Belimumab In Patients Research Articles

Efficacy and safety of belimumab during maintenance therapy in patients with systemic lupus erythematosus.

ObjectivesThe efficacy of belimumab (BEL) during maintenance therapy in patients with SLE remains unclear in the real-life clinical setting. This study investigated the efficacy and safety of BEL in patients with SLE during maintenance therapy.MethodsIn this retrospective observational study, maintenance therapy was defined as low-dose glucocorticoid (GC) therapy (prednisolone equivalent dose of ≤0.2 mg/kg/day) in patients with a Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score <10. Participants comprised patients with SLE on HCQ or MMF [standard-of-care (SoC) group: n = 103] and those on BEL plus SoC (BEL+SoC group: n = 100). Selection bias was minimized using propensity score-based inverse probability of treatment weighting (IPTW). GC dose trajectories were modelled using growth mixture modelling (GMM). The primary end point was GC dose at 52 weeks.ResultsNo significant difference was observed in patient characteristics between the two groups after IPTW adjustment. The BEL+SoC group exhibited a significant decrease in GC dose. GC dose at 52 weeks and relapse rate were significantly lower in the BEL+SoC group than in the SoC group. The proportion of patients in one of four groups defined by GMM for which GC dose was tapered to 0 mg within 52 weeks (GC tapering-discontinuation group) was significantly higher in the BEL+SoC group than in the SoC group. In the BEL+SoC group, low SELENA-SLEDAI score and low GC dose at baseline were associated with being GC dose-tapering discontinuation.ConclusionThe present study suggests that BEL is suitable for patients with SLE during maintenance therapy.

Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort

BackgroundBelimumab was recently approved for treatment of lupus glomerulonephritis (LN). AimTo evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methodsWe considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression. ResultsAmong the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0–47.0) years, median follow-up 22.0 (12.0–36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09–0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95–0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19–0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21–31.7], p = 0.029; 19.8 [2.01–186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28–63.6]; 11.7 [2.7–48.7], p = 0.001 for both). ConclusionsAdd-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.

Long-term open-label continuation study of the safety and efficacy of belimumab for up to 7 years in patients with systemic lupus erythematosus from Japan and South Korea

ObjectivesTo evaluate the long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus (SLE) from Japan and South Korea.MethodsIn this phase III, open-label continuation study (BEL114333; NCT01597622), eligible...

Systematic review of safety and efficacy of belimumab in treating immune-mediated disorders.

Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell-activating factor (BAFF). To evaluate belimumab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist guided the reporting of the data. We searched the PubMed database between October 4, 2016, and June 23, 2019, concentrating on immune-mediated disorders. The literature search identified 583 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 17 articles were finally included in a narrative synthesis. Belimumab is both safe and effective for the treatment of systemic lupus erythematosus. Results were further promising for the use of belimumab in patients with rheumatoid arthritis and Sjögren's syndrome. Conversely, results using belimumab in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and myasthenia gravis were rather disappointing.

PSY11 Belimumab in Patients with Systemic LUPUS Erythematosus in Kazakhstan: A Cost-Effectiveness Analysis

To estimate the cost-effectiveness of belimumab in patients with active, autobody-positive systemic lupus erythematosus (SLE) from the healthcare system perspective of Kazakhstan. The analysis compared current standard of care therapy (SoC) versus SoC plus belimumab (400 mg and 120 mg vials). A microsimulation model with yearly cycles and a lifetime horizon was adapted to the Kazakhstan setting. Data from the BLISS studies was used to inform the model’s clinical and utility parameters. Direct costs were applied using national reference prices and Diagnosis-Related Group tariffs. Probabilistic sensitivity analysis (PSA) was conducted to explore the effect of parameter uncertainty. In the base case scenario, SoC therapy resulted in costs of 16.91 million Kazakhstani tenge (T) (equivalent to 124 589 international dollars (Int$) using the 2019 PPP conversion factor) and 15.14 quality-adjusted life years (QALY), while the corresponding results for SoC plus belimumab amounted to 15.67 QALYs and 28.55 million T (210 390 Int$) for the 400 mg vial or 28.64 million T (211 042 Int$) for the 120 mg vial. The resulting incremental cost-utility ratio was 21.86 million T (161 044 Int$) per QALY gained for the 400 mg vial and 22.02 million T (162267 Int$) for the 200 mg vial. PSA results indicated that the SoC plus belimumab strategy was cost-effective in approximately one-third of iterations at the willingness-to-pay threshold constructed as 3 times national GDP per capita (10.15 million T). In the context of the healthcare system of Kazakhstan, the analysis suggests that the addition of belimumab may potentially improve the outcomes for patients with SLE. Due to the model assumptions and complexity, the results should be interpreted with caution. Additional country-specific data may be needed to more accurately reflect the potential outcomes in patients with SLE in Kazakhstan and the economic impact of belimumab.

