Clinical outcomes in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: a retrospective analysis of results from the OBSErve study in Switzerland
AIMS OF THE STUDY
To describe patterns of systemic lupus erythematosus (SLE) care and the clinical effectiveness of belimumab plus standard of care therapy in a real-world clinical setting in Switzerland.
This multicentre, observational, retrospective cohort study included adults with SLE who initiated belimumab as part of their usual care at least six months before data analysis. The primary outcome was the overall clinical response, assessed by a physician on a Physician’s Global Assessment-like scale, to six months’ treatment with belimumab. Secondary outcomes included improvement in disease activity, SLE manifestations and changes in corticosteroid use.
53 patients (81% female) from three hospitals were included. At index (belimumab initiation), 23 patients (43%) had mild, 23 (43%) had moderate, and 7 (13%) had severe SLE. Overall improvement in disease activity in patients receiving belimumab was: ≥80% in 6 patients (11%), ≥50% in 12 (23%), ≥20% in 31 (58%), <20% in 13 (25%), and no improvement in 9 (17%). Mean Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index score decreased from 8.0 at index to 3.6 at six months post index in the 27 patients assessed. In addition, a ≥50% improvement in arthritis, fatigue, rash, low complement (C3, C4 or total haemolytic complement activity), and anti-double-stranded deoxyribonucleic acid antibody levels was experienced six months post index by 10 (38%), 3 (16%), 6 (38%), 2 (12%) and 4 (16%) patients who presented the manifestations at index respectively. At index, 41 patients (77%) received oral corticosteroids at a mean dose of 11.6 mg/day, which decreased to 5.9 mg/day at six months post index. Of the 31 patients receiving a high dose of corticosteroids (≥7.5 mg/day) at index, 18 required <7.5 mg/day and a further two discontinued corticosteroids at six months post index.
This study provides real-world insight into belimumab use in clinical practice in Switzerland. In line with findings from other countries, Swiss patients with SLE who received belimumab demonstrated clinical and serological improvements in SLE and a reduction in corticosteroid use after six months of treatment.
- D’Cruz DP, Khamashta MA, Hughes GRV. Systemic lupus erythematosus. Lancet. 2007;369(9561):587–96. doi:.https://doi.org/10.1016/S0140-6736(07)60279-7
- Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus. 2006;15(5):308–18. doi:.https://doi.org/10.1191/0961203306lu2305xx
- Bertsias G, Ioannidis JPA, Boletis J, Bombardieri S, Cervera R, Dostal C, et al.; Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis. 2008;67(2):195–205. doi:.https://doi.org/10.1136/ard.2007.070367
- Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam L-S. Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheumatol. 2003;30(9):1955–9.
- Oglesby A, Shaul AJ, Pokora T, Paramore C, Cragin L, Dennis G, et al. Adverse event burden, resource use, and costs associated with immunosuppressant medications for the treatment of systemic lupus erythematosus: a systematic literature review. Int J Rheumatol. 2013;2013:347520. doi:.https://doi.org/10.1155/2013/347520
- Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58(8):2453–9. doi:.https://doi.org/10.1002/art.23678
- Zhang J, Roschke V, Baker KP, Wang Z, Alarcón GS, Fessler BJ, et al. Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001;166(1):6–10. doi:.https://doi.org/10.4049/jimmunol.166.1.6
- Baker KP, Edwards BM, Main SH, Choi GH, Wager RE, Halpern WG, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48(11):3253–65. doi:.https://doi.org/10.1002/art.11299
- Fachinformation Benlysta. 2017. Accessed April 2018.http://www.swissmedicinfo.ch/.
- Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, et al.; BLISS-76 Study Group. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30. doi:.https://doi.org/10.1002/art.30613
- Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al.; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31. doi:.https://doi.org/10.1016/S0140-6736(10)61354-2
- Zhang F, Bae S-C, Bass D, Chu M, Egginton S, Gordon D, et al. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018;77(3):355–63. doi:.https://doi.org/10.1136/annrheumdis-2017-211631
- Babini AGM, Barreira JC, Pons-Estel B, Iglesias M, Streger G. Evaluation of use of belimumab in clinical practice settings: Results in Argentina. Arthritis Rheum. 2016;68(Suppl 10).
