Impact of concomitant medication use on belimumab efficacy and safety in patients with systemic lupus erythematosus

Abstract

Practicing physicians have requested efficacy and safety data for belimumab, when used with specific systemic lupus erythematosus (SLE) medications. This was a post hoc analysis of pooled efficacy and safety data from patients who received belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III, randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four groups based on baseline concomitant medication usage: steroids only; antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants (IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over time and individual SRI components were secondary endpoints. Time to first flare and changes in concomitant medications were exploratory endpoints. Safety was assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77, 9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4–7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the percentage of SRI responders was greatest in the steroids + AM group for belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI component improvements were also observed across other groups. The probability of experiencing an SLE flare was reduced in the steroids-only group for patients who received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio 0.64; 95% confidence interval: 0.42–0.96). There was little or no change in daily AM or IS dose in any group. For all groups, there was a general decrease in steroid dose over time; a quarter to a third of patients experienced decreased steroid doses at Week 52. The overall safety profile was similar across treatment arms and concomitant medication groups, with the exception of serious AEs in the steroids + AM group (belimumab 10 mg/kg 16%, placebo 8%). The efficacy and safety of belimumab in combination with SoC was demonstrated for various groupings of steroids, AM and IS. These findings may improve the understanding of the safety and efficacy of adding belimumab to different treatments.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset

“…[14][15][16] By contrast, hydroxychloroquine seems to have a beneficial effect on damage accrual and long-term prognosis in SLE, 17,18 and the monoclonal antibody belimumab is associated, among other beneficial effects, with steroid sparing. 19,20 In Table 2, the therapy of SLE patients from other observational lupus cohorts is reported, confirming that glucocorticoids are too frequently given to lupus patients across several countries. These data suggest that clinicians should frequently and carefully assess their therapeutic strategies for lupus patients, try to avoid or minimize steroid usage, and take advantage of safer drugs.…”

“…Cardiovascular risk factors and glucocorticoids are both associated with a worse prognosis in lupus patients, being negative factors for long term morbidity and mortality (14)(15)(16). By contrast, hydroxychloroquine seems to have a beneficial effect on damage accrual and long-term prognosis in SLE (17,18), and the monoclonal antibody Belimumab is associated, among other beneficial effects, with steroid sparing (19,20). In table 6 the therapy of SLE patients from other observational lupus cohorts is reported, confirming that glucocorticoids are too much frequently given to lupus patients across several countries.…”

The use of non‐transplant biologics in solid organ transplant recipients: A practical review for the frontline clinician

“…61 Belimumab has been studied extensively in non-transplant patients with SLE along with concomitant mycophenolate, azathioprine, and steroids and revealed similar safety between those receiving steroids alone and steroids plus anti-malarials. 62 However, in a case report of a patient who continued pre-transplant belimumab along with belatacept after alemtuzumab induction complications including neutropenia, bronchitis, and grade 1a acute cellular rejection occurred. 60…”

“…A similar study using alemtuzumab along with belimumab in sensitized KT recipients is currently enrolling to evaluate the efficacy and safety of belimumab in preventing the production of de novo donor specific antibodies; however, no results have been reported 61 . Belimumab has been studied extensively in non‐transplant patients with SLE along with concomitant mycophenolate, azathioprine, and steroids and revealed similar safety between those receiving steroids alone and steroids plus anti‐malarials 62 . However, in a case report of a patient who continued pre‐transplant belimumab along with belatacept after alemtuzumab induction complications including neutropenia, bronchitis, and grade 1a acute cellular rejection occurred 60 …”

Belimumab: therapeutic mechanism and current status of clinical trials

“…van Vollenhoven et al studied the effect of belimumab on corticosteroid dose in SLE patients and found that cumulative corticosteroid dose was substantially smaller than placebo group indicating the belimumab may be steroid sparing [31]. Schwarting et al demonstrated the efficacy and safety of belimumab in combination with standard of care for different grouping of steroid, anti-malarials, and immunosuppressants and observed that overall safety was similar across concomitant medication groups except serious adverse events in the steroids plus antimalarial group [32]. Strand et al have reported the effects of belimumab treatment and standard SLE therapy and found that the disease activity has in fact reduced along with improvement in health related quality of life [33].…”