Abstract
Background: B cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) refractory to conventional therapy but yields variable responses. We hypothesised that high B cell activating factor (BAFF) levels after rituximab can cause disease flares thereby limiting its effectiveness.
Objective: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE.
Design: Phase II randomised, double-blind (patient, assessors, researchers, providers of care) placebo-controlled, parallel group, superiority trial (ISRCTN: 47873003)
Setting: England
Participants: 52 patients with SLE refractory to conventional treatment, for whom their physician had recommended rituximab therapy, were recruited between February 2, 2017 and March 28, 2019.
Interventions. Participants were treated with rituximab and then 4 to 8 weeks later were randomised (1:1) to receive intravenous belimumab or placebo for 52-weeks.
Measurements The pre-specified primary endpoint was serum IgG anti-dsDNA antibody levels at 52-weeks. Secondary outcomes included incidences of disease flares and adverse events.
Results At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared to placebo (geometric mean 47 IU/ml, 95% CI 25-88 vs 103 IU/ml, 95% CI 49-213, treatment effect 70% greater reduction from baseline, 95% CI 46-84%, p<0·001). Belimumab reduced the risk of severe flare (BILAG A flare) compared to placebo after rituximab (hazard ratio 0·27, 95% CI 0·07 -0·98, log-rank p=0·033), with 10 severe flares in the placebo and 3 in the belimumab group. Belimumab did not increase the incidence of serious adverse events. Belimumab significantly suppressed B cell repopulation compared to placebo (geometric mean 0.012 x109/L, 95% CI 0.006-0.014 vs 0.037 x109/L, 95% CI 0.021-0.081) at 52 weeks in a subset of patients (n=25) where data were available.
Limitations: Small sample size, biomarker primary endpoint.
Conclusion: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced the risk of severe flare in SLE patients who are refractory to conventional therapy. Our results suggest that this combination could be developed as a therapeutic strategy.
Primary Funding Source: Versus Arthritis
Objective: To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE.
Design: Phase II randomised, double-blind (patient, assessors, researchers, providers of care) placebo-controlled, parallel group, superiority trial (ISRCTN: 47873003)
Setting: England
Participants: 52 patients with SLE refractory to conventional treatment, for whom their physician had recommended rituximab therapy, were recruited between February 2, 2017 and March 28, 2019.
Interventions. Participants were treated with rituximab and then 4 to 8 weeks later were randomised (1:1) to receive intravenous belimumab or placebo for 52-weeks.
Measurements The pre-specified primary endpoint was serum IgG anti-dsDNA antibody levels at 52-weeks. Secondary outcomes included incidences of disease flares and adverse events.
Results At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared to placebo (geometric mean 47 IU/ml, 95% CI 25-88 vs 103 IU/ml, 95% CI 49-213, treatment effect 70% greater reduction from baseline, 95% CI 46-84%, p<0·001). Belimumab reduced the risk of severe flare (BILAG A flare) compared to placebo after rituximab (hazard ratio 0·27, 95% CI 0·07 -0·98, log-rank p=0·033), with 10 severe flares in the placebo and 3 in the belimumab group. Belimumab did not increase the incidence of serious adverse events. Belimumab significantly suppressed B cell repopulation compared to placebo (geometric mean 0.012 x109/L, 95% CI 0.006-0.014 vs 0.037 x109/L, 95% CI 0.021-0.081) at 52 weeks in a subset of patients (n=25) where data were available.
Limitations: Small sample size, biomarker primary endpoint.
Conclusion: Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced the risk of severe flare in SLE patients who are refractory to conventional therapy. Our results suggest that this combination could be developed as a therapeutic strategy.
Primary Funding Source: Versus Arthritis
| Original language | English |
|---|---|
| Journal | Annals of internal medicine |
| Volume | 174 |
| Issue number | 12 |
| Early online date | 26 Oct 2021 |
| DOIs | |
| Publication status | Published - Dec 2021 |
Keywords
- Systemic Lupus Erythematosus
- Rituximab
- belimumab