Sequential therapy with rituximab and belimumab in patients with systemic lupus erythematosus

Objective: to determine the efficiency of sequential (combined) therapy with rituximab (RTM) and belimumab (BLM) in patients with active systemic lupus erythematosus (SLE).Patients and methods. Twelve patients with true SLE having moderate-to-high activity were followed up. Six of them were noted to have skin and articular manifestations and 6 had kidney damage, vasculitis. The patients took RTM at 500–2000-mg doses, with 6-methylprednisolone as premedication, whereupon they were prescribed BLM according to the standard regimen of 10 mg/kg once monthly. The follow-up period was 1 year. At baseline and every three months after RTM administration, the efficiency and tolerability of therapy were evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded.Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued.evaluated, the concentrations of autoantibodies and complement components was estimated, and the dose of oral glucocorticoids (GCs) was recorded. Results and discussion. During combined therapy with the biological agents (BAs), there was a considerable clinical and laboratory improvement: reductions in disease activity (median (Me) SLEDAI-2K scores were 12 [9.5; 17] at baseline and 2 [2; 6] at Visit 4), the Me concentrations of anti-double-stranded DNA (anti-ds-DNA) antibodies, 101 [39; 250] and 28 [6; 112] U/ml, respectively; those of complement component 3 (C3), 0.44 [0.39; 0.59] and 0.83 [0.81; 0.87] g/L, respectively; and those of complement C4, 0.06 [0.031; 0.1] and 0.16 [0.15; 0.18] g/l, respectively). Most patients received the medium and low doses of oral GCs as initiating therapy. During the year, the dose of GCs was reduced by more than a quarter and they could be completely discontinued. Conclusion. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.. Combined biological therapy with RTM and BLM is a promising treatment for active SLE. The use of this regimen promotes a rapid and effective reduction in disease activity, normalization of laboratory markers of SLE (anti-ds-DNA antibody and complement C3 and C4 levels), and decreases in the dose of oral GCs and, as a consequence, in the risk of irreversible organ damages.

Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: A pilot study

ObjectiveTo report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV). MethodsBelimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded. ResultsAll patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients. ConclusionBelimumab along with rituximab showed promising results in refractory patients with CV.

Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting.

To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Efficacy of belimumab in Primary Sjögren's syndrome: A systematic review.

To evaluate the efficacy and safety of belimumab in patients with Primary Sjögren's syndrome (pSS). The search included manuscripts assessing the efficacy or safety of belimumab in patients with pSS (American-European Consensus Criteria 2002) published between 2004 and 2017 in MEDLINE, EMBASE or Cochrane databases. Two reviewers independently selected the articles, extracted data and evaluated the quality of the evidence following Scottish Intercollegiate Guidelines Network (SIGN) recommendation grades. Out of 135 citations, only 3 articles were included. All of them publishing results from the same study at different time points including 28 patients. At week 28 improvement was reported for visual analogue scale (VAS) dryness score and glandular manifestations in 37% and 77% of patients, respectively, which persisted at week 52 (W52). Belimumab was well tolerated and safely administered. Published evidence to determine the efficacy of belimumab in pSS is limited. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, lymphadenopathies, articular manifestation and B cell biomarkers.

Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus.

We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-α2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5–54.9 pg/mL) versus baseline (28.4; 20.9–100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9–16.1 pg/mL) decreased from month 6 (0.5; 0.5–6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6–9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20–5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-α2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome.

Effectiveness and safety of belimumab in patients with systemic lupus erythematosus in a real-world setting

Objective: To investigate the effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a real-life setting.Methods: All SLE patients treated with belimumab in the Department of Autoimmune Diseases of the Hospital Clinic of Barcelona were retrospectively analysed. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, clinical SLEDAI-2K, levels of anti-double-stranded DNA (anti-dsDNA) antibody, complement components C3 and C4, and 50% haemolytic complement activity (CH50) were recorded at baseline and at 6, 12, and 24 months. Adverse events were also collected.Results: Twenty-three patients (100% women) were enrolled in the study. The most frequent manifestations that led to belimumab use were arthritis (91%) and skin involvement (39%). Both SLEDAI-2K and clinical SLEDAI-2K improved over time at all time-points (p < 0.005). Complement levels increased and the values of anti-dsDNA antibody decreased during treatment. The mean dose of prednisone could be tapered at all time-points and achieved maximum and significant reduction at 24 months (10.4 ± 4.8 mg/day to 4.8 ± 2.1 mg/day; p < 0.0005). Belimumab was well tolerated and only six patients (26%) experienced adverse events, all of which were classified as infections (one urinary tract infection without bacterial detection in urine culture and five viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were noted.Conclusion: In our patients with SLE, belimumab decreased disease activity and allowed tapering of the daily glucocorticoid dose with a good safety profile.

