Article Text
PDF
Abstract
In comparison to oncologists, rheumatologists have been slow to begin using combinations of drugs in the treatment of the conditions they manage. The most widely used biologic drugs in patients with lupus, rituximab and belimumab, have now been combined in four studies. First, a small study called SYNBIoSe 1 reported that a low disease activity state was achieved in 10/16 patients with no safety signals.1 2 Of the other three studies, BEAT-LUPUS was the most successful.3 A total of 52 patients were treated with rituximab and half had belimumab to follow. The primary endpoint, a reduction in IgG anti-dsDNA antibodies was met and, importantly, the number of flares in patients given both rituximab and belimumab in the one-year follow-up study was just three, compared to ten in those given rituximab and placebo. The CALIBRATE study,4 focusing on lupus nephritis (n=43), was principally a safety study and not powered to look for clinical benefit, and the BLISS-BELIEVE study of 215 patients showed no difference between the patients given belimumab plus rituximab and those given belimumab and placebo.5
These conflicting data mean we cannot, at this point, know for certain if belimumab plus rituximab will be the best approach. It may be that the sequence of giving the antibodies is important and, in this regard, BEAT-LUPUS suggests that rituximab followed by belimumab might be more beneficial for patients with lupus.3 Intriguingly, in BEAT-LUPUS, IgA antibodies to double-stranded DNA proved to be predictive of who was most likely to benefit from rituximab followed by belimumab.6
References
Kraaij T, Kamerling SWA, de Rooij ENM, et al. The net-effect of combining rituximab with belimumab in severe systemic lupus erythematosus. J Autoimmun. 2018;91:45–54. doi: 10.1016/j.jaut.2018.03.003.
Kraaij T, Arends EJ, van Dam LS, et al. Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results. Nephrol Dial Transplant. 2021;36(8):1474–83. doi: 10.1093/ndt/gfaa117.
Shipa M, Embleton-Thirsk A, Parvaz M, et al. Effectiveness of belimumab after rituximab in systemic lupus erythematosus: A randomized controlled trial. Ann Intern Med. 2021;174(12):1647–57. doi: 10.7326/m21-2078.
Atisha-Fregoso Y, Malkiel S, Harris KM, et al. Phase II randomized trial of rituximab plus cyclophosphamide followed by belimumab for the treatment of lupus nephritis. Arthritis Rheumatol. 2021;73(1):121–31. doi: 10.1002/art.41466.
Teng YKO, van Maurik A, Clark KL, et al. OP0281 pharmacodynamic effect of sequential belimumab (BEL) and rituximab (RTX) therapy in patients (PTS) with systemic lupus erythematosus (SLE): The Phase 3, randomised, placebo-controlled BLISS-BELIEVE study. Annals of the Rheumatic Diseases. 2022;81(Suppl 1):186. doi: 10.1136/annrheumdis-2022-eular.2433.
Shipa M, Santos LR, Nguyen DX, et al. Identification of biomarkers to stratify response to B-cell-targeted therapies in systemic lupus erythematosus: An exploratory analysis of a randomised controlled trial. Lancet Rheumatol. 2023;5(1):e24-e35. doi: 10.1016/s2665-9913(22)00332–0.
Learning Objectives At the end of this presentation participants will be able to:
Discuss why rheumatologists have come late to the ‘combination therapy party’
Explain why the four studies of combination therapy have given conflicting results
Explain why the sequence of giving the antibodies is important and thus far rituximab followed by belimumab looks most promising
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/.