Publication Digests

BLISS-BELIEVE

Systemic lupus erythematosus (SLE) disease control, both in terms of disease remission and health-related quality of life, continues to be an unmet need in SLE treatment^1,2. Belimumab is approved for the treatment of SLE^2,3. Rituximab is still in the treatment armamentarium for SLE despite poor trial results for lupus nephritis and extrarenal lupus². Belimumab and rituximab work through complementary mechanisms, hypothesised to result in enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes². This led to development of the phase 3, randomised, placebo-controlled BLISS-BELIEVE study, investigating the efficacy and safety of a belimumab and rituximab combination treatment in people with SLE^1,2,4. The design and results of this study are summarised in the infographic below¹.

Limiting organ damage in Lupus

Belimumab is a human IgG1-λ monoclonal antibody used in the treatment of SLE. Previous clinical trials showed belimumab efficacy versus placebo in adults with active, autoantibody-positive SLE receiving standard therapy over 52 and 76 weeks⁵. Patients who completed the belimumab International SLE Study (BLISS)-52 or BLISS-76 were eligible to continue open-label treatment with belimumab this long-term extension study to evaluate safety, tolerability and long-term organ damage accrual. The results of this study demonstrated that belimumab is safe for long-term use with minimal adverse events causing discontinuation of treatment, and that organ damage caused by disease progression can be prevented⁶.

Managing Lupus Nephritis

Lupus nephritis represents a major cause of morbidity and mortality in systemic lupus erythematosus, affecting 25–60% of patients⁷. In previous clinical trials, belimumab appeared to decrease proteinuria and reduce the incidence of renal flares among patients with proteinuria at baseline⁸. Based on these observations, the Belimumab International Study in Lupus Nephritis (BLISS-LN) was carried out specifically to assess the efficacy and safety of belimumab in patients with active lupus nephritis⁵. The results of this study, which led to FDA approval of belimumab for the treatment of lupus nephritis in December 2020, are summarised in the infographic below⁹.

Long-term organ damage and new treatments for SLE

The 2019 update of the European Alliance of Associations of Rheumatology recommendations for systemic lupus erythematosus (SLE) care emphasises the importance of organ damage prevention¹⁰, which is a critical consideration given that over half of people with SLE develop organ damage^11,12. Accumulated organ damage is associated with poorer health outcomes¹¹, and patients with damage are at higher risk of future mortality¹³.

It is common for disease activity to persist despite administration of currently approved therapies, and the toxicity of therapies such as glucocorticoids can impact quality of life¹⁴. New and emerging treatments seek to address these gaps. This infographic summarises organ damage in SLE and addresses new and emerging treatment approaches such as monoclonal antibodies, immunomodulators and kinase inhibitors.

References

1. Aranow C, Allaart C, Amoura Z, Bruce I, Cagnoli P, Furie R, et al. Efficacy and Safety of Subcutaneous Belimumab (BEL) and Rituximab (RTX) Sequential Therapy in Patients with Systemic Lupus Erythematosus: The Phase 3, Randomized, Placebo-Controlled BLISS-BELIEVE Study. Presented at the ACR Convergence 2021. L13. Available at: https://acrabstracts.org/abstract/efficacy-and-safety-of-subcutaneous-belimumab-bel-and-rituximab-rtx-sequential-therapy-in-patients-with-systemic-lupus-erythematosus-the-phase-3-randomized-placebo-controlled-bliss-believe-stud/. Accessed 18 January 2023.
2. Teng YKO, Bruce IN, Diamond B, Furie RA, Van Vollenhoven RF, Gordon D, et al. Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. BMJ Open. 2019;9(3):e025687.
3. Belimumab Summary of Prescribing Information. https://www.medicines.org.uk/emc/product/11398/smpc#INDICATIONS. Accessed 18 January 2023.
4. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE. https://clinicaltrials.gov/ct2/show/NCT03312907. Accessed 18 January 2023.
5. Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. New England Journal of Medicine. 2020;383(12):1117-1128.
6. van Vollenhoven RF, Navarra SV, Levy RA, Thomas M, Heath A, Lustine T, et al. Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension. Rheumatology. 2020;59(2):281-291.
7. Hanly JG, O'Keeffe AG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, et al. The frequency and outcome of lupus nephritis: Results from an international inception cohort study. Rheumatology (United Kingdom). 2015;55(2):252-262.
8. Dooley MA, Houssiau F, Aranow C, D'Cruz DP, Askanase A, Roth DA, et al. Effect of belimumab treatment on renal outcomes: Results from the phase 3 belimumab clinical trials in patients with SLE. Lupus. 2013;22(1):63-72.
9. gsk.com. FDA approves GSK’s BENLYSTA as the first medicine for adult patients with active lupus nephritis in the US. . 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/. Accessed 5 May 2021.
10. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78:736-745.
11. Murimi-Worstell IB, Lin DH, Nab H, Kan HJ, Onasanya O, Tierce JC, et al. Association between organ damage and mortality in systemic lupus erythematosus: A systematic review and meta-analysis. BMJ Open. 2020;10(5):e031850-e031850.
12. González LA, Santamaría-Alza Y, Alarcón GS. Organ damage in systemic lupus erythematosus. Revista Colombiana de Reumatologia. 2021;28:66-81.
13. Bruce IN, O'Keeffe AG, Farewell V, Hanly JG, Manzi S, Su L, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Annals of the Rheumatic Diseases. 2015;74(9):1706-1713.
14. Tsang-A-Sjoe MWP, Bultink IEM. New developments in systemic lupus erythematosus. Rheumatology. 2021;60(Supplement_6):vi21-vi28.