Development and Validation of a Novel Evidence-Based Lupus Multivariable Outcome Score for Clinical Trials.

Trials of new systemic lupus erythematosus (SLE) treatments are hampered by the lack of effective outcome measures. To address this, we developed a novel Lupus Multivariable Outcome Score (LuMOS) and assessed its performance using data from 2 randomized controlled trials of belimumab in patients with SLE. The LuMOS formula was developed by analyzing raw data from 2 pivotal trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76-week (BLISS-76) trials, which are the basis for approval of belimumab. Using the BLISS-76 trial data as the learning data set, we carried out multivariable logistic regression analyses to optimize discrimination of outcomes between patients treated with 10 mg/kg belimumab and patients receiving placebo over the first 52 weeks of follow-up. In addition, the performance of LuMOS was assessed using an independent validation data set from the BLISS-52 trial. The LuMOS model incorporated the following response criteria: a ≥4-point reduction on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, an increase in C4 levels, a decrease in anti-double-stranded DNA titers, and changes in the British Isles Lupus Assessment Group scores for organ system manifestations (no worsening in renal components, and improvements in mucocutaneous components). A decrease in the prednisone dose and increase in C3 levels had very minor impacts on the total LuMOS score. In all analyses of the BLISS-76 and BLISS-52 trial data sets, the mean LuMOS scores were significantly higher (P < 0.0001) in patients treated with 1 mg or 10 mg belimumab compared to placebo. In contrast to the performance of the SLE Responder Index 4 (SRI-4), the LuMOS revealed significant differences between the active treatment group (1 mg belimumab in the BLISS-76 cohort) and placebo group. The effect sizes were significantly much higher with the LuMOS than with the SRI-4. The evidenced-based LuMOS outcome scoring system, developed with data from the BLISS-76 trial of belimumab in patients with SLE and validated with data from the BLISS-52 trial, exhibits a superior capacity to discriminate responders from nonresponders when compared to the SRI-4. Use of the LuMOS may improve the efficiency and power of analyses in future lupus trials.

Correction to: Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies

Correction to: Effectiveness, Tolerability, and Safety of Belimumab in Patients with Refractory SLE: a Review of Observational Clinical-Practice-Based Studies

A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study...

Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial.

To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF). In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression. In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group. Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.

Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study

ObjectiveTo investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. Patients and methodsData of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. ResultsWe studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. ConclusionBelimumab is effective and safe when used in clinical practice setting.

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty‐Two–Week Randomized, Double‐Blind, Placebo‐Controlled Study

ObjectiveTo assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).MethodsPatients with moderate‐to‐severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Secondary end points were reduction in the corticosteroid dosage and time to severe flare. Safety was assessed according to the adverse events (AEs) reported and the laboratory test results.ResultsOf 839 patients randomized, 836 (556 in the belimumab group and 280 in the placebo group) received treatment. A total of 159 patients withdrew before the end of the study. At entry, mean SELENA–SLEDAI scores were 10.5 in the belimumab group and 10.3 in the placebo group. More patients who received belimumab were SRI4 responders than those who received placebo (61.4% versus 48.4%; odds ratio [OR] 1.68 [95% confidence interval (95% CI) 1.25–2.25]; P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171.0 days versus 118.0 days; hazard ratio 0.51 [95% CI 0.35–0.74]; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40–52 (18.2% versus 11.9%; OR 1.65 [95% CI 0.95–2.84]; P = 0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported by 10.8% of patients taking belimumab and 15.7% of those taking placebo. A worsening of IgG hypoglobulinemia by ≥2 grades occurred in 0.9% of patients taking belimumab and 1.4% of those taking placebo.ConclusionIn patients with moderate‐to‐severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.

Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus

Objective: To study self-administration and pharmacokinetics (PK) of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE). Methods: Patients previously treated with belimumab self-administered belimumab 200 mg SC weekly for 8 weeks using an autoinjector. The primary endpoint was the proportion of patients able to self-administer their first and second dose (weeks 1 and 2) in the clinic. The proportion able to self-administer at weeks 4 and 8 (clinic) and weeks 3, 5, 6, and 7 (home) were secondary endpoints. Belimumab PK, safety, and injection-site pain were assessed. Results: 91/95 patients completed the study (withdrawals: adverse events (AEs): 3; lost to follow-up: 1). 93% were female, and mean (SD) age was 44.8 (12.50) years. The majority (99%, 89/90; no attempt, n = 5) successfully self-administered belimumab SC at weeks 1 and 2 (5 had clinic staff assistance), and 98% (85/87) successfully self-administered at weeks 4 and 8. Home-administration success rates were high (93%, (81/87) at weeks 3, 5, 6, and 7). Week 8 median trough concentration was 113 µg/mL. For patients with a ≤ 1.5-week interval between IV SC administration, week-1 concentrations were higher vs. week 8 (+ 51% median) but within a range observed with IV dosing; those with a ≥ 2.5-week interval had median differences close to 0. AEs and serious AEs were low, with no deaths; pain levels were low and decreased with subsequent injections. Conclusion: Patients with SLE successfully self-administered belimumab SC using a novel autoinjector; the PK profile was stable following a switch from IV with acceptable AE and pain levels. The recommended dosing interval between IV to SC dosing is 1 – 4 weeks.

RESULTS OF AN OBSERVATIONAL PROSPECTIVE STUDY OF THE EFFICACY AND SAFETY OF BELIMUMAB (BENLYSTA®) IN SYSTEMIC LUPUS ERYTHEMATOSUS IN REAL CLINICAL PRACTICE

Therapy for systemic lupus erythematosus (SLE) remains challenging. The long-term use of glucocorticoids (GC) and cytostatics considerably improves life expectancy, but at the same time favors the development of irreversible organ damages. To evaluate the efficacy of belimumab (BLM), a biological agent, that blocks B-lymphocyte-stimulating factor registered for the treatment of active SLE, is an important task of the practice of rheumatology. Objective: to evaluate the efficacy and safety of BLM in patients with high and moderate SLE activity. Subjects and methods. The investigation enrolled 16 patients with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score of 6 to 19, who were positive for antinuclear factor (100%) and had low complement levels and high anti-native DNA antibodies (81%). BLM was used as monthly intravenous infusions at a dose of 10 mg/kg. The efficiency and safety of the therapy were evaluated monthly and 1 year after the initiation of treatment with BLM; SLE activity was estimated using SLEDAI-2K; a physician’s global assessment of disease activity on a visual analogue scale (VAS); anti-DNA antibody level changes, complement levels, a GC dose, damage index, and adverse events were determined. Results and discussion. BLM therapy proved to be effective in 62% of cases at 1 year after therapy initiation. At 1 month, SLE activity significantly decreased with SLEDAI-2K score diminishment from 9.31±3.21 to 6.25±2.80 in the entire group (p < 0.04). Over a month, the physician’s global assessment of disease activity significantly reduced from 19.25±6.60 to 13.68±3.97 mm (р<0.01) and reached minimum (8.28±6.87 mm) by 10 months of therapy. There was a significant decrease in anti-DNA antibodies and an increase in complement C4 level at 5 and 3 months of therapy, respectively. Six of the 10 patients who had received a complete cycle of BLM therapy achieved remission at 12 months. The dose of GC was significantly reduced at 6 months of therapy. Adverse events were rare. BLM was discontinued because of its inadequate efficacy in 4 patients. Conclusion. Twelve-month therapy with BLM is effective in patients with high and moderate SLE activity according to SLEDAI-2K and with high immunological activity. The use of BLM in SLE contributes to a GC dose reduction and fails to cause serious adverse events.

Cost-effectiveness analysis of Belimumab in patients with systemic lupus erythematosus in Spain

To estimate the cost-effectiveness of belimumab in patients with systemic lupus erythematosus (SLE) presenting positive biomarkers and active disease despite standard treatment (ST), from the Spanish social perspective. A microsimulation model was used to estimate the cost-effectiveness of belimumab plus ST versus ST alone. A treatment duration of two years with a life-time horizon were considered. Efficacy data were obtained from belimumab clinical trials and the evolution of the disease was simulated from John Hopkins ´ patient cohort data in the United States. Utility data were obtained from literature review. Direct and indirect costs were calculated based on Spanish published data (€, 2014), applying a discount rate (DR) of 3% to both costs and effects. Results were expressed as incremental cost-effectiveness ratio (ICER) in terms of gained life years (LY) and quality of life adjusted life years (QALYs). Probabilistic (PSA) and deterministic sensitivity analyses (DR of 0% and 5%, 5-years treatment duration and excluding indirect costs) were performed to determine the robustness of the model. The incremental cost-effectiveness ratio (ICER) was 16,647€ per life year gained, with an incremental cost-utility ratio (ICUR) of 23,158€ per additional QALY gained. In 68% of the scenarios simulated in the PSA, belimumab was found to be a cost-effective alternative, considering a threshold of 30,000€/ QALY. Belimumab can be regarded as a cost-effective alternative from the Spanish social perspective.