies of infections seen in the original shorter-duration trials. Psychiatric side effects were also considered, as they had been cited as potential safety concerns with belimumab. The data demonstrates that even if there is an identified increase in risk, this is small in absolute numbers and represents only a minor percentage point change. The importance of SABLE is in providing new evidence that can support conversations between physicians and patients when discussing belimumab as a potential new medication.

How should rheumatologists reluctant to continue belimumab beyond 2 or 3 years interpret these findings?

van Vollenhoven: We do not see any cumulative toxicities and no indications that risks increase with time. If the patient has a clear benefit from the treatment, these data provide reassurance that the treatment can be continued for five years (or longer) with a favorable benefit/risk profile.

Editor’s note: this transcript has been edited for clarity. Van Vollenhoven’s disclosures include AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Instituto Científico Pfizer, Janssen Global Services, Kyowa Kirin Co., RemeGen, Sanofi US Services, UCB, Vielabio and Vor Bio, Bristol-Myers Squibb, F. Hoffmann-La Roche and Merck.

References

1. Van Vollenhoven R, Bruce IN, Merrill JT, et al. Five-year safety of belimumab in SLE: insights from the global, prospective, observational SABLE registry. . Presented at 15th European Lupus Meeting; Lisbon, Portugal; March 4-7, 2026.

2. FDA approves GSK’s BENLYSTA as the first medicine for adult patients with active lupus nephritis in the US. News release. GSK. December 15, 2020. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-benlysta-as-the-first-medicine-for-adult-patients-with-active-lupus-nephritis-in-the-us/