You are here

  • Home
  • Archive
  • Volume 83, Issue 11
  • Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study

Article Text

Article menu
Systemic lupus erythematosus
Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study
  1. Cynthia Aranow1,
  2. Cornelia F Allaart2,
  3. Zahir Amoura3,
  4. Ian N Bruce4,5,
  5. Patricia C Cagnoli6,
  6. Walter W Chatham7,
  7. Kenneth L Clark8,
  8. Richard Furie1,
  9. James Groark9,
  10. Murray B Urowitz10,
  11. Ronald van Vollenhoven11,
  12. Mark Daniels12,
  13. Norma Lynn Fox9,
  14. Yun Irene Gregan13,
  15. Robert B Henderson14,
  16. André van Maurik14,
  17. Josephine C Ocran-Appiah15,
  18. Mary Oldham16,
  19. David A Roth17,
  20. Don Shanahan18,
  21. Paul P Tak19,
  22. Yk Onno Teng20
  1. 1 Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
  2. 2 Leids Universitair Medisch Centrum, Leiden, The Netherlands
  3. 3 Assistance Publique–Hôpitaux de Paris, Groupement Hospitalier Pitié–Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France
  4. 4 Kellgren Centre for Rheumatology, Manchester University Hospitals NHS Trust, Manchester, UK
  5. 5 Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  6. 6 University of Michigan Medical Center, Ann Arbor, Michigan, USA
  7. 7 University of Alabama at Birmingham, Birmingham, Alabama, USA
  8. 8 Clinical Science, GSK, Stevenage, UK
  9. 9 Clinical Development, GSK, Collegeville, Pennsylvania, USA
  10. 10 Toronto Western Hospital, University of Toronto, Lupus Clinic, Toronto, Ontario, Canada
  11. 11 Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, The Netherlands
  12. 12 Global Medical Affairs, GSK, Brentford, UK
  13. 13 Clinical Science Immunology, GSK, Collegeville, Pennsylvania, USA
  14. 14 Clinical Biomarker Group, GSK, Stevenage, UK
  15. 15 Clinical Science, Respiratory and Immunology Clinical Research and Early Programs, GSK, Philadelphia, Pennsylvania, USA
  16. 16 Biostatistics, GSK, Stevenage, UK
  17. 17 Research and Development, GSK, Collegeville, Pennsylvania, USA
  18. 18 Development Biostatistics, GSK, GSK House, Brentford, UK
  19. 19 Research and Development, GSK, Stevenage, UK
  20. 20 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Cynthia Aranow; caranow@northwell.edu

Abstract

Objectives Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).

Methods In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included. Primary endpoint: proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets.

Results The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO.

Conclusions BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted.

Trial registration number NCT03312907.

  • Autoimmune Diseases
  • Biological Therapy
  • B-Lymphocytes
  • Lupus Erythematosus, Systemic
  • Rituximab

Data availability statement

Data are available upon reasonable request. GSK is committed to publicly disclosing the results of GSK-sponsored clinical research that evaluates GSK medicines, and as such was involved in the decision to submit the results of this study (GSK Study 205646). Anonymised individual patient data and study documents can be requested for further research from https://www.gsk-studyregister.com/en/.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/ard-2024-225686

Statistics from Altmetric.com

Data availability statement

Data are available upon reasonable request. GSK is committed to publicly disclosing the results of GSK-sponsored clinical research that evaluates GSK medicines, and as such was involved in the decision to submit the results of this study (GSK Study 205646). Anonymised individual patient data and study documents can be requested for further research from https://www.gsk-studyregister.com/en/.

View Full Text

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Handling editor Josef S Smolen

  • Contributors Conception or design: INB, RF, JG, RvV, NLF, RBH, AvM, MO, DAR, PPT and YOT. Acquisition of data: CA, CFA, ZA, PCC, WWC and MBU. Data analysis or interpretation: CA, CFA, ZA, INB, PCC, WWC, KLC, RF, JG, MBU, RvV, MD, MO, NLF, YIG, AvM, JCO-A, DAR, DS, PPT and YOT. JCO-A is guarantor for this publication (KLC, JG, MD, NLF, YIG, DS, PPT: at the time of the author’s contribution to this study).

  • Funding This study (GSK Study 205646) was funded by GSK.

  • Competing interests CA has received research support from GSK; consulting fees from GSK, AstraZeneca, BMS, Kezar Life Sciences Inc., Merck Sharp & Dohme and Alumis Inc. CFA has received research support from Janssen, AbbVie, and Eli Lilly. ZA has received research support from GSK, Roche, AstraZeneca, and Amgen; and consulting fees from GSK, AstraZeneca, Amgen, Kezar Life Sciences Inc, and Novartis. INB has received research support from Genzyme, Sanofi, and GSK; consulting fees from AstraZeneca, Eli Lilly, Aurinia Pharmaceuticals, GSK, and ILTOO; and has served as an advisory board member for AstraZeneca and Merck Serono. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is funded by the NIHR Manchester Biomedical Research Centre (NIHR203308). PCC has received consulting and speaker fees from GSK, Aurinia Pharmaceuticals, and Eli Lilly. WWC has received research support from GSK, UCB, Amgen, Pfizer, and BMS; consulting fees from GSK and Aurinia Pharmaceuticals; honoraria from GSK and Aurinia Pharmaceuticals for disease awareness presentations and curricula on achieving disease control and remission in SLE. RF has received research support and consulting fees from GSK. MBU has received research support from GSK; consulting fees from GSK and UCB; and speaker fees from GSK, Eli Lilly, and AstraZeneca. RvV has received research support for educational programmes and institutional grants from AstraZeneca, Pfizer, and UCB; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio; speaker fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, and UCB; and research support from BMS, GSK Eli Lilly, and UCB. RBH, AvM, JCO-A, MO and DAR are employees of GSK and hold stocks and shares in the company. RBH is also an inventor for the following patents: US-20220195062-A1, US-11180569-B2, and US-20180265588-A1. KLC, JG, MD, YIG, DS and PPT were employees of GSK at the time of the study and hold stocks and shares in the company. NLF is a former employee and consultant for GSK and holds stocks in the company. YOT has received unrestricted research grants from GSK, Aurinia Pharmaceuticals, and Vifor Pharma; and consulting fees from Aurinia Pharmaceuticals, Novartis, GSK, Kezar Life Sciences Inc, Vifor Pharma, and Otsuka Pharmaceuticals (paid to Leiden University Medical Center).

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.