- Collins CE, Dall’Era M, Kan H, Macahilig C, Molta C, Koscielny V, et al. Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA. Lupus Sci Med. 2016;3(1):e000118. doi:.https://doi.org/10.1136/lupus-2015-000118
- Cortes JMC, Andreu J, Calvo-Alen J, Garcia-Aparicio A-M, Alvarez ED, et al. Evolution of patients with systemic lupus erythematous treated with belimumab in clinical practice settings. Arthritis Rheumatol. 2014;66(Suppl 11):S291.
- Schwarting A, Schroeder JO, Alexander T, Schmalzing M, Fiehn C, Specker C, et al. First real-world insights into belimumab use and outcomes in routine clinical care of systemic lupus erythematosus in Germany: Results from the OBSErve Germany study. Rheumatol Ther. 2016;3(2):271–90. doi:.https://doi.org/10.1007/s40744-016-0047-x
- Touma Z, Sayani A, Pineau CA, Fortin I, Matsos M, Ecker GA, et al. Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study. Rheumatol Int. 2017;37(6):865–73. doi:.https://doi.org/10.1007/s00296-017-3682-9
- von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. doi:.https://doi.org/10.1016/S0140-6736(07)61602-X
- ICH. Guideline for good clinical practice 2016. Accessed March 2018.https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf.
- ISPE. Guidelines for Good Pharmacoepidemiology Practices 2015. Accessed March 2018.https://www.pharmacoepi.org/resources/policies/guidelines-08027/.
- Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH, Austin A, et al.; The Committee on Prognosis Studies in SLE. Derivation of the SLEDAI. A disease activity index for lupus patients. Arthritis Rheum. 1992;35(6):630–40. doi:.https://doi.org/10.1002/art.1780350606
- Gladman DD, Urowitz MB, Kagal A, Hallett D. Accurately describing changes in disease activity in Systemic Lupus Erythematosus. J Rheumatol. 2000;27(2):377–9.
- Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991;34(8):937–44. doi:.https://doi.org/10.1002/art.1780340802
- EMA. Benlysta Summary of Product Characteristics (SmPC). Accessed March 2017;http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002015/WC500110150.pdf.
- Ruiz-Arruza I, Ugarte A, Cabezas-Rodriguez I, Medina JA, Moran MA, Ruiz-Irastorza G. Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2014;53(8):1470–6. doi:.https://doi.org/10.1093/rheumatology/keu148
- Ruiz-Arruza I, Lozano J, Cabezas-Rodriguez I, Medina JA, Ugarte A, Erdozain JG, et al. restrictive use of oral glucocorticoids in systemic lupus erythematosus and prevention of damage without worsening long-term disease control: An observational study. Arthritis Care Res (Hoboken). 2018;70(4):582–91. doi:.https://doi.org/10.1002/acr.23322
- Gutiérrez-Suárez R, Ruperto N, Gastaldi R, Pistorio A, Felici E, Burgos-Vargas R, et al. A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum. 2006;54(9):2989–96. doi:.https://doi.org/10.1002/art.22048
- van Vollenhoven RF, Petri MA, Cervera R, Roth DA, Ji BN, Kleoudis CS, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9. doi:.https://doi.org/10.1136/annrheumdis-2011-200937
- Furie RA, Wallace DJ, Aranow C, Fettiplace J, Wilson B, Mistry P, et al. Long-Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus: A Continuation of a Seventy-Six-Week Phase III Parent Study in the United States. Arthritis Rheumatol. 2018;70(6):868–77. doi:.https://doi.org/10.1002/art.40439
- Strand V, Gladman D, Isenberg D, Petri M, Smolen J, Tugwell P. Outcome measures to be used in clinical trials in systemic lupus erythematosus. J Rheumatol. 1999;26(2):490–7.
- van Vollenhoven RF, Mosca M, Bertsias G, Isenberg D, Kuhn A, Lerstrøm K, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73(6):958–67. doi:.https://doi.org/10.1136/annrheumdis-2013